Figures
- FIGURE 1
Treatment algorithm for managing chronic thromboembolic pulmonary hypertension (CTEPH), from the European Society of Cardiology/European Respiratory Society guidelines [1, 2]. Pulmonary endarterectomy is the standard of care for patients with technically operable CTEPH and an acceptable risk/benefit ratio for surgery. #: technically operable patients with a non-acceptable risk/benefit ratio can be considered for balloon pulmonary angioplasty (BPA). ¶: in some centres, medical therapy and BPA are initiated concurrently. PH: pulmonary hypertension. Reproduced and modified from [1, 2] with permission.
- FIGURE 2
The management options for chronic thromboembolic pulmonary hypertension (CTEPH) target different pathogenic manifestations in different parts of the pulmonary vascular bed. A schematic representation of a pulmonary artery is shown (note that vessel diameter is not to scale). Pulmonary endarterectomy (PEA) is used to remove thromboembolic lesions primarily in the proximal main artery (diameter of ∼3 cm), and lobar and segmental arteries [13, 14]; in expert surgical centres, lesions in distally located mid-segmental and sub-segmental branches can be targeted by PEA [14], down to vessels of 2 mm in diameter. Balloon pulmonary angioplasty (BPA) mainly targets distal lesions in the segmental and sub-segmental vasculature, down to small pulmonary arteries of 2–5 mm in diameter. Medical therapy targets microvasculopathy, including intimal thickening and fibromuscular proliferation, in vessels of 0.1–0.5 mm in diameter [10]. a) Computed tomography scan of a pulmonary artery. b) Organised fibrotic material removed during PEA. c) Selective pulmonary angiogram of segmental and sub-segmental pulmonary arteries, showing irregular vessel contour and occlusion, typical of CTEPH. d) Microscopic examination showing a luminal filling defect with recanalised chronic thrombus (web lesion) and no evidence of vasculopathy in the sub-segmental artery. e) Intimal fibromuscular proliferation. Reproduced from [20] with permission. f) Plexiform lesion and vessel occlusion due to vasculopathy and proliferation.
Tables
- TABLE 1
Randomised controlled trial data on the use of medical therapies in patients with chronic thromboembolic pulmonary hypertension
CHEST-1 [68] Suntharalingam et al. [69] MERIT-1 [70] BENEFiT [71] Patients n 261 19 80 157 Active treatment Riociguat Sildenafil Macitentan Bosentan Control Placebo Placebo Placebo Placebo Treatment duration weeks 16 12 24 16 Population n (%) Inoperable 189 (72.4) 10 (52.6) 80 (100) 96 (70.1) Persistent/recurrent PH post-pulmonary endarterectomy 72 (27.6) 9 (47.4) 0 41 (29.9) Use of PAH therapy at baseline n (%) No 261 (100.0) 19 (100.0) 31 (38.8) 157 (100.0) Yes 0 0 49 (61.3) 0 Primary end-point Change in 6MWD from baseline to week 16 Change in 6MWD from baseline to week 12 PVR at week 16 as a percentage of baseline Change in PVR and 6MWD from baseline to week 16 (co-primary end-points) Treatment effect on 6MWD +46 (25–67) m, p<0.001# +18 (−24–59) m, p=ns +34 (3–65) m, p<0.05# +2 (−23–27) m, p=ns Treatment effect on PVR −246 (−303– −190) dyn·s·cm−5, p<0.001# −197 (−389– −6) dyn·s·cm−5, p<0.05 0.84¶ (0.70–0.99), p<0.05+ −24%§ (−32– −16%), p<0.0001+ Treatment effect on mPAP −5 (−7–−3) mmHg, p<0.001# −6 (−12–0) mmHg, p=ns −2 (−6–2) mmHg, p=ns# −3 (−5–0) mmHg, p=ns Data are presented as n, n (%) or mean difference (95% CI), with p-value, between active and control groups, unless otherwise stated. PH: pulmonary hypertension; PAH: pulmonary arterial hypertension; 6MWD: 6-min walk distance; PVR: pulmonary vascular resistance; mPAP: mean pulmonary arterial pressure; ns: nonsignificant. #: treatment effect is the least-squares mean difference; ¶: corresponds to a 16% reduction, PVR decreased by 206 dyn·s·cm−5 in the macitentan group and 86 dyn·s·cm−5 in the placebo group; +: treatment effect is the ratio of geometric means; §: PVR decreased by 146 dyn·s·cm−5 in the bosentan group and increased by 30 dyn·s·cm−5 in the placebo group.
Supplementary Material
M. Madani ERR-0105-2017_Madani
T. Ogo ERR-0105-2017_Ogo
G. Simonneau ERR-0105-2017_Simonneau
