Managing chronic thromboembolic pulmonary hypertension: pharmacological treatment options

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition in which organised thrombi obstruct the pulmonary vessels, causing increased pulmonary vascular resistance, progressive pulmonary hypertension (PH) and right heart failure. The treatment of choice is pulmonary endarterectomy, which restores pulmonary haemodynamics with acceptable periprocedural mortality rates in the majority of suitable patients. However, CTEPH may be inoperable owing to surgically inaccessible thrombi or comorbid diseases that confer an unacceptably high risk.Pharmacotherapies, although not yet approved, may be useful in this situation or for treating residual or recurrent PH following surgery. Vasodilator drugs for PH are attracting growing interest as potential treatments for CTEPH because this disease has recently been labelled as a ''dual'' pulmonary vascular disorder: major vessel obstruction and remodelling is combined with a small vessel arteriopathy that is histologically indistinguishable from the classical pulmonary arteriopathy observed in pulmonary arterial hypertension.Of three completed randomised controlled trials in patients with CTEPH, only one was powered to detect a treatment effect. The BENEFIT trial employed the dual endothelin-receptor antagonist bosentan. Although haemodynamics improved significantly, the second component of the primary end-point, exercise capacity, was not met.More evidence is required to resolve whether vasodilator treatments are beneficial for inoperable chronic thromboembolic pulmonary hypertension.

Contrast‐enhanced multidetector‐row computed tomography vs. Time‐resolved magnetic resonance angiography vs. contrast‐enhanced perfusion MRI: Assessment of treatment response by patients with inoperable chronic thromboembolic pulmonary hypertension

“…CTEPH is related to an increase in the resistance to flow through the pulmonary arteries, which results initially from obstruction of pulmonary arterial vessels from main to subsegmental levels by analyzed thromboembolic materials, and subsequently from vascular remodeling in small unobstructed vessels. Previous studies (43)(44)(45)(46)(47)(48)(49) have reported that improvement in conventional parameters such as CI, 6-MWD, mPAP, and/or PVR showed significant differences between the responder and nonresponder groups, and suggested their usefulness for disease severity assessment and/or treatment response evaluation for CTEPH patients in routine clinical practice. Our results for conventional parameters were comparable with those reported in the past literature for CTEPH patients undergoing drug therapy (43)(44)(45)(46)(47)(48)(49).…”

“…However, our results demonstrated that improvements in CTEPH MRA and PBF showed better correlation with conventional parameters than did improvements in RV/LV diameter ratio, CTEPH CTA , PBV, and MTT. According to several pharmacological reports (43)(44)(45)(46)(47)(48)(49), improvement due to drug therapy is theoretically observed at small vessels in the lung parenchyma and as improved lung peripheral perfusion. Although CTEPH CTA and CTEPH MRA can both qualitatively assess lung parenchyma perfusion, CTEPH MRA is more affected by lung parenchyma perfusion changes than CTEPH CTA because it shows a reduction in perfusion as well as clots in the pulmonary artery.…”

Soluble guanylate cyclase stimulation: an emerging option in pulmonary hypertension therapy

“…There is a clear unmet need for pharmacotherapy in patients with CTEPH, notably those with inoperable CTEPH or persistent post-pulmonary endarterectomy pulmonary hypertension (a review of treatment options for patients with CTEPH can be found in the article by LANG [48] in the present issue of the European Respiratory Review).…”

Update on theEuropean Respiratory Review

“…In the first of these updates, published in March 2009, SOUZA and JARDIM [2] described the results of clinical trials and epidemiological studies in pulmonary arterial hypertension, and called for international collaborations to help standardise the reporting and study of this rare disease, in order to direct future studies and help to delineate their findings. This was complemented by a review on the subject of high-altitude pulmonary hypertension [3] and a series of short reviews of pulmonary hypertension therapies [4][5][6][7]. Following this, GAGA et al [8] provided an update on the epidemiology, clinical assessment, risk factors, pathophysiology and management of severe asthma in June 2009.…”