Figures
- FIGURE 1
Patient selection. #: patients excluded due to overlap between studies: 37 from Mathai et al. [17] (25 overlapping cases with Forfia et al. [14] and 12 overlapping cases with Mukherjee et al. [19]) and nine from Ghio et al. [15] which overlapped with Ghio et al. [16]; ¶: from Forfia et al. [14]; +: patients excluded due to incomplete echocardiographic data to be classified according to the four groups: 74 with unavailable data on inferior vena cava, 12 with unavailable tricuspid annular plane systolic excursion and three with unavailable tricuspid regurgitation grade. WHO: World Health Organization; PH: pulmonary hypertension; PAH: pulmonary arterial hypertension.
- FIGURE 2
Spline curve for tricuspid annular plane systolic excursion (TAPSE) versus hazard ratio of all-cause mortality. Changes in hazard ratio for all-cause mortality across the baseline TAPSE.
- FIGURE 3
Kaplan–Meier curves for survival according to a) four and b) three echocardiographic-based risk groups in patients with pulmonary arterial hypertension. The Kaplan–Meier curves show significantly lower 5-year survival rates for high-risk patients (group 4) compared to both intermediate-risk (groups 2 and 3) (43% versus 63%, respectively; p<0.001) and low-risk (group 1) (43% versus 82%, respectively; p<0.001). TAPSE: tricuspid annular plane systolic excursion; TR: tricuspid regurgitation; IVC: inferior vena cava.
- FIGURE 4
Echocardiographic risk stratification in patients with pulmonary arterial hypertension. Three risk categories were identified from four groups representing progressively increasing degrees of right heart dysfunction based upon presence/absence of right ventricular (RV) dysfunction and of systemic venous congestion: a) low risk: preserved tricuspid annular plane systolic excursion (TAPSE) and nonsignificant tricuspid regurgitation (TR) (group 1); b) intermediate risk: either preserved TAPSE and significant TR (group 2) or impaired TAPSE and nondilated inferior vena cava (IVC) (group 3); and c) high risk: impaired TAPSE and dilated IVC (group 4).
Tables
- TABLE 1
General characteristics of publications included in the analysis
First author, year [ref.] Retrospective or prospective design Incident/prevalent PAH patients# Follow-up Outcome measurement Forfia, 2006 [14] Prospective 15/32 19.3 months All-cause mortality Ghio, 2010 [15] Prospective 45/5 52 months All-cause mortality and lung transplantation Mathai, 2011 [17] Prospective 6/7 15.7 months All-cause mortality and lung transplantation Ghio, 2016 [16] Retrospective 33/48 36 months All-cause mortality and lung transplantation Mazurek, 2017 [18] Prospective 0/70 456 days All-cause mortality Mukherjee, 2017 [19] Prospective 17/38 95 months All-cause mortality Tello, 2018 [20] Retrospective 0/290 72.5 months All-cause mortality Data are presented as n/n or median. PAH: pulmonary arterial hypertension. #: overlapping cases were not considered.
- TABLE 2
Characteristic of the overall population and of the four pathophysiologically defined echocardiographic risk groups
Overall population Group 1 Group 2 Group 3 Group 4 p-value Subjects 517 129 155 101 132 Age years 52±15 52±14 53±14 51±17 51±17 0.598 Female 316 (64.8) 67 (57) 102 (70) 68 (68) 79 (64) 0.140 Heart rate bpm 78±14 74±13 76±14 80±15 80±13 0.004 SBP mmHg 123±19 124±17 121±15 123±26 125±18 0.832 DBP mmHg 72±11 74±11 68±9 71±11 74±13 0.109 PAH aetiology Idiopathic 285 (64.8) 75 (65) 85 (59) 50 (70) 75 (68) 0.057 Congenital heart disease 37 (8.4) 7 (6) 12 (8) 10 (14) 8 (7) Portal hypertension 22 (5.0) 9 (8) 10 (7) 1 (1) 2 (2) HIV 12 (2.7) 3 (3) 7 (5) 1 (1) 1 (1) PVOD 11 (2.5) 2 (2) 4 (3) 3 (4) 2 (2) Scleroderma 39 (8.9) 5 (4) 18 (13) 5 (7) 11 (10) Connective tissue disease 23 (5.2) 10 (9) 4 (3) 1 (2) 8 (7) Other 11 (2.5) 4 (4) 4 (3) 0 (0) 3 (3) Prevalent patients 421 (81.4) 118 (92) 137 (88) 75 (74) 91 (69) <0.001 WHO FC III-IV 339 (66.1) 63 (49) 103 (67) 66 (66) 107 (81) <0.001 6MWD m 358±131 405±107 353±128 351±137 317±144 0.007 Vasoactive therapy PDE5i 287 (58.2) 74 (58) 91 (61) 51 (56) 71(57) 0.896 sGC 10 (2.7) 3 (4) 2 (2) 5 (5) 0 (0) 0.121 ERA 240 (48.7) 64 (50) 83 (55) 36 (40) 47 (46) 0.105 Prostanoids 122 (23.6) 31 (24) 41 (27) 20 (20) 30 (23) 0.670 Monotherapy 160 (32.4) 45 (35) 52 (34) 32 (35) 31 (25) 0.246 Combination therapy 215 (43.5) 55 (43) 71 (47) 34 (37) 55 (44) 0.531 Centre location Europe 375 (72.7) 86 (67) 100 (64) 92 (91) 98 (74) <0.001 USA 141 (27.3) 43 (33) 55 (36) 9 (9) 34 (26) Echocardiographic data RVEDD mm 38 (30–45) 32 (5–40) 37 (28–47) 38 (34–46) 42 (34–49) <0.001 RVEDA cm2 29±9 25±7 28±10 28±9 33±8 <0.001 FAC % 27.1±12.2 30±10 30±12 26±10 23±14 0.001 TAPSE mm 18±5 22±4 22±4 14±2 13±3 <0.001 TR moderate to severe 333 (65.0) 0 (0) 155 (100) 66 (67) 112 (87) <0.001 Dilated IVC 196 (44.0) 25 (26) 39 (34) 0 (0) 132 (100) <0.001 PASP mmHg 68±26 50±22 71±28 73±23 77±21 <0.001 AcT ms 78±22 88±23 81±20 71±19 69±18 <0.001 RA area# cm2 21 (17–26) 19 (15–23) 20 (17–24) 20 (16–25) 29 (24–36) <0.001 Pericardial effusion¶ % 32 (27.6) 7 (35) 9 (24) 4 (25) 12 (29) 0.822 LVEDV mL 65 (50–81) 80 (63–95) 70 (62–90) 64 (47–80) 54 (43–67) <0.001 LVEF % 68±12 69±12 68±11 68±13 65±12 0.016 Year of study publication 2006–2011 % 71 (13.7) 18 (14) 19 (12) 9 (9) 25 (19) 0.152 2016–2018 % 446 (86.3) 111 (86) 136 (88) 92 (91) 107 (81) Patient enrolment Prospective % 187 (36.2) 50 (39) 60 (39) 18 (18) 59 (45) <0.001 Retrospective % 330 (63.8) 79 (61) 95 (61) 83 (82) 73 (55) Data are presented as n, mean±sd, n (%) or median (interquartile range), unless otherwise stated. All percentages are calculated based on data availability for each parameter. SBP: systolic blood pressure; DBP: diastolic blood pressure; PAH: pulmonary arterial hypertension; PVOD: pulmonary veno-occlusive disease; WHO FC: World Health Organization functional class; 6MWD: 6-min walk distance; PDE5i: phosphodiesterase-5 inhibitor; sGC: soluble guanylate cyclase stimulator; ERA: endothelin receptor antagonist; RVEDD: right ventricular end-diastolic diameter; RVEDA: right ventricular end-diastolic area; FAC: fractional area change; TAPSE: tricuspid annular plane systolic excursion; TR: tricuspid regurgitation; IVC: inferior vena cava; PASP: pulmonary arterial systolic pressure; AcT: acceleration time; RA: right atrial; LVEDV: left ventricular end-diastolic volume; LVEF: left ventricular ejection fraction. #: data available for 314 patients; ¶: data available for 116 patients.
- TABLE 3
Univariable and multivariable Cox regression analysis
Univariate analysis HR (95% CI) p-value Multivariate analysis HR (95% CI) p-value Age 1.02 (1.01–1.03) <0.001 1.02 (1.01–1.03) <0.001 Female sex 0.71 (0.53–0.94) 0.017 0.69 (0.51–0.94) 0.019 Heart rate 1.02 (1.01–1.03) 0.002 PVOD# 5.00 (2.50–10.00) <0.001 Scleroderma PAH# 1.50 (0.90–2.50) 0.121 Connective tissue disease PAH# 2.80 (1.49–5.26) 0.001 Incident PAH¶ 1.67 (1.16–2.41) 0.006 1.06 (0.61–1.84) 0.831 Combination therapy+ 1.16 (0.88–1.54) 0.293 Study published in 2016–18§ 0.55 (0.36–0.83) 0.005 0.53 (0.27–1.03) 0.060 Data from retrospective studyƒ 0.90 (0.66–1.21) 0.484 WHO FC III–IV 2.96 (2.02–4.34) <0.001 2.46 (1.61–3.75) <0.001 6MWD per 10-m increase 0.96 (0.94–0.98) <0.001 Centre location in USA 0.83 (0.60–1.18) 0.301 TAPSE## 0.92 (0.89–0.94) <0.001 TAPSE ≤17 mm 2.37 (1.78–3.14) <0.001 RVEDD 1.01 (1.00–1.02) 0.076 RVEDA 1.05 (1.02–1.07) <0.001 FAC 0.97 (0.95–0.99) 0.008 AcT 0.98 (0.97–0.99) <0.001 PASP 1.01 (1.00–1.01) 0.006 RA area 1.04 (1.02–1.06) <0.001 Pericardial effusion 1.33 (0.69–2.59) 0.396 Dilated IVC 2.12 (1.57–2.86) <0.001 TR moderate to severe 2.00 (1.43–2.79) <0.001 LVEDV 0.99 (0.97–0.99) 0.005 LVEF 0.98 (0.97–0.99) 0.002 0.99 (0.98–1.01) 0.230 Intermediate¶¶ versus low risk++ 2.15 (1.38–3.37) 0.001 2.51 (1.46–4.29) 0.001 High§§ versus low risk++ 4.54 (2.88–7.15) <0.001 4.37 (2.52–7.59) <0.001 HR: hazard ratio; PVOD: pulmonary veno-occlusive disease; PAH: pulmonary arterial hypertension; WHO FC: World Health Organization functional class; 6MWD: 6-min walk distance; TAPSE: tricuspid annular plane systolic excursion; RVEDD: right ventricular end-diastolic diameter; RVEDA: right ventricular end-diastolic area; FAC: fractional area change; AcT: acceleration time; PASP: pulmonary arterial systolic pressure; RA: right atrial; ICV: inferior vena cava; TR: tricuspid regurgitation; LVEDV: left ventricular end-diastolic volume; LVEF: left ventricular ejection fraction. #: versus idiopathic PAH; ¶: versus prevalent PAH; +: versus monotherapy or no specific therapy; §: versus 2006–2011; ƒ: versus prospective study; ##: as a continuous variable; ¶¶: groups 2 and 3; ++: group 1; §§: group 4.
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