Table 1.
Clinical characteristics of two patients with biallelic EIF2AK4 mutation-associated PAH
| Patient 1 (40 female) | Patient 2 (34 female) | |
|---|---|---|
| Genetic mutation | Homozygous pathogenic missense variant EIF2AK4: c,1849G>C, p.(Ala617Pro) | Homozygous pathogenic EIF2AK4, variant details unavailable |
| Follow-up duration | 1 year and 6 months | 8 years and 3 months |
| Digital clubbing | Absent | Absent |
| Echocardiogram at diagnosis | ||
| RV systolic function | Moderately reduced | Mildly reduced |
| FAC (%) | 25 | 27 |
| RV morphology | Moderate-severely dilated | Mildly dilated |
| TR Vmax (m/s) | 3.50 | Unable to quantify |
| PASP (mmHg) | 56 mmHg | Unable to quantify |
| ESC probability of PAH | High | Intermediate |
| Cardiac MRI at diagnosis | ||
| LVEF (%) | 64 | 61 |
| RVEF (%) | 58 | 51 |
| RV EDV (mL) | 176 | 108 |
| RV ESV (mL) | 75 | 53 |
| RV SV (mL) | 101 | 55 |
| Gadolinium enhancement | Late enhancement in RV septal insertion | No significant early/late |
| Haemodynamics at diagnosis | ||
| PAP (S/D/M) (mmHg) | 60/21/39 | 61/27/41 |
| PCWP (mmHg) | 2 | 6 |
| CO (L/min) | 4.15 | 4.67 |
| PVR (WU) | 8.9 | 7.5 |
| Nitric oxide vasoreactivity testing | No response | No response |
| Haemodynamics at 12-month follow-up | ||
| PAP (mmHg) | 52/24/34 | 32/16/24 |
| PCWP (mmHg) | 8 | 12 |
| CO (L/min) | 9.4 | 5.6 |
| PVR (WU) | 2.8 | 2.1 |
| Pulmonary vasodilator treatment | Tadalafil, ambrisentan | Sildenafil, ambrisentan |
| Contrast echocardiogram findings | 4 months after presentation; moderate right-to-left shunt, late contrast in LA | 3 years after presentation; moderate right-to-left shunt from left pulmonary veins |
| CT findings | Centrilobular ground glass opacification | Subtle interlobular septal thickening and small calcified lung nodules |
| Lung function (at diagnosis) | ||
| FEV1 (%) | 108 | 93 |
| FVC (%) | 117 | 100 |
| DLco (%) | 37 | 24 |
| Kco (%) | 40 | 30 |
| Cardiopulmonary exercise testing data (on pulmonary vasodilator treatment) | ||
| Peak VO2 (%) | 53 | 34 |
| VE/VCO2 slope | 55 | 56 |
| Peak O2 sats (%) | 90 | 94 |
| Rest A—a gradient (kPa) | 5.3 | – |
| Peak A—a gradient (kPa) | 9.8 | – |
| Rest Vd/Vt (%) | 19 | – |
| Peak Vd/Vt (%) | 32 | – |
| Lactate (mmol/L) | 2.9 | 3.1 |
PAP, pulmonary artery pressure; S/D/M, systolic/diastolic/mean; PCWP, pulmonary capillary wedge pressure; CO, cardiac output; PVR, pulmonary vascular resistance; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; TLco, diffusion capacity for carbon monoxide; Kco, diffusion capacity for carbon monoxide/alveolar ventilation.