1. Patrick SK. Liu Shiu Cheong
Relationship of right heart echo parameters to functional status and pulmonary function in severe COPD
Patrick SK. Liu Shiu Cheong
Brian J. Lipworth
Andrew R. Goudie
Pippa J. Hopkinson
Philip M. Short
Allan D. Struthers

2. COPD & Pulmonary circulation
COPD affects the pulmonary circulation.
This diagram summarises these effects on the pulmonary circulation. Eventually COPD causes changes in the cardiac structure and the cardiac function in the presence or absence of pulmonary hypertension.
Minai et al. Chest 2010;137(6)(Suppl):39S-51S

3. What we already know
In COPD-associated PH, invasively measured PAP is independently associated with reduced exercise function in patients with severe COPD1
Most patients with advanced COPD do not typically undergo right heart catheterisation unless clinically indicated (for e.g. patients awaiting lung transplantation)
Sims et al. Chest 2009;136:

4. Echocardiography
Echocardiography remains the most widely used non-invasive diagnostic tool for the assessment of PH due to lung diseases and/or hypoxia (group 3).
Doppler echo
Right Ventricular Systolic Pressure (RVSP)
RVSP = 4 x (TR Vmax)2 + RA pressure in mm Hg
Mean Pulmonary artery pressure (MPAP)
MPAP = 90 – (0.62 x acceleration time) in mm Hg2
Pulmonary vascular resistance (PVR)
PVR = ([TR Vmax (m/s) / RVOTVTI (cm)] x ) in Woods Units3
2015 ESC/ERS guidelines published a few months ago have recommended that echo should always be performed when PH is suspected.
The development of Doppler echo has had significantly impact on clinical medicine. We have been able to determine intracardiac haemodynamics non-invasively.
For example, we can estimate PAP and PVR by studying TR jets and pulmonary flow-velocity waves.
Difficulties to measure RVSP in COPD.
Dabestani et al. Am J Cardio 1987;59:
Abbas et al. JACC 2003;41(6):1021-7

5. Pulsed-wave Doppler Echo at pulmonary valve
This is an example of a pulsed-wave doppler echo trace taken at the pulmonary valve.
We can make 3 measurements on this.
Pulmonary acceleration time – which is measured from the onset of ejection (TV0) to the time of peak flow velocity (TPV)
Right Ventricular ejection time – which is measured from the onset to the end of systolic flow velocity recording.
Right Ventricular Outflow Tract velocity-time intergral – this is the area under the curve of the spectral trace and this can be calculated by the echo machine

6. Aims
To investigate whether measurements made by simple, non-invasive and easily accessible echo are related to quality of life and health status and to pulmonary function in patients with moderate to severe COPD

7. Methods
Post-hoc analysis from database of patients with COPD and PH (Goudie et al. Lancet RM 2014 ) who have had
Echocardiogram
Pulmonary function (spirometry, DLCO)
Functional status (SGRQ, SF-36, 6MWT)
Excluded:
LV systolic dysfunction (LVEF < 45%)

8. Patient Characteristics
No of patients
120
Men
82 (68%)
Mean Age
69 ± 8
Mean BMI
26 ± 5
Mean Sa02
95 ± 3
Mean FEV1 %
41 ± 15
Mean FEV1/FVC
0.38 ± 0.09
Mean FVC %
84.7 ± 20.8
Mean Adj. DLCO %
37.9 ± 13.9
Mild decreased SaO2 at rest.
Severe obstructive spirometric values.
Impaired DLCO suggesting evidence of component of emphysema.

9. Patient Characteristics – Key Echo parameters
Pulmonary Acceleration Time (PAT in ms)
97 ± 11
MPAP = 30 ± 7 mm Hg
Normal PAT ≥ 105ms (= 25 mm Hg)
Right Ventricular Ejection Time (RVET in ms)
272 ± 42
Normal values: 322 ± 21
PVR 2.0 ± 0.7 Wood Units
Normal: PVR < 2
TR Vmax 2.75 ± 0.41
Normal TR Vmax < 2.80 ms-1
Normal values of RVET obtained from Tei et al. paper (Doppler Echocardiographic Index for assessment of global right ventricular function. J Am Soc Echocardiogr 1996)
They studied 26 patients with primary pulmonary hypertension and 37 age-matched normal subjects.
Ejection time shortened significantly in patients with pulmonary hypertension (241 ± 43 ms) vs normal (322 ± 21 ms), p < 0.001
RV systolic dysfunction shortened ejection time.
Ejection time shortened in patients with pulmonary hypertension. It is also shortened with increasing heart rate.
Other contributing factors:
Elevation of pulmonary vascular impedance
Decreased RV filling and decreased stroke volume

10. Echo parameters: correlations 1
Variable r
p Value
RVET
SGRQ
-0.19
0.02
SF-36: General health perceptions
0.18
SF-36: Limitations due to physical problems
0.17
0.03
SF-36: Social functioning
0.16
SF-36: Physical function
0.04
6MWD NS
FEV1 %
0.31
< 0.001
FVC %
0.36
FEV1/FVC
Adj DLCO %
0.28
0.001
When looking at the relationship of right echo parameters and pulmonary haemodynamic measurements with function status and pulmonary function results.
We found statistically significant but not strong correlation between RV ejection time with functional status (including SGRQ, SF-36 scores) and between RVET with pulmonary function measurements (FVC %, FEV1 %, Adj DLCO % and FEV1/FVC).
RVET correlated with Impact score of SGRQ (r = , p = 0.03)

11. Echo parameters: correlations 2
Variable r
p Value
PAT
Adj DLCO %
0.19
0.04
PVR
6MWD
-0.36
0.008
FVC %
-0.30
0.03
Adj. DLCO %
-0.39
0.006
RVSP
-0.31
0.05
For PVR, it was similar. There are statistically significant but weak correlation with functional status and pulmonary function.
PVR 2.0 ± 0.7 Wood Units
Normal: PVR < 0.2
TR Vmax 2.75 ± 0.41
Normal TR Vmax < 2.80 ms-1
After estimating the pulmonary vascular resistance using the equation from the Abbas paper, we found that there were significant correlation between PVR and 6MWD, BODE index, FVC % and Adj. DLCO %
BODE Index: Body mass index, airflow Obstruction (FEV1 %), Dyspnoea (MMRC Dyspnoea scale), Exercise (6MWD)

12. Pulmonary Acceleration Time (PAT & RVET measured in 99% of patients)
PAT < 100 ms
PAT ≥ 100 ms
p Value n 68 51
Mean SGRQ
59.3 (14.9)
52.1 (15.8)
0.01
Mean RVET (ms)
262 (41.9)
286 (38.43)
0.001
When stratifying patients into 2 groups:
PAT of 100 ms = mean PAP of 28 mm Hg
We also found a statistically significant difference in mean SGRQ score and mean RVET.
SGRQ – statistically significant difference in the activity and impact scores for SGRQ
The threshold for a clinically significant difference between groups of patients and for changes within groups of patients is four unit.

13. Dynamic lung volumes & functional status: correlations 1
Pulmonary function
Functional status r
p Value
FEV1 %
SGRQ
-0.28
0.001
SF-36: limitations due to physical problems
0.33
<
SF-36: physical function
0.40
< 0.001
SF-36: social function
0.30
SF-36: general health perceptions
0.39
FVC %
0.25
0.003
0.20
0.02
SF-36: general health perception
0.16
0.04
Moving away from Doppler echo measurement, we found statistically significant correlation between dynamic lung volumes and functional status. This is nothing new and has been showed in previous studies.
As expected, pulmonary function showed significant correlation with quality of life questionnaires (SGRQ and SF-36).

14. Dynamic lung volumes & functional status: correlations 2
Pulmonary function
Functional status r
p Value
FEV1/FVC
SGRQ
-0.25
0.003
SF-36: limitations due to physical problems
0.34
< 0.001
SF-36: physical functioning
0.32
SF-36: social functioning
0.25
SF-36: general health perceptions
0.38
Adj DLCO %
-0.33
0.001
0.42
0.35
SF-36: emotional well-being
0.26
0.002
SF-36: emotional role limitations
0.24
0.004
6MWD
0.20
0.03
We also found statistically significant correlation between degree of obstruction (FEV1/FVC ratio) and functional status, and between transfer factor and functional status.

15. GOLD 2 vs GOLD 4 GOLD 2 GOLD 4 Difference p Value n 30 (25%) 31 (26%)
Mean RVET
279 ± 40
242 ± 39 38
0.001
Mean SF-36 scores for
Physical functioning
38.83 ± 21.88
19.48 ± 19.95
19.35
< 0.001
Limitations due to physical problems
34.17 ± 37.42
9.48 ± 23.54
26.68
0.009
Social functioning
73.33 ± 29.50
50.86 ± 28.92
22.47
0.01
General health perceptions
40.33 ± 22.01
24.66 ± 11.80
15.68
When dividing the patients in groups according to GOLD criteria, we have found significant differences in the mean RVET and mean SF36 scores between GOLD 2 and GOLD 4 groups.
This is expected and validate our database.

16. Summary
Significant but weak correlation between right heart echo parameters and functional status and between right heart echo parameters and pulmonary function
The correlation between pulmonary function and functional status was equally significant and weak.
Using Pulmonary acceleration time of 100 ms may help to predict which patients would have worse functional status (SGRQ score)
As expected, patients in GOLD 4 have worse functional impairment than those in GOLD 2.

17. Limitations Relatively small cohort
Resting echo – i.e. not stress echo or exercise
No serial data over months or years
No data on exacerbations or mortality
No assessment of O2 reversibility
Reliance on resting echo to predict functional status or exercise tolerance may limit our findings. Isolated exercise induced PH is common in COPD.
Presence of isolated exercise induced PH was a predictor of developing resting PH in the 6-year follow up.

18. Conclusion Weak correlations in our cohort
Echo – simple, non-invasive and easily accessible test
Different population
Serial data

19. Acknowledgement Professor Brian Lipworth Professor Allan Struthers
Dr Andrew Goudie
Dr Arvind Manoharan
Dr Philip Short
Mrs Pippa Hopkinson

21. GOLD criteria GOLD 2 GOLD 3 GOLD 4 n 30 (25%) 59 (49%) 31 (26%)
Mean RVET
279 ± 40
283 ± 37
242 ± 39
Mean PAT
94 ± 12
100 ± 12
96 ± 10
6MWD
340 ± 105
334 ± 121
366 ± 85
SGRQ
50.14 ± 17.32
56.80 ± 16.38
59.48 ± 12.86
Mean SF-36 scores for
Physical functioning
38.83 ± 21.88
26.19 ± 19.08
19.48 ± 19.95
Limitations due to physical problems
34.17 ± 37.42
18.22 ± 31.77
9.48 ± 23.54
Social functioning
73.33 ± 29.50
59.32 ± 30.14
50.86 ± 28.92
General health perceptions
40.33 ± 22.01
28.39 ± 14.90
24.66 ± 11.80
When dividing the patients in groups according to GOLD criteria, we have found significant differences in the mean RVET and mean SF36 scores between GOLD 2 and GOLD 4 groups.
This is expected and validate our database.

22. Continuous-wave Doppler Echo for TR
RV systolic pressure in mm Hg = (4 x v2) + RA pressure
This is an example of a continuous-wave doppler trace that we get with TR.
We use the tricuspid regurgitation jet maximum velocity (red arrow) to measure the pressure gradient between the right ventricle and right atrium.
Using the simplified Bernoulli equation and adding the right atrial pressure, we can calculate the RV systolic pressure, which equals the systolic pulmonary artery pressure (in absence of a gradient across the pulmonary valve).
RA pressure is estimated by IVC diameter and presence of inspiratory collapse

23. Echo views for measurement of the TR jet
Echo views for measurement of the TR jet. Ensure that TR jet is parallel to the U/S beam.

24. Echo views for measurement of the pulmonary acceleration time.

25. Mean PAP = 90 – (0.62 x acceleration time) in mm Hg
39 patients had right heart catheterisation and pulsed doppler echo
Negative correlation with mean PAP
r = -0.87, p < 0.001

26. PVR = ([TR Vmax (m/s) / RVOTVTI (cm)] x 10 + 0.16) in Woods Units
44 patients had doppler measurements and invasive measurements (pulmonary artery catheter)
r = 0.93, p <
We can calculate the PVR by using the equation from Abbas et al. study which had a statistically significant Pearson correlation coefficient of 0.9 when Doppler measurements were analysed with invasive pulmonary artery catheterisation measurements.
PVR can be calculated by dividing the pressure difference across the pulmonary circuit by the transpulmonary flow. By using the peak tricuspid regurgitation velocity as a surrogate for pressure and the VTI of the right ventricular outflow tract as a surrogate of flow, PVR can be estimated from the equation as described from Abbas et al. study.

27. Calculating SPAP / RVSP
Simplified Bernoulli equation:
RVSP = 4v2 + RA pressure in mm Hg
where v = TR Vmax,
RA pressure is estimated by IVC diameter and presence of inspiratory collapse
We use the tricuspid regurgitation jet maximum velocity (red arrow) to measure the pressure gradient between the right ventricle and right atrium.
Using the simplified Bernoulli equation and adding the right atrial pressure, we can calculate the RV systolic pressure, which equals the systolic pulmonary artery pressure (in absence of a gradient across the pulmonary valve).
RA pressure is estimated by IVC diameter and presence of inspiratory collapse

28. Other Echo Measurements
Abnormal range
% of patients
RVD1 (Basal RV diameter)
> 4.2 cm
1.4%
RVD2 (Mid RV diameter)
> 3.5 cm
12.7%
RVD3 (Base to apex length)
> 8.6 cm
RVH
RV wall > 5 mm
78%
LVIDd 1%
LVIDd > 5.3 cm in female
LVIDd > 5.9 cm in male