Table 4.
Vasodilator response* and PAH medication among TET2 deleterious variant carrier
| Vasodilator used | Cohort APAH+IPAH excluding TET2 carriers | APAH+IPAH germline TET2 carriers | APAH+IPAH somatic TET2 carriers | APAH+IPAH TET2 carriers† |
|---|---|---|---|---|
| Oxygen + Nitric Oxide | 50/286 (17.5%) | 0/3 (0%) | 0/1 (0%)‡ | 0/3 (0%) |
| IV Epoprostenol | 13/110 (11.8%) | - | - | - |
| Inhaled Nitric Oxide | 60/564 (10.6%) | 0/2 (0%) | 0/1 (0%) | 0/3 (0%) |
| Oxygen | 5/16 (31.2%) | - | - | - |
| IV Nitroprusside | 1/7 (14.3%) | - | - | - |
| IV Adenosine | 5/37 (13.5%) | - | 0/1 (0%) | 0/1 (0%) |
| Inhaled Iloprost | 1/2 (50%) | - | - | - |
| Inhaled Epoprostenol | 1/6 (16.7%) | - | - | - |
| Alprostadil | 2/8 (25%) | - | - | - |
| Calcium Channel Blocker | 0/3 (0%) | - | - | - |
| Unknown | 2/16 (12.5%) | - | - | - |
| Total | 140/1055 (13.2%) | 0/5 (0%) | 0/3 (0%) | 0/7 (0%) |
| PAH medication | Cohort APAH+IPAH excluding TET2 carriers | APAH+IPAH TET2 carriers† | ||
| PDE5 inhibitor | 2014/2674 (75.3%) | 14/18 (77.8%) | ||
| Prostacyclin analog | 1356/2674 (50.7%) | 10/18 (55.6%) | ||
| Endothelin receptor inhibitor | 1036/2674 (38.7%) | 11/18 (61.1%)‡ | ||
| Stimulator of soluble guanylate cyclase | 44/2674 (1.6%) | 1/18 (5.6%) | ||
| Calcium channel blocker | 239/2674 (8.9 %) | 0/18 (0%) | ||
| RTK inhibitor | 5/2674 (0.2%) | 0/18 (0%) | ||
| Unknown | 29/2674 (1.1%) | 1/18 (5.6%) |
*
Positive vasodilator responders were defined according to standard criteria as a drop of mean pulmonary arterial pressure (mPAP) >10mmHg to mPAP at rest <40mmHg with preserved or improved cardiac output.
†
Somatic + germline carrier (patient 29–016)
‡
Difference statistically significant compared to cohort APAH+IPAH excluding DNMT3A and TET2 carriers; p< 0.05, z-test.
APAH, associated PAH; IPAH, idiopathic PAH; IV, intra-venous; PDE5, phosphodiesterase 5; RTK, receptor tyrosine kinase