Kozu et al., Page 1 Online data supplement. Current status of long-term prognosis among all subtypes of pulmonary hypertension in Japan Katsuya Kozu, Koichiro Sugimura, Masaaki Ito, Ken-ichi Hirata, Koichi Node, Takuya Miyamoto, Shuichi Ueno, Hiroshi Watanabe, Hiroaki Shimokawa; for the Japanese Pulmonary Circulation Study Group Table of contents Supplementary Table S1. Baseline patient characteristics of PAH and PVOD.............................................Page 2 Supplementary Table S2. Baseline patient characteristics of PAH by maximum medication reached during follow- up......................................................................... ........................................................................... ......Page 4 Supplementary Table S3. Cox proportional hazards models of baseline variables in PAH..........................Page 6 Supplementary Table S4. Cox proportional hazards models of eGFR in PAH.............................................Page 7 Supplementary Table S5. Cox proportional hazards models of BNP in PAH with or without parenteral prostacyclin analogue................................................................... ....................................................................Page 8 Supplementary Table S6. Cox proportional hazards models including the number of PH-specific drugs in PAH adjusted for the independent prognostic factors.................................................................... ...........................Page 9 Supplementary Table S7. Baseline patient characteristics of PH- LHD......................................................Page 10 Supplementary Table S8. Cox proportional hazards models of baseline variables in PH-LHD.................Page 11 Supplementary Table S9. Cox proportional hazards models of baseline
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Kozu et al., Page 1
Online data supplement.
Current status of long-term prognosis among all subtypes of pulmonary hypertension in Japan
Supplementary Table S6. Cox proportional hazards models including the number of PH-specific drugs in PAH
adjusted for the independent prognostic factors...............................................................................................Page 9
Supplementary Table S7. Baseline patient characteristics of PH-LHD......................................................Page 10
Supplementary Table S8. Cox proportional hazards models of baseline variables in PH-LHD.................Page 11
Supplementary Table S9. Cox proportional hazards models of baseline variables in CTEPH...................Page 12
Supplementary Table S10. Cox proportional hazards models of BPA in CTEPH......................................Page 13
Supplementary Table S11. Comparison of the prognosis of patients with PAH between the Japanese registry and
other recent registries...............................................................................................................................Page 14
Supplementary Table S12. Comparison of the prognosis of patients with CTEPH between the Japanese registry
and other recent registries...............................................................................................................................Page 17
Supplementary Fig. S1. Study flow chart....................................................................................................Page 19
Supplementary Fig. S2. Long-term prognosis of patients with pulmonary hypertension in terms of incident vs.
saturation; WHO FC, World Health Organization functional class; 6MWD, 6-minute walk distance. *Percentage of the cases in which the data were obtained. †P<0.01 in comparison to IPAH/HPAH; ‡P<0.01 in
comparison to non-SSc CTD; §P<0.01 in comparison to Portal HT; ‖P<0.01 in comparison to CHD.
Kozu et al., Page 4
Supplementary Table S2. Baseline patient characteristics of PAH by maximum medication reached
during follow-up
Monotherapy Double combination therapy
Triple combination therapy
N 55 101 131Follow-up duration, years 5.0±3.8 4.9±3.3 5.6±4.3
PAH subgroup
IPAH/HPAH 14 (25) 26 (26) 55 (42)
Drug- and toxin-induced 1 (2) 0 0
CTD 24 (44) 54 (53) 43 (33)
Portal HT 6 (11) 11 (11) 8 (6)
CHD 10 (18) 10 (10) 24 (18)
CTD + CHD 0 0 1 (1)
Male 14 (25) 19 (19) 32 (24)
Age, years 55±18‡ 51±17‡ 45±20
BMI, kg/m2 21±4 21±4 21±4
WHO FC I* 5 (9) 8 (8) 9 (7)
II 20 (38) 31 (33) 53 (41)
III 24 (45) 45 (47) 59 (45)
IV 4 (8) 11 (12) 9 (7)
6MWD, m 305±146 350±144 357±119
BNP, pg/ml 169 (38-368) 93 (32-236) 97 (35-308)
eGFR, ml/min/1.73m2 80±38 75±26 81±54
FVC, % predicted 79±23 84±20 85±20
FEV1, % predicted 83±24 88±20§ 81±20
DLCO, % predicted 59±26 54±25 60±23
mPAP, mmHg 41±17‡ 43±14‡ 51±18
PAWP, mmHg 9±5 9±5 9±5
RAP, mmHg 6±4 6±4 6±4
CI, L/min/m2 3.1±1.0 2.9±0.9 2.8±1.2
PVR, Wood units 6.3 (4.0-10.4)‡ 7.5 (4.8-11.4)‡ 10.4 (6.0-14.0)
soluble guanylate cyclase; SvO2, mixed venous oxygen saturation; WHO FC, World Health Organization
functional class; 6MWD, 6-minute walk distance. *Percentage of the cases in which the data were obtained. †P<0.01 in comparison to double combination therapy; ‡P<0.01 in comparison to triple combination therapy; §P<0.05 in comparison to triple combination therapy.
Kozu et al., Page 6
Supplementary Table S3. Cox proportional hazards models of baseline variables in PAH
Univariable Multivariable
HR (95% CI) P value HR (95% CI) P value
Male 1.75 (1.10-2.72) 0.02 2.33 (1.35-3.94) 0.003
Age <30, years 1.49 (0.77-2.83) 0.23 1.15 (0.51-2.54) 0.72
30≤ Age <45, years Reference Reference
45≤ Age <60, years 1.29 (0.68-2.42) 0.44 1.45 (0.67-3.14) 0.34
60≤ Age <75, years 1.60 (0.86-2.99) 0.14 1.53 (0.69-3.40) 0.29
Age ≥75, years 3.47 (1.63-7.08) 0.002 4.99 (2.11-11.6) 0.0004
pulmonary vascular resistance; RAP, right atrial pressure; REHAP, Spanish Registry of Pulmonary Arterial
Hypertension; REVEAL, Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension
Disease Management; SvO2, mixed venous oxygen saturation; WHO FC, World Health Organization
functional class.*Including one patient with CHD. †Data expressed as median. ‡Initial therapy.§At enrollment. This data was obtained from REVEAL registry reported by Benza et al. in 2010 [10].
Kozu et al., Page 17
Supplementary Table S12. Comparison of the prognosis of patients with CTEPH between the Japanese registry and other recent registries
Japanese Swiss[5] Giessen[6] ASPIRE[4] REHAP[15]International
registry[16]
Intervention PEA Non-PEA Overall Non-PEA PEA Non-PEA Overall PEA PEA Non-PEA PEA Non-PEA
1 year 92.9 97.4 NA 91 96.1 84.5 89 NA 97 93 93 88
3 years 88.8 94.7 NA 77 87.1 72.5 71 83 91 81 89 70
5 years 88.8 92.4 NA NA 76.7 61.8 NA NA 86 65 NA NA
Data are presented as mean, unless otherwise stated. ASPIRE, Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Center; CHD, congenital
Spanish Registry of Pulmonary Arterial Hypertension; SvO2, mixed venous oxygen saturation; Tx, therapy; WHO FC, World Health Organization functional class.*Data expressed as median. †Data from all of CTEPH patients. ‡Initial therapy. §Oral monotherapy.