Table 1.
Demographic and Clinical Characteristics at Diagnosis of the Patient Population Included in the Genotype–Phenotype Dataset
| BMPR2 (n = 162) | No Causal Variant Identified (n = 741) | TBX4 (n = 98) | P Value | Available (Total n) | |
|---|---|---|---|---|---|
| Primary diagnosis | 1,001 | ||||
| 1.1 Idiopathic PAH, including drug and toxin induced | 107 (66.0) | 741 (100) | 58 (59.2) | ||
| 1.2 Heritable PAH | 53 (32.7) | — | 17 (17.3) | ||
| 1.4.1 PAH associated with connective tissue disease | 1 (0.62) | — | 2 (2.04) | ||
| 1.4.4 PAH associated with congenital heart disease | 1 (0.62) | — | 11 (11.2) | ||
| 1.6 PAH with overt features of venous/capillary (PVOD/PCH) involvement | — | — | 1 (1.02) | ||
| 3.5 Developmental lung disorders | — | — | 9 (9.18) | ||
| Sex: female | 107 (66.0) | 530 (71.5) | 62 (63.9) | 0.156 | 1,000 |
| Smoking history: past/current, adults only | 53 (39.3) | 293 (53.3) | 10 (47.6) | 0.039 | 706 |
| Exposure to drug or toxins: yes | 6 (3.70) | 45 (6.07) | 7 (19.4) | 0.007 | 939 |
| Ethnicity | 966 | ||||
| European | 137 (84.6) | 630 (85.0) | 53 (84.1) | ||
| Finnish European | — | 1 (0.13) | — | ||
| African | 2 (1.23) | 20 (2.70) | 5 (7.94) | ||
| East Asian | 2 (1.23) | 6 (0.81) | 1 (1.59) | ||
| South Asian | 6 (3.70) | 48 (6.48) | 1 (1.59) | ||
| Other | 15 (9.26) | 36 (4.86) | 3 (4.76) | ||
| Age at diagnosis of lung disease, yr | 39 (31–51) | 51 (38–66) | 14 (2–48) | <0.001 | 997 |
| Age at transplantation or death, yr | 52 (43–61) | 67 (53–75) | 64 (1–71) | <0.001 | 302 |
| WHO functional class | 0.277 | 918 | |||
| I | 2 (1.24) | 15 (2.11) | 2 (4.44) | ||
| II | 32 (19.9) | 144 (20.2) | 10 (22.2) | ||
| III | 96 (59.6) | 466 (65.4) | 27 (60.0) | ||
| IV | 31 (19.3) | 87 (12.2) | 6 (13.3) | ||
| Exercise test | |||||
| Distance, m | 350 (276–420) | 330 (210–410) | 371 (308–422) | 0.028 | 810 |
| Pretest saturation | 96.0 (94.0–98.0) | 96.0 (93.0–97.0) | 97.5 (95.5–98.0) | 0.006 | 738 |
| Post-test saturation | 94.0 (89.0–96.8) | 91.0 (85.0–95.0) | 95.5 (86.5–97.0) | 0.001 | 683 |
| Lung function, % predicted | |||||
| FEV1 | 91.0 (79.0–100) | 85.0 (72.3–96.0) | 82.0 (70.0–98.0) | 0.001 | 719 |
| FVC | 99.7 (17.2) | 93.2 (19.4) | 88.0 (17.7) | <0.001 | 703 |
| Kco | 83.4 (74.2–96.5) | 68.0 (49.0–83.0) | 72.0 (59.8–89.8) | <0.001 | 516 |
| TLC | 96.0 (89.0–106) | 94.0 (85.0–104) | 104 (98.0–110) | 0.044 | 511 |
| Hemodynamics | |||||
| mPAP, mm Hg | 57.0 (52.0–66.8) | 52.0 (42.0–61.0) | 60.5 (48.2–82.2) | <0.001 | 916 |
| mPAWP, mm Hg | 10.0 (7.00–12.0) | 9.00 (7.00–12.0) | 9.00 (7.00–11.0) | 0.841 | 822 |
| PVR, WU | 14.5 (10.8–20.4) | 10.3 (7.06–13.9) | 12.8 (8.25–16.2) | <0.001 | 767 |
| CO, L/min | 3.30 (2.69–3.94) | 4.04 (3.25–5.10) | 3.65 (3.09–4.61) | <0.001 | 852 |
| CI, L/min/m2 | 1.90 (1.51–2.23) | 2.30 (1.80–2.80) | 2.63 (1.98–3.20) | <0.001 | 503 |
| Vasoresponders | 1 (1.28) | 51 (17.7) | 6 (10.2) | 0.001 | 425 |
| Increased BNP (>50 pg/ml) or NT-proBNP (>300 pg/ml) | 34 (97.1) | 140 (79.1) | 5 (71.4) | 0.011 | 219 |
Definition of abbreviations: BMPR2 = Bone Morphogenetic Protein Receptor type 2; BNP = brain natriuretic peptide; CI = cardiac index; CO = cardiac output; mPAP = mean pulmonary artery pressure; mPAWP = mean pulmonary artery wedge pressure; NT-pro-BNP = N-terminal pro-brain natriuretic peptide; PCH = pulmonary capillary hemangiomatosis; PVOD = pulmonary venoocclusive disease; PVR = pulmonary vascular resistance; TBX4 = T-BOX transcription factor 4; WHO = World Health Organization; WU = Wood units = mm Hg/L/min.
Data are presented as n (%) or median (interquartile range). Heterozygous carriers of TBX4 variants shown to be benign by our functional studies were excluded.