The changing landscape of chronic thromboembolic pulmonary hypertension management

Abstract

For patients with chronic thromboembolic pulmonary hypertension (CTEPH), the current standard of care involves surgical removal of fibro-thrombotic obstructions by pulmonary endarterectomy. While this approach has excellent outcomes, significant proportions of patients are not eligible for surgery or suffer from persistent/recurrent pulmonary hypertension after the procedure. The availability of balloon pulmonary angioplasty and the approval of the first medical therapy for use in CTEPH have significantly improved the outlook for patients ineligible for pulmonary endarterectomy. In this comprehensive review, we discuss the latest developments in the rapidly evolving field of CTEPH. These include improvements in imaging modalities and advances in surgical and interventional techniques, which have broadened the range of patients who may benefit from such procedures. The efficacy and safety of targeted medical therapies in CTEPH patients are also discussed, particularly the encouraging data from the recent MERIT-1 trial, which demonstrated the beneficial impact of using macitentan to treat patients with inoperable CTEPH, including those on background therapy. As the treatment options for CTEPH improve, hybrid management involving more than one intervention in the same patient may become a viable option in the near future.

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.