Pulmonary arterial hypertension (PAH) is a clinical condition characterized by the presence of pre-capillary PH and pulmonary vascular resistance >3 Wood units, in the absence of other causes of pre-capillary PH. PAH prognosis is still poor with a median survival of 7 years. As a rare disease the European Union encourages research and gives priority founding on this field. Our Center is currently one of the most important Italian centers for PAH; it's the Reference Center for rare disease (idiopathic PAH) in the Lazio Region. Hypoxaemia is a frequent finding in patients with PAH and could be related to ventilation-perfusion mismatch, reduced diffusing capacity, decreased cardiac output or the opening of intrapulmonary (IP) or intracardiac shunt. Hypoxemia in PAH is one of the main determinants of exercise tolerance and prognosis. Desaturation during 6MWT is associated with a 2.9 relative mortality risk of in PAH. The most relevant and international registries consider more than 70% of all patients with PAH at the intermediate risk with an heterogenetic treatment response and a significant different mortality rate. Hypoxemia related to IP shunt is not included in the major PH international registries, mainly because of its complicated assessment. We want to conduct an observational and prospective study enrolling 50 consecutive PAH patients and following them for 12 months. A right heart catheterization will be performed at baseline and while breathing 100% oxygen for at least 10-15 minutes to calculate shunt fraction with the formula (Cc - Ca)/(Cc - Cv). A physician of our Center will perform follow-up visits every 3-6 months in order to detect an early clinical worsening. The inclusion of IP shunt in the risk scores may allow clinicians to better stratify patients at intermediate risk and to identify patients who need an earlier aggressive strategies such as lung transplantation.
Despite the availability over the past 20 years of multiple drugs, pulmonary arterial hypertension (PAH) remains a severe clinical condition [1]. Assessing the prognosis is an important part of care of patients with PAH and includes clinical, functional, exercise, non-invasive and invasive variables. One of the main limitation of the existing scores is that 70% of the patients is at intermediate risk and that, despite the same risk profile, patients show an heterogenous treatment response and mortality rate [2-5].
Aim of the present study is to better understand the role of IP right to left shunt-induced hypoxia on clinical conditions and prognosis in PAH. Hypoxemia in PAH is one of the main determinants of exercise tolerance and prognosis. Indeed 10% of desaturation during 6MWT is associated with a 2.9 relative mortality risk of in PAH [6]. In precapillary PH, mild to moderate hypoxemia is common in [7] and is multifactorial, related to ventilation/perfusion mismatch [8], low diffusion capacity and low mixed venous PO2 due to decreased cardiac output [9]. In case of more severe hypoxemia, alternative diseases such as pulmonary veno-occlusive disease, distal thromboembolic disease, interstitial lung disease should be excluded. [10]. True right-to-left (RL) shunting is classically considered an intracardiac shunt due to congenital heart disease or reopening of patent foramen ovale [11]. Further studies have demonstrated that many PAH patients have RL shunting caused by IP arteriovenous pathways recruited with increase in microvascular pressure, similar to mechanisms seen during physiological exercise [12,13].
2015 ESC/ERS Guidelines recommend continuous long-term O2 in PAH patients when arterial blood pressure is consistently
A better knowledge of IP shunt role in causing hypoxia in PAH patients could allow to better stratify the risk of patients at the intermediate risk, adopting more aggressive treatment strategies and including patients in the waiting list for lung transplantation at earlier stage of the disease. .
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