Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome (HPS) are rare pulmonary vascular complications of portal hypertension [1]. In PoPH, pulmonary vascular resistance (PVR) is elevated, resulting in heightened right ventricular workload which may lead to right-sided heart failure. HPS is characterised by progressive hypoxaemia due to diffusion–perfusion mismatching caused by regional, mostly basilar, intrapulmonary vascular dilatations of capillary and pre-capillary vessels. The exact pathogenesis of both conditions is unclear, as is the underlying predisposition causing a small proportion of patients with liver disease to develop PoPH or HPS. Patients with portopulmonary hypertension may develop hepatopulmonary syndrome during treatment with pulmonary vasodilators
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but life-threatening disease resulting from unresolved thromboembolic obstructions. Pulmonary endarterectomy (PEA) surgery is the gold-standard treatment as it is potentially curative; however, not all patients are deemed operable and up to one-third have persistent or recurrent CTEPH after the procedure. Pulmonary arterial hypertension (PAH) and CTEPH have similar clinical presentations and histopathological features, so agents shown to be effective in PAH have often been prescribed to patients with CTEPH in the absence of proven therapies. However, clinical evidence for this strategy is not compelling. A number of small uncontrolled trials have investigated endothelin receptor antagonists, prostacyclin analogues and phosphodiesterase type 5 inhibitors in CTEPH with mixed results, and a phase III study of the endothelin receptor antagonist bosentan met only one of its two co-primary end-points. Recently, however, the soluble guanylate cyclase stimulator, riociguat, was approved in the USA and Europe for the treatment of inoperable or persistent/recurrent CTEPH following positive results from the phase III CHEST study (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial). This article reviews the current evidence for the use of pharmacological therapies in CTEPH.
BackgroundRegular risk assessment is recommended in pulmonary arterial hypertension (PAH) management to improve patient outcomes. The REVEAL risk score (RRS) predicts survival in patients with PAH, including those from the PATENT study, which assessed riociguat, a soluble guanylate cyclase stimulator approved for PAH treatment. An updated version, RRS 2.0, has been developed to further refine risk prediction.MethodsThis post hoc analysis of PATENT-1 and its open-label extension PATENT-2 (n = 396) assessed RRS 2.0 score and risk stratum and their association with survival and clinical worsening-free survival (CWFS).ResultsAt PATENT-1 Week 12, riociguat improved RRS 2.0 versus placebo (least-squares mean difference versus placebo: −1.0 [95% confidence interval − 1.4 to −0.6; p < 0.0001]) and more patients improved risk stratum with riociguat (57%) versus placebo (42%). These improvements were maintained at PATENT-2 Week 12. RRS 2.0 score and risk strata at PATENT-1 baseline and Week 12 were significantly associated with survival and CWFS in PATENT-2 (p < 0.0001); change in RRS 2.0 score from PATENT-1 baseline to Week 12 was also significantly associated with outcomes.ConclusionsThese data suggest that RRS 2.0 has clinical utility in predicting long-term outcomes and monitoring treatment response in patients with PAH.
The current treatment of patients with pulmonary arterial hypertension (PAH) is founded on repeated risk stratification at diagnosis and during follow-up. The 2015 European pulmonary hypertension guidelines propose a multidimensional risk assessment strategy based on nine items and 13 distinct variables in order to predict the estimated 1-year mortality [1, 2]. Recently, several large registry studies have shown that simplified tools can be used to predict outcomes and guide treatment decisions [3–6]. These studies have focused largely on 6-min walking distance (6MWD), World Health Organization (WHO) functional class (FC), right atrial pressure (RAP), cardiac index (CI) and brain natriuretic peptides (BNP or NT-proBNP). Low-risk criteria were defined as WHO FC I or II, 6MWD >440 m, RAP <8 mmHg, CI ≥2.5 L·min−1·m−2, BNP <50 ng·L−1 and NT-proBNP <300 ng·L−1. Risk stratification was based either on the average risk or the number of low-risk criteria. A unanimous finding of all these studies, irrespective of the assessment strategy, was that risk stratification at follow-up, i.e. in patients receiving PAH treatment, provided more accurate predictions of outcome than the initial risk assessment at the time of diagnosis [3–5, 7]. In addition, a noninvasive approach based solely on 6MWD, FC and BNP/NT-proBNP during follow-up was particular useful for identifying patients with a very low mortality risk (≤5% over a 5-year observation period) [4, 8]. Of note, these data were derived mainly from patients with idiopathic PAH (IPAH) and there was limited evidence that the same risk assessment strategy can be used in patients with other forms of PAH, including those with PAH due to systemic sclerosis (SSc). An abbreviated version of the ESC/ERS risk stratification strategy predicts outcome in patients with systemic sclerosis and pulmonary arterial hypertension
Extracorporeal membrane oxygenation (ECMO) may be justified in immunocompromised patients with Pneumocystis-associated acute respiratory distress syndrome, and an awake ECMO strategy might be feasible in selected patientshttp://bit.ly/2YFyrOK
Hintergrund Eine geringe Diffusionsbarriere ist essentiell für die Funktion des pulmonalen Gasaustausches. Sowohl bei der alveolären kapillären Dysplasie (ACD) als auch bei der nicht-spezifischen interstitiellen Pneumonie (NSIP) ist diese Funktion kompromittiert durch einen Gewebsumbau an der Schnittstelle von Alveole und Kapillare. Eine direkte molekulare Gegenüberstellung dieser beiden Erkrankungen ist bislang nicht erfolgt.
Risk stratification has gained an increasing role in predicting outcomes and guiding the treatment of patients with pulmonary arterial hypertension (PAH). The most predictive prognostic factors are three noninvasive parameters (World Health Organization functional class, 6-min walk distance and natriuretic peptides) that are included in all currently validated risk stratification tools. However, suffering from limitations mainly related to reduced specificity of PAH severity, these variables may not always be adequate in isolation for guiding individualised treatment decisions. Moreover, with effective combination treatment regimens and emerging PAH therapies, markers associated with pulmonary vascular remodelling are expected to become of increasing relevance in guiding the treatment of patients with PAH. While reaching a low mortality risk, assessed with a validated risk tool, remains an important treatment goal, preliminary data suggest that invasive haemodynamics and cardiac imaging may add incremental value in guiding treatment decisions.
