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Pulmonary arterial hypertension.

Montani D, Günther S, Dorfmüller P, Perros F, Girerd B, Garcia G, Jaïs X, Savale L, Artaud-Macari E, Price LC, Humbert M, Simonneau G, Sitbon O - Orphanet J Rare Dis (2013)

Bottom Line: 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 phosphodiesterase type 5 inhibitors (sildenafil, tadalafil).In addition, currently available specific PAH therapy is discussed as well as future treatments.

View Article: PubMed Central - HTML - PubMed

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 phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). This review discusses the current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH. In addition, currently available specific PAH therapy is discussed as well as future treatments.

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Pathophysiology of PAH. The pulmonary vascular remodeling responsible for PAH is the consequence of closely intertwined predisposing and acquired factors. Thoses pathological elements affect all three layers of precapillary pulmonary arteries leading to intimal hyperplasia, medial thickening and adventitial remodeling/fibrosis. Intra- but also extra-pulmonary cells, such as inflammatory and progenitor cells, are suspected to play a role in this remodeling. This increases right ventricular afterload and consequently results in right ventricular failure.
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Figure 1: Pathophysiology of PAH. The pulmonary vascular remodeling responsible for PAH is the consequence of closely intertwined predisposing and acquired factors. Thoses pathological elements affect all three layers of precapillary pulmonary arteries leading to intimal hyperplasia, medial thickening and adventitial remodeling/fibrosis. Intra- but also extra-pulmonary cells, such as inflammatory and progenitor cells, are suspected to play a role in this remodeling. This increases right ventricular afterload and consequently results in right ventricular failure.

Mentions: PAH is a disease which affects small pulmonary arteries. It is characterized by vascular obstruction leading to progressive increase in vascular resistance. This increases right ventricular afterload and consequently results in right ventricular failure. Intima and media proliferation and its consequent pulmonary vascular obstruction are considered to be the key element in the pathogenesis of PAH. Vasoconstriction, vascular remodeling and thrombosis are factors that increase pulmonary vascular resistance in PAH [107,137]. These processes involve a multitude of cellular and molecular elements (Figure 1).


Pulmonary arterial hypertension.

Montani D, Günther S, Dorfmüller P, Perros F, Girerd B, Garcia G, Jaïs X, Savale L, Artaud-Macari E, Price LC, Humbert M, Simonneau G, Sitbon O - Orphanet J Rare Dis (2013)

Pathophysiology of PAH. The pulmonary vascular remodeling responsible for PAH is the consequence of closely intertwined predisposing and acquired factors. Thoses pathological elements affect all three layers of precapillary pulmonary arteries leading to intimal hyperplasia, medial thickening and adventitial remodeling/fibrosis. Intra- but also extra-pulmonary cells, such as inflammatory and progenitor cells, are suspected to play a role in this remodeling. This increases right ventricular afterload and consequently results in right ventricular failure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750932&req=5

Figure 1: Pathophysiology of PAH. The pulmonary vascular remodeling responsible for PAH is the consequence of closely intertwined predisposing and acquired factors. Thoses pathological elements affect all three layers of precapillary pulmonary arteries leading to intimal hyperplasia, medial thickening and adventitial remodeling/fibrosis. Intra- but also extra-pulmonary cells, such as inflammatory and progenitor cells, are suspected to play a role in this remodeling. This increases right ventricular afterload and consequently results in right ventricular failure.
Mentions: PAH is a disease which affects small pulmonary arteries. It is characterized by vascular obstruction leading to progressive increase in vascular resistance. This increases right ventricular afterload and consequently results in right ventricular failure. Intima and media proliferation and its consequent pulmonary vascular obstruction are considered to be the key element in the pathogenesis of PAH. Vasoconstriction, vascular remodeling and thrombosis are factors that increase pulmonary vascular resistance in PAH [107,137]. These processes involve a multitude of cellular and molecular elements (Figure 1).

Bottom Line: 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 phosphodiesterase type 5 inhibitors (sildenafil, tadalafil).In addition, currently available specific PAH therapy is discussed as well as future treatments.

View Article: PubMed Central - HTML - PubMed

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 phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). This review discusses the current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH. In addition, currently available specific PAH therapy is discussed as well as future treatments.

Show MeSH
Related in: MedlinePlus