case_images: PMC9751701_01
case_images: Results of acute vasoreactivity testing and timeline of dose titration of riociguat and inhaled nitric oxide therapies for patiennt 1. (A) Results of hemodynamic evaluation for patient 1. With acute increase in nitric oxide dose delivery, we observed (A) decreased pulmonary vascular resistance and (B) increased pulmonary blood flow despite background therapy with sildenafil, treprostinil, high fractional inspired oxygen, and nitric oxide at 20 ppm. (B) Timeline for initiation of riociguat therapy and weaning off inhaled nitric oxide. Riociguat therapy was started at very low dose (0.006 mg/kg/dose = 0.05 mg total dose once per day) and uptitrated slowly over 7 weeks to a dose of 2 mg/dose TID while nitric oxide was weaned over a similar timeframe. Not shown, over the subsequent 6 months his dose was titrated up to final dose of 2.5 mg TID. O2, oxygen; NO, inhaled nitric oxide; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance; Qp, pulmonary flow; Qs, systemic flow.
case_images: fped-10-1014922-g001.jpg
case_images: PMC9751701_01_fped-10-1014922-g001.jpg
case_images: F1
case_images: His Qp:Qs improved with increasing doses of iNO and treprostinil (Figure 1A). Riociguat was gradually increased to 2 mg/dose TID with iNO weaned and eventually discontinued 7 weeks after riociguat initiation (Figure 1B).
case_images: PMC9751701_02
case_images: Results of acute vasoreactivity testing and timeline of dose titration of riociguat and inhaled nitric oxide therapies for patient 2. (A) Results of acute vasoreactivity testing for patient 2. Acute challenge with increased oxygen (FiO2 1.0) and addition of inhaled nitric oxide at 40 ppm resulted in significant improvement of (A) mean pulmonary artery pressure, (B) indexed pulmonary vascular resistance, (C) PVR:SVR ratio and (D) Qp:Qs ratio. (B) Timeline for initiation of riociguat therapy and weaning off inhaled nitric oxide. Patient 2 was started on riociguat 0.01 mg/kg/dose (0.05 mg total dose three times per day) with a daily dose increase, achieving 0.5 mg/dose TID after 1 week. Nitric oxide was weaned over that same week to off without adverse clinical sequelae noted. Not shown, his dose was titrated up to 2 mg TID over the subsequent four months. O2, oxygen; NO, inhaled nitric oxide; PVRi, indexed pulmonary vascular resistance; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance; Qp, pulmonary flow; Qs, systemic flow.
case_images: fped-10-1014922-g002.jpg
case_images: PMC9751701_02_fped-10-1014922-g002.jpg
case_images: F2
case_images: Cardiac catheterization at 7 weeks of age showed mPAP 88 mmHg (sMAP 56 mmHg) and PVRi 28.2 WU*m2 (oxygen), which decreased to mPAP 62 mmHg (sMAP 59 mmHg), and PVRi 12 WU*m2 (iNO + oxygen) (Figure 2A). He tolerated a slow wean off iNO and noninvasive ventilation to oxygen supplementation via nasal cannula without clinical complications and with improved PAH by echocardiogram over the course of 1 week (Figure 2B).