TABLE 1.
Characteristics of BMPR2 mutation carriers without pulmonary arterial hypertension (PAH) and patients diagnosed with PAH in DELPHI-2 and long-term follow-up
| DELPHI-2 (n=55) | Long-term follow-up (n=36) | |||||
| No PAH at inclusion (n=53) | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | |
| Demographic data | ||||||
| Age years | 37.1 (18–67.5); (24.9–49.7) | 25.5 | 78.1 | 49.9 | 72.5 | 46.8 |
| Male/female | 26/27 | Female | Female | Female | Female | Male |
| Tobacco exposure >5 pack-years | 18 (34) | Yes | No | No | No | Yes |
| BMI kg·m−2 | 22.5 (16.8–32.2); (21.7–26.1) | 22.0 | 25.2 | 22.9 | 21.3 | 24.9 |
| Systemic hypertension | 10 (19) | No | Yes | No | No | No |
| Diabetes | 3 (6) | No | Yes | No | No | No |
| Dyslipidaemia | 3 (6) | No | No | No | No | No |
| Delay between symptoms and diagnosis months | NA | NA | NA | 3 | NA | 3–6 |
| Potential additional risk factor | NA | Pregnancy | None | Chemotherapy | Chemotherapy | None |
| Functional parameters | ||||||
| NYHA FC I–IV | I | I | I | II | I | II |
| 6MWD m | 539 (368–693); (486–599) | 533 | 420 | 397 | 412 | 505 |
| FEV1 % pred | 105 (69–141); (97–113) | 86 | 152 | 91 | 119 | 91 |
| FVC % pred | 108 (75–140); (98–117) | 89 | 162 | 103 | 144 | 96 |
| DLCO % pred | 76 (39–126); (69–87) | 50 | 63 | 42 | 52 | 82 |
| DLCO/VA % pred | 89 (49–126); (74–100) | 62 | 66 | 65 | 58 | 104 |
| CPET | ||||||
| V′O2 at peak % pred | 81 (47–132); (65.5–91.5) | 70 | 89 | 58 | 81 | 62 |
| V′E at peak % pred | 76.2 (37.8–156.8); (56.7–101.8) | 74 | 53.9 | 63.3 | 63.5 | 72.4 |
| VD/VT | 0.21 (0.06–0.39); (0.12–0.24) | 0.15 | 0.27 | 0.53 | 0.49 | NA |
| V′E/V′CO2 at anaerobic threshold | 33 (24–66); (23.5–45) | 36 | 54 | 59 | 43 | 39 |
| V′O2/HR % pred | 88 (50–125); (77.5–101) | 100 | 98 | 60 | 122 | 78 |
| PaO2 at rest mmHg | 93 (75–118); (85–100) | 99 | 70 | 70 | 94 | 63 |
| PaO2 at peak mmHg | 106 (85–124); (97.5–114) | NA | 97 | 49 | 83 | NA |
| P(A–a)O2 mmHg | 12.7 (−5.6–32.8); (7.7–19.8) | 15.7 | 26 | 77 | 40 | NA |
| CPET probability score | 2 (0–6) | 4 | 9 | 10 | 8 | NA |
| Echocardiography | ||||||
| TRV m·s−1 | 2 (1.5–2.75)#; (1.85–2.3) | 2 | 2.65 | 4.2 | 3.3 | 4.4 |
| RA surface area cm2 | 13.0 (7.7–27.0); (10–15) | 15 | 14 | 19 | 16 | 21 |
| LA surface area cm2 | 14 (9.5–23); (12.5–17) | 15 | 9 | 12 | 17 | 13 |
| Diastolic RV surface area cm2 | 17.5 (8.0–28.0); (14–20) | 15.6 | 16 | 22.9 | 15.8 | 25 |
| Systolic RV surface area cm2 | 9.5 (3.7–15.0); (7–11) | 11 | 8 | 14.8 | 8.2 | 12 |
| RVEF % | 45 (30–71); (40–50) | 30 | 50 | 35 | 48 | 50 |
| TAPSE mm | 23 (16–28); (21–25) | 25 | 16 | 23 | 19 | 21 |
| RV Tei index | 0.24 (0.06–0.77); (0.18–0.30) | NA | NA | 0.2 | NA | 0.47 |
| Haemodynamics | ||||||
| mPAP mmHg | 14 (8–23); (13–17) | 26 | 25 | 43 | 29 | 50 |
| PAWP mmHg | 8 (2–14); (6–10) | 8 | 7 | 7 | 5 | 8 |
| Cardiac output L·min−1 | 6.03 (3.77–10.33); (5.30–7.00) | 7.27 | 4.05 | 3.93 | 3.27 | 4.57 |
| Cardiac index L·min−1·m−2 | 3.50 (2.20–5.44); (3.11–4.10) | 4.38 | 2.8 | 2.31 | 1.94 | 2.36 |
| SVI mL·m−2 | 51.6 (33.7–79.2); (43.6–53.5) | 55.4 | 35.0 | 46.8 | 32.3 | 31.9 |
| TPR WU | 2.5 (1.2–4.8); (1.9–3.0) | 3.58 | 6.17 | 10.93 | 8.88 | 10.95 |
| PVR WU | 1.0 (0.2–3.7); (0.7–1.4) | 2.5 | 4.4 | 9.2 | 7.3 | 9.2 |
| Acute vasodilator test | Not performed | Negative | Negative | Negative | Negative | Negative |
| Biological tests | ||||||
| Uricaemia µmol·L−1 (normal <357) | 286 (170–528); (231–374) | 250 | 465 | 306 | 270 | 603 |
| BNP ng·L−1 (normal <80) | 11 (5–60); (8.8–15.5) | 9 | 19 | NA | NA | NA |
| NT-proBNP ng·L−1 (normal <300) | NA | NA | NA | 484 | 252 | 437 |
All values are expressed as median (minimum–maximum range); (interquartile range), n or n (%). BMI: body mass index; NYHA FC: New York Heart Association Functional Class; 6MWD: 6-min walk distance; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide; VA: alveolar volume; CPET: cardiopulmonary exercise testing; V′O2: oxygen consumption corrected for body weight; V′E: minute ventilation; VD/VT: physiological dead space fraction; V′CO2: carbon dioxide production; HR: heart rate; PaO2: arterial oxygen tension; P(A–a)O2: alveolar–arterial oxygen tension difference; TRV: tricuspid regurgitation velocity; RA; right atrium; LA: left atrium; RV: right ventricle; RVEF: right ventricular ejection fraction; TAPSE: tricuspid annular plane systolic excursion; mPAP: mean pulmonary arterial pressure; PAWP: pulmonary arterial wedge pressure; SVI: stroke volume index; TPR: total pulmonary resistance; PVR: pulmonary vascular resistance; BNP: brain natriuretic peptide; NT-proBNP: N-terminal pro-BNP; NA: not available. #: n=28.