Figures
- FIGURE 1
Effects of riociguat on the right ventricle in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. White dotted line indicates the position of the right ventricular (RV) wall in a healthy heart. RA: right atrium; PA: pulmonary artery; PVR: pulmonary vascular resistance; mPAP: mean pulmonary arterial pressure; CI: cardiac index; SVI: stroke volume index.
- FIGURE 2
Patients with pulmonary hypertension receiving riociguat show a significant reduction in right atrial (RA) and right ventricular (RV) areas compared with baseline at all time points. Figure modified from Marra et al. [36] and redistributed under the Creative Commons Attribution 4.0 International license: https://creativecommons.org/licenses/by/4.0/legalcode. #: compared to baseline.
Tables
- TABLE 1
Overview of the effects of riociguat on the right ventricle in clinical studies
Study design Riociguat treatment Changes to the right ventricle following riociguat treatment compared with baseline# Reference Retrospective single-centre study of 39 patients with PH (21 PAH, 18 CTEPH) in PATENT-1, PATENT-2, PATENT PLUS, CHEST-1, CHEST-2 or CTEPH Early Access Study (EAS) 1.0–2.5 mg three times daily for 3–12 months Function Increased TAPSE at 6 months (p=0.025) and 12 months (p=0.002)
Increased tricuspid annular velocity at 12 months (p=0.006)
Decreased systolic PA pressure and mPAP at 3 months (both p=0.03)
Increased CO and CI at 3 months (both p<0.001)
Decreased PVR at 3 months (p<0.001)
Decreased RV area at 3 months (p=0.002), 6 months and 12 months (both p<0.001)
Decreased RA area at 6 months (p=0.06) and 12 months (p<0.001)
Decreased RV free wall thickness at 3 months (p<0.05), 6 months and 12 months (both p<0.01)
Improved RV remodelling at 6 months (p=0.003) and 12 months (p=0.03)
[35] Retrospective multicentre study of 71 patients with PH (32 PAH, 39 CTEPH) in phase II, PATENT-1, PATENT-2, PATENT PLUS, CHEST-1, CHEST-2 or CTEPH EAS (RIVER study) 1.0–2.5 mg three times daily for 3–12 months Function Improved RV systolic function at 12 months (p=0.016)
Increased TAPSE at 12 months (p<0.001)
Decreased tricuspid regurgitation velocity at 12 months (p=0.005)
RV fractional area change at 12 months (p<0.001)
Decreased RV area at 3 months, 6 months and 12 months (all p<0.001)
Decreased RA area at 6 months and 12 months (both p<0.001)
Decreased RV thickness at 12 months (p=0.023)
Decreased PA diameter at 12 months (p=0.014)
[36] Retrospective study of 27 patients with PH (7 PAH, 20 CTEPH) Mean dose of 7.3±0.7 mg administered for a mean 220 days Function Increased RV fractional area change (p=0.005)
Decreased RV global longitudinal strain (p=0.0006)
Decreased basal, mid and longitudinal RV diameters (all p=0.001)
Decreased RV end-diastolic area index (p=0.0005)
[37] Retrospective analysis of 45 patients with PH (14 PAH, 31 CTEPH) Mean final daily dose of 7.2±0.9 mg administered for a mean 234 days Function Decreased mPAP (p=0.008)
Increased CI (p=0.04)
Decreased PVR (p=0.016)
Increased RV systolic excursion velocity (p=0.001)
Decreased RV global longitudinal strain (p<0.001)
Increased fractional area change (p<0.001)
Decreased RV dyssynchrony index (p=0.012)
Decreased estimated PA systolic pressure (p<0.001)
Decreased tricuspid regurgitation pressure gradient (p<0.001)
Decreased RV basal (p<0.001), mid (p<0.001) and longitudinal (p=0.002) diameters
Decreased RV end-diastolic and end-systolic area indices (p<0.001)
Decreased RA area index (p=0.0014)
[38] Post hoc analysis of 341 patients with PAH in PATENT-1 and 238 patients with CTEPH in CHEST-1 Up to 2.5 mg three times daily for 12 weeks for PATENT-1 and 16 weeks for CHEST-1 Function compared with placebo treated Increased stroke volume, SVI and cardiac efficiency in PATENT-1 and CHEST-1 (all p<0.0001)
Increased RV work in PATENT-1 (p=0.0002) and CHEST-1 (p=0.0317)
Increased RV work index in PATENT-1 (p<0.0001) and CHEST-1 (p=0.0338)
Increased RV power in PATENT-1 (p=0.0002) and CHEST-1 (p=0.0317)
Decreased PA elastance in PATENT-1 and CHEST-1 (both p<0.0001)
[39] Single-centre prospective randomised open-label trial of 21 patients with CTEPH who had mPAP <30 mmHg after undergoing BPA Up to 2.5 mg three times daily for 6 months (8 of the 10 patients in the riociguat arm received less than the maximum dose) Function at peak workload compared with standard of care treated Increased CO and decreased PVR at 6 months (both p<0.01)
Trend of improved mPAP–CO slope at 6 months (p=0.09)
[40] Post hoc analysis of the RESPITE study in 61 patients with PAH 1.0–2.5 mg three times daily for 24 weeks following a 1–3-day PDE5i treatment-free period Function following switch Increased cardiac efficiency (p=0.0004)
Increased stroke volume (p=0.0044)
Increased SVI (p=0.0052)
Maintained RV work (p=0.1770)
Maintained RV work index (p=0.0793)
Maintained RV power (p=0.1770)
Maintained PA elastance (p=0.0888)
[41] Retrospective analysis of 28 patients with CTEPH who were switched from sildenafil to riociguat Up to 2.5 mg three times daily for a median follow-up time of 5.8 (3.6–7.9) months following switching Function following switch Decreased PVR (p=0.005)
Decreased systemic vascular resistance (p=0.001)
Decreased mPAP (p=0.03)
Increased CO (p=0.002)
[42] Single-centre retrospective analysis of 26 patients with PAH receiving triple therapy with riociguat, macitentan and selexipag Of 26 patients, 24 received riociguat up-titrated to maximum tolerated dose for a median observation period of 441 days Function Decreased mean RA pressure (p=0.005)
Decreased mPAP (p<0.001)
Increased CO (p<0.001)
Increased CI (p<0.001)
Decreased PVR (p<0.001)
Increased TAPSE (p=0.001)
Increased RV systolic excursion velocity (p=0.001)
Increased fractional area change (p<0.001)
Decreased RV end-systolic area (p=0.006)
[43] Prospective study of 6 patients with CTEPH 0.5–2.5 mg three times daily for 6 months Function Increased RV SVI (p=0.03)
Trend of increased RV ejection fraction (p=0.09)
Trend of decreased myocardial fibrosis volume and mass (both p=0.09)
[44] Single-site pilot study of 20 patients with PAH (12 treatment-naïve patients and 8 who were switched from sildenafil to riociguat) 1.0–2.5 mg three times daily for 12 weeks Function Decreased systolic PA pressure (p=0.003)
Decreased mPAP (p=0.007)
Increased RV fractional area change (p=0.04)
Decreased RV end-diastolic volume (p=0.003)
Decreased RV end-systolic volume (p=0.002)
Decreased RV basal diameter in treatment-naïve patients only (p=0.03); not significant in switched patients
Decreased RV–PA coupling (p=0.02)
[45] RV: right ventricular; PH: pulmonary hypertension; PAH: pulmonary arterial hypertension; CTEPH: chronic thromboembolic pulmonary hypertension; TAPSE: tricuspid annular plane systolic excursion; PA: pulmonary artery; mPAP: mean pulmonary arterial pressure; CO: cardiac output; CI: cardiac index; PVR: pulmonary vascular resistance; RA: right atrial; BPA: balloon pulmonary angioplasty; PDE5i: phosphodiesterase-5 inhibitors; SVI: stroke volume index. #: outcomes compared with baseline unless otherwise stated.
Supplementary Material
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Supplementary material err-0061-2022.supplement
Jump To
- Article
- Abstract
- Abstract
- Introduction
- Effect of riociguat on the right ventricle in preclinical models
- Effect of riociguat on RV function in clinical studies
- Effect of riociguat on RV hypertrophy in clinical studies
- Effect of riociguat on other aspects of RV remodelling in clinical studies
- Conclusions
- Supplementary material
- Acknowledgements
- Footnotes
- References
- Figures & Data
- Info & Metrics