Pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role, essentially in the screening proposing criteria for estimating the presence of PH mainly based on tricuspid regurgitation peak velocity and systolic artery pressure (sPAP). The therapy of PAH consists of non-specific drugs including oral anticoagulation and diuretics as well as PAH specific therapy. Diuretics are one of the most important treatment in the setting of PH because right heart failure leads to fluid retention, hepatic congestion, ascites and peripheral edema. Current recommendations propose oral anticoagulation aiming for targeting an International Normalized Ratio (INR) between 1.5-2.5. Target INR for patients displaying chronic thromboembolic PH is between 2–3. Better understanding in pathophysiological mechanisms of PH over the past quarter of a century has led to the development of medical therapeutics, even though no cure for PAH exists. Several specific therapeutic agents were developed for the medical management of PAH including prostanoids (epoprostenol, trepoprostenil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan) and phosph...

Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives

“…Pulmonary arterial hypertension (PAH) describes a subpopulation of patients with PH that are characterised haemodynamically by the presence of pre-capillary PH. Idiopathic PAH (IPAH) is a sporadic disease and one of the most common forms of PAH, with neither a family history of PAH nor an identified risk factor [2]. Germline mutations in the gene encoding bone morphogenetic protein receptor type-2 (BMPR2) are a major predisposing genetic factor among heritable PAH (HPAH) cases, which segregate in an autosomal dominant pattern, with markedly reduced penetrance [2][3][4].…”

“…Idiopathic PAH (IPAH) is a sporadic disease and one of the most common forms of PAH, with neither a family history of PAH nor an identified risk factor [2]. Germline mutations in the gene encoding bone morphogenetic protein receptor type-2 (BMPR2) are a major predisposing genetic factor among heritable PAH (HPAH) cases, which segregate in an autosomal dominant pattern, with markedly reduced penetrance [2][3][4]. Several new loci harbouring mutations among patients with and without familial PAH were recently identified through genome-wide association studies and whole-exome sequencing [2,3].…”

Modafinil improves monocrotaline-induced pulmonary hypertension rat model

“…ulmonary arterial hypertension (PAH) is a refractory disease and all occurrences of PAH exhibit increased pulmonary vascular resistance and pulmonary vascular remodeling (1,2). The disease is a progressive condition characterized by elevated pulmonary arterial pressures leading to right ventricular failure (3).…”

“…Calcium channel blocker induces vasodilation through the decrease in intracellular calcium concentration (1). ET receptor antagonist has vasodilation and anti-proliferative properties but it is expensive.…”

Clinical characteristics and risk factors of pulmonary hypertension associated with chronic respiratory diseases: a retrospective study

“…Significant progress has been made in understanding the epidemiology, clinical characteristics and prognosis of PH in recent years (3)(4)(5)(6)(7). So far, most of the studies regarding PH focused on idiopathic PH, chronic thromboembolic PH (CTEPH), PH associated with congenital heart disease and with connective tissue disease; PH associated with chronic respiratory disease was usually despised or neglected, although it is also an essential subtype of PH (8).…”