A novel scoring index by Doppler echocardiography for predicting severe pulmonary hypertension due to chronic lung diseases: a cross-sectional diagnostic accuracy study

Figures & data

Table 1 Demographic characteristics, pulmonary function test results, hemodynamics, and echocardiography parameters of patients with normal/PH vs severe PH

Variable	Normal/PH (n=51)	Severe PH (n=56)	P-value
Age (years)	64.0 (57.5, 70.5)	61.0 (48.0, 67.8)	0.059
Men	30 (66.7%)	37 (61.7%)	0.638
BSA (m^2)	1.6±0.2	1.6±0.2	0.543
Diagnosis
COPD	35 (68.6%)	40 (71.4%)	0.753
Interstitial lung disease	4 (7.8%)	6 (10.7%)	0.612
Other diseases with mixed restrictive and obstructive pattern
Combined pulmonary fibrosis and emphysema	1 (2.0%)	1 (1.8%)	0.947
Lobectomia pulmonalis	3 (5.9%)	1 (1.8%)	0.267
Chest deformity	1 (2.0%)	1 (1.8%)	0.947
Lung destruction due to tuberculosis	3 (5.9%)	2 (3.6%)	0.573
Bronchiectasis	1 (2.0%)	3 (5.4%)	0.357
Pneumoconiosis	1 (2.0%)	0 (1.7%)	0.295
Sleep-disordered breathing	1 (2.0%)	2 (3.6%)	0.616
Alveolar hypoventilation disorders	1 (2.0%)	0	0.295
Comorbidities
Systemic hypertension	10 (22.2%)	10 (16.7%)	0.616
Diabetes mellitus	3 (6.7%)	1 (1.7%)	0.311
Coronary heart disease	4 (8.9%)	1 (1.7%)	0.162
Malignant tumor	0	1 (1.7%)	0.386
Arrhythmia	6 (13.3%)	4 (6.7%)	0.320
Hyperlipidemia	3 (6.7%)	0	0.076
Previous cerebral infarction	0	1 (1.7%)	0.386
Pulmonary function test
FEV1 % predicted	48.8±23.3	48.5±21.0	0.309
FVC % predicted	67.5±25.4	62.0±20.7	0.664
FEV1/FVC % predicted	57.7±18.2	61.9±16.1	0.409
RV % predicted	178.9±62.9	156.3±55.3	0.178
TLC % predicted	109.5±27.4	101.2±19.6	0.197
DLco % predicted	51.4±27.4	57.6±33.9	0.471
Hemodynamics
mRAP (mmHg)	4.0 (2.0, 5.0)	7.0 (4.0, 9.0)	<0.001
mPAP (mmHg)	29.0 (24.5, 32.0)	47.0 (41.0, 57.5)	<0.001
PAWP (mmHg)	8.1±3.4	9.9±4.3	0.022
CO (L/min)	5.7 (4.3, 6.6)	4.7 (4.0, 5.7)	0.034
Cardiac index (L/min/m^2)	3.5±0.8	3.2±1.0	0.192
PVR (Wood units)	3.6 (2.4, 4.8)	7.9 (6.2, 10.2)	<0.001
Echocardiography
LVEF (%)	69.1±7.6	71.3±9.3	0.186
RATD (cm)	4.0 (3.5, 4.7)	4.8 (3.2, 5.5)	<0.001
RALD (cm)	4.5 (3.9, 5.4)	5.2 (4.5, 6.0)	0.005
RVEDTD (cm)	3.5 (3.1, 3.9)	4.3 (3.8, 5.0)	<0.001
RVEDLD (cm)	5.8 (5.5, 6.7)	6.5 (5.8, 7.1)	0.011
PASP (mmHg)	47.4±11.6	76.0±21.9	<0.001
TAPSE (cm)	2.0±0.3	1.7±0.3	<0.001
PAd (cm)	2.4 (2.2, 2.7)	2.8 (2.6, 3.2)	<0.001
ENDSEI	1.0 (1.0, 1.1)	1.3 (1.1, 1.5)	<0.001
PASP – yes	41 (80.4%)	52 (92.9%)	0.057

Note: Data shown as mean ± SD, n (%) or median (quartile range).

Abbreviations: PH, pulmonary hypertension; BSA, body surface area; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; RV, residual volume; TLC, total lung capacity; DLco, diffusing capacity for carbon monoxide; mRAP, mean right atrium pressure; mPAP, mean pulmonary artery pressure; PAWP, pulmonary artery wedge pressure; CO, cardiac output; PVR, pulmonary vascular resistance; LVEF, left ventricular ejection fraction; RATD, right atrial transverse dimension; RALD, right atrial longitudinal dimension; RVEDTD, right ventricular end-diastolic transverse dimension; RVEDLD, right ventricular end-diastolic longitudinal dimension; PASP, pulmonary arterial systolic pressure; TAPSE, tricuspid annular plane systolic excursion; PAd, pulmonary artery diameter; ENDSEI, end-systolic-stage eccentricity index.

Figure 1 Flow diagram for the main derivation cohort. Of the 369 patients with CLD and suspected PH who were referred to the Cardio-Pulmonary Circulation Center of Shanghai Pulmonary Hospital within the study period, 107 met the inclusion criteria and were considered in the analysis.

Abbreviations: CLD, chronic lung disease; PH, pulmonary hypertension; RHC, right heart catheterization; DE, Doppler echocardiography.

Table 2 Logistic regression analysis of echocardiography parameters associated with severe PH

Variable*	Univariate analysis		β-coefficient	Weighted scores	Multivariate analysis
	OR (95% CI)	P-value			OR (95% CI)	P-value
RATD (cm)	5.249 (2.262, 12.389)	<0.001	–	–	–	–
RALD (cm)	4.491 (2.138, 11.418)	<0.001	–	–	–	–
RVEDTD (cm)	10.771 (4.311, 26.909)	<0.001	1.665	2†	5.283 (1.368, 20.403)	0.016
RVEDLD (cm)	3.229 (1.426, 7.313)	0.005	–	–	–	–
PASP (mmHg)	23.688 (8.383, 66.940)	<0.001	2.981	3†	19.710 (5.032, 77.206)	<0.001
PAd (cm)	6.889 (2.789, 17.015)	<0.001	1.941	2†	6.963 (1.803, 26.893)	0.005
ENDSEI	16.593 (4.621, 59.581)	<0.001	–	–	–	–
TAPSE (cm)	0.168 (0.058, 0.488)	0.001	−2.864	−3†	0.057 (0.010, 0.320)	0.001

Notes:

* Variables were transformed into binary variables according to optimum cutoff values.

† If RVEDTD ≥3.8 cm or PAd ≥2.7 cm, weighted score =+2; if PASP ≥61 mmHg, weighted score =+3; and if TAPSE ≥1.65 cm, weighted score =−3.

Abbreviations: PH, pulmonary hypertension; RATD, right atrial transverse dimension; RALD, right atrial longitudinal dimension; RVEDTD, right ventricular end-diastolic transverse dimension; RVEDLD, right ventricular end-diastolic longitudinal dimension; PASP, pulmonary arterial systolic pressure; PAd, pulmonary artery diameter; ENDSEI, end-systolic-stage eccentricity index; TAPSE, tricuspid annular plane systolic excursion.

Table 3 The distribution of echocardiography parameters and accuracy for discrimination

Variable	All subjects (n=107)	Normal/PH (n=51)	Severe PH (n=56)	P-value	Sensitivity (%)	Specificity (%)	Area under the curve (95% CI)
RATD (cm)
<4.2	46 (43.0)	33 (64.7)	13 (23.2)	<0.001	0.768	0.647	0.707 (0.607, 0.807)
≥4.2	61 (57.0)	18 (35.3)	43 (76.8)
RALD (cm)
<4.8	52 (48.6)	35 (68.6)	17 (30.4)	0.008	0.696	0.686	0.650 (0.543, 0.756)
≥4.8	55 (51.4)	16 (31.4)	39 (69.6)
RVEDTD (cm)
<3.8	47 (43.9)	14 (27.5)	10 (17.9)	<0.001	0.821	0.725	0.801 (0.716, 0.886)
≥3.8	60 (56.1)	37 (72.5)	46 (82.1)
RVEDLD (cm)
<6.4	61 (57.0)	14 (27.5)	11 (19.6)	0.002	0.571	0.725	0.672 (0.569, 0.774)
≥6.4	46 (43.0)	37 (72.5)	45 (80.4)
PASP (mmHg)
<61	54 (50.5)	43 (84.3)	11 (19.6)	<0.001	0.804	0.843	0.869 (0.797, 0.942)
≥61	53 (49.5)	8 (15.7)	45 (80.4)
PAd (cm)
<2.7	57 (53.3)	39 (76.5)	18 (32.1)	<0.001	0.679	0.765	0.745 (0.675, 0.855)
≥2.7	50 (46.7)	12 (23.5)	38 (67.9)
ENDSEI
<1.05	48 (46.9)	35 (68.6)	13 (23.3)	<0.001	0.768	0.683	0.792 (0.706, 0.878)
≥1.05	59 (55.1)	16 (31.4)	43 (76.8)
TAPSE (cm)
<1.65	27 (25.2)	5 (9.8)	22 (39.3)	0.001	0.902	0.607	0.684 (0.584, 0.784)
≥1.65	80 (74.8)	46 (90.2)	34 (60.7)

Note: Data shown as n (%).

Abbreviations: PH, pulmonary hypertension; RATD, right atrial transverse dimension; RALD, right atrial longitudinal dimension; RVEDTD, right ventricular end-diastolic transverse dimension; RVEDLD, right ventricular end-diastolic longitudinal dimension; PASP, pulmonary arterial systolic pressure; PAd, pulmonary artery diameter; ENDSEI, end-systolic-stage eccentricity index; TAPSE, tricuspid annular plane systolic excursion.

Figure 2 The receiver-operator characteristic curve is shown for PASP alone as determined by echocardiography variables and for ESI in predicting severe PH.

Abbreviations: PASP, pulmonary arterial systolic pressure; ESI, echocardiography scoring index; PH, pulmonary hypertension; AUC, area under the curve; DE, Doppler echocardiography.

Figure 3 Representative echocardiographic images of RVEDTD, PASP, PAd, and tricuspid annular plane systolic excursion as well as the score calculation for two patients. Column A (top to bottom) shows ↑RVEDTD and ↑PASP (score =−1). Invasive hemodynamics: mPAP =30 mmHg, PAWP =11 mmHg, PVR =6.0 Wood units, and cardiac index =3.1 L/min/m². Column B shows ↑RVEDTD, ↑PASP, ↑PAd, and ↓TAPSE (score =4). Invasive hemodynamics: mPAP =39 mmHg, PAWP =11 mmHg, PVR =6.0 Wood units, and cardiac index =3.35 L/min/m².

Abbreviations: RVEDTD, right ventricular end-diastolic transverse dimension; PASP, pulmonary arterial systolic pressure; PAd, pulmonary artery diameter; mPAP, mean pulmonary artery pressure; PAWP, pulmonary artery wedge pressure; PVR, pulmonary vascular resistance; TAPSE, tricuspid annular plane systolic excursion; ESI, echocardiography scoring index.

Table S1 Sensitivity, specificity, positive predictive values, and negative predictive values of the diagnostic index

Cutoff values	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
Derivation cohort
Cutoff =1.5	87.5	92.2	92.5	87.0
Cutoff =1.0	91.1	80.4	83.6	89.1
Validation cohort
Cutoff =1.5	64.7	76.9	78.6	62.5
Cutoff =1.0	81.3	84.2	84.2	81.3

Abbreviations: PPV, positive predictive value; NPV, negative predictive value.

Table S2 Comparison of characteristics of patients of derivation cohort vs validation cohort

Variable	Derivation cohort (n=107)	Validation cohort (n=35)	P-value
Age (years)	63.0 (54.0, 70.0)	63.0 (56.5, 68.0)	0.998
Men (%)	67	21	0.458
BSA (m^2)	1.6 (0.2)	1.6 (0.2)	0.204
Diagnosis
COPD	36 (80.0)	27 (90.0)	0.157
ILD	4 (8.9)	3 (10.0)	0.863
Bronchiectasia	10 (22.2)	8 (26.7)	0.962
Other pulmonary diseases with mixed restrictive and obstructive pattern
CPFE	1 (2.2)	1 (3.3)	0.893
Lobectomia pulmonalis	4 (8.9)	0	0.229
Chest deformity	1 (2.2)	1 (6.7)	0.320
Emphysema and bullae	2 (4.4)	4 (13.3)	0.228
Lung destruction due to tuberculosis	3 (6.7)	1 (3.3)	0.286
Pneumoconiosis	1 (2.2)	0	0.452
Sleep-disordered breathing	1 (2.2)	0	0.356
Alveolar hypoventilation disorders	2 (4.4)	0	0.452
Comorbidities
Systemic hypertension	20 (19.0)	7 (23.3)	0.493
Diabetes mellitus	4 (3.9)	2 (6.7)	0.490
Coronary heart disease	4 (4.8)	1 (3.3)	0.420
Malignant tumor	1 (1.0)	1 (3.3)	0.629
Arrhythmia	10 (9.5)	2 (6.7)	0.460
Hyperlipidemia	3 (2.9)	2 (6.7)	0.320
Previous cerebral infarction	1 (1.0)	0	0.596
Pulmonary function test
FEV1 % predicted	32.8 (23.7, 60.4)	33.0 (20.0, 44.3)	0.201
FVC % predicted	53.0 (39.5, 63.3)	56.4 (43.9, 63.0)	0.406
FEV1/FVC % predicted	55.2 (44.5, 69.0)	45.0 (39.7, 67.5)	0.067
RV % predicted	156.9 (106.3, 217.0)	196.4 (108.1, 304.0)	0.237
TLC % predicted	100.5 (80.8, 122.1)	107.2 (78.3, 135.4)	0.461
RV/TLC % predicted	67.2 (53.9, 78.1)	71.1 (51.0, 79.5)	0.681
DLco % predicted	48.9 (26.9, 64.2)	29.6 (23.5, 53.8)	0.128
DLco/VA % predicted	50.8 (27.2, 72.6)	35.4 (23.2, 66.8)	0.292

Note: Data shown as mean (SD) or median (quartile range).

Abbreviations: BSA, body surface area; ILD, interstitial lung disease; CPFE, combined pulmonary fibrosis and emphysema; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; RV, residual volume; TLC, total lung capacity; DLco, diffusing capacity for carbon monoxide; VA, alveolar volume.

Table S3 Comparison of hemodynamics and echocardiography parameters of patients of derivation cohort vs validation cohort

Variable	Derivation cohort (n=107)	Validation cohort (n=35)	P-value
Hemodynamics
mRAP (mmHg)	5.0 (3.0, 8.0)	3.0 (1.0, 5.0)	0.001
mPAP (mmHg)	36.0 (29.0, 48.0)	35.0 (28.5, 42.0)	0.169
PAWP (mmHg)	9.2 (3.8)	8.2 (5.3)	0.188
CO (L/min)	5.0 (4.2, 6.1)	5.0 (4.2, 6.5)	0.716
Cardiac index (L/min/m^2)	3.3 (0.9)	3.2 (0.8)	0.820
PVR (Wood units)	3.6 (3.5, 8.1)	5.0 (3.0, 7.3)	0.484
Echocardiography parameters
Continuous variables
LVEF (%)	70.0 (64.0, 77.0)	70.5 (62.0, 77.3)	0.186
RATD (cm)	4.4 (3.7, 5.3)	4.3 (3.7, 4.6)	0.256
RALD (cm)	4.8 (4.1, 5.7)	4.6 (4.2, 5.2)	0.274
RVEDTD (cm)	3.9 (3.3, 4.5)	3.7 (3.5, 4.2)	0.581
RVEDSD (cm)	6.2 (5.6, 6.8)	6.1 (5.7, 6.9)	0.971
PASP (mmHg)	60.0 (43.0, 76.0)	51.0 (35.0, 65.0)	0.009
TAPSE (cm)	1.8 (1.6, 2.0)	1.8 (1.6, 2.2)	0.940
PAd (cm)	2.6 (2.4, 2.9)	2.8 (2.5, 3.0)	0.103
ENDSEI	1.1 (1.0, 1.3)	1.1 (1.0, 1.3)	0.338
Categorical variables
RH enlargement* – yes	81 (75.7%)	22 (73.3%)	0.792
PA dilation – yes	48 (44.9%)	17 (56.7%)	0.094
ENDSEI – yes	60 (56.1%)	15 (50.0%)	0.556
PASP – yes	93 (86.9%)	17 (56.7%)	<0.001

Notes: Data shown as mean (SD), median (25th, 75th percentiles) or n (%).

* Include right atrium and right ventricle enlargement.

Abbreviations: mRAP, mean right atrium pressure; mPAP, mean pulmonary artery pressure; PAWP, pulmonary artery wedge pressure; CO, cardiac output; PVR, pulmonary vascular resistance; LVEF, left ventricular ejection fraction; RATD, right atrial transverse dimension; RALD, right atrial longitudinal dimension; RVEDTD, right ventricular end-diastolic transverse dimension; RVEDSD, right ventricular end-diastolic dimension; PASP, pulmonary artery systolic pressure; TAPSE, tricuspid annular plane systolic excursion; PAd, pulmonary arterial diameter; ENDSEI, end-systolic eccentricity index; RH, right heart; PA, pulmonary artery.