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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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Pulmonary arteries of the muscular type displaying obstructive arteriopathy in lungs of patients with PAH. A Medial hypertrophy with smooth muscle cell proliferation and pronounced adventitial fibrosis. Magnification x200, Weigert-hematoxylin-phloxine-saffron staining (WHPS). B Concentric non-laminar intimal fibrosis comprising numerous myofibroblasts (arrows). C Eccentric intimal fibrosis corresponding to organized thrombotic material. Br: bronchus, Ar: pulmonary artery. Magnification x100, HES staining. D Thrombotic lesion, so called "colander-like lesion", with partial recanalization by microvessels. Note the similarity to plexiform lesions (F). Magnification x100, HES. E Concentric laminar intimal fibrosis, so called „onion-skin lesion“. Magnification × 200, HES. F Plexiform lesion with proliferation of small sinusoid-like vessels on a fibrotic matrix. Note surrounding dilated vessels. Magnification x100, HES. G Multiple dilation lesions being the sentinel of the centrally located plexiform lesion. Magnification × 40, Elastica-van-Gieson staining (EvG). H The same plexiform lesion after immunohistochemical staining with anti-CD3, a T-lymphocytic marker. Note the perivascular distribution of the inflammatory infiltrate. Magnification x100.
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Figure 2: Pulmonary arteries of the muscular type displaying obstructive arteriopathy in lungs of patients with PAH. A Medial hypertrophy with smooth muscle cell proliferation and pronounced adventitial fibrosis. Magnification x200, Weigert-hematoxylin-phloxine-saffron staining (WHPS). B Concentric non-laminar intimal fibrosis comprising numerous myofibroblasts (arrows). C Eccentric intimal fibrosis corresponding to organized thrombotic material. Br: bronchus, Ar: pulmonary artery. Magnification x100, HES staining. D Thrombotic lesion, so called "colander-like lesion", with partial recanalization by microvessels. Note the similarity to plexiform lesions (F). Magnification x100, HES. E Concentric laminar intimal fibrosis, so called „onion-skin lesion“. Magnification × 200, HES. F Plexiform lesion with proliferation of small sinusoid-like vessels on a fibrotic matrix. Note surrounding dilated vessels. Magnification x100, HES. G Multiple dilation lesions being the sentinel of the centrally located plexiform lesion. Magnification × 40, Elastica-van-Gieson staining (EvG). H The same plexiform lesion after immunohistochemical staining with anti-CD3, a T-lymphocytic marker. Note the perivascular distribution of the inflammatory infiltrate. Magnification x100.

Mentions: This abnormality of the vessel wall can be observed in all subgroups of PAH and may even be encountered in other forms of PH, e.g. in mitral valve stenosis. The lesion corresponds to a smooth muscle cell proliferation and / or recruitment within the tunica media; the histological criterion of hypertrophy / hyperplasia is fulfilled, when the diameter of a single medial layer, delimited by its internal and external elastic lamina, exceeds 10 per cent of the arteries cross-sectional diameter (Figure 2A). Isolated hypertrophy of the medial layer may be considered as an early and even reversible event as it has been shown in PH due to hypoxia in high altitude [171]. However, medial hypertrophy is usually associated with other PAH-lesions.


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)

Pulmonary arteries of the muscular type displaying obstructive arteriopathy in lungs of patients with PAH. A Medial hypertrophy with smooth muscle cell proliferation and pronounced adventitial fibrosis. Magnification x200, Weigert-hematoxylin-phloxine-saffron staining (WHPS). B Concentric non-laminar intimal fibrosis comprising numerous myofibroblasts (arrows). C Eccentric intimal fibrosis corresponding to organized thrombotic material. Br: bronchus, Ar: pulmonary artery. Magnification x100, HES staining. D Thrombotic lesion, so called "colander-like lesion", with partial recanalization by microvessels. Note the similarity to plexiform lesions (F). Magnification x100, HES. E Concentric laminar intimal fibrosis, so called „onion-skin lesion“. Magnification × 200, HES. F Plexiform lesion with proliferation of small sinusoid-like vessels on a fibrotic matrix. Note surrounding dilated vessels. Magnification x100, HES. G Multiple dilation lesions being the sentinel of the centrally located plexiform lesion. Magnification × 40, Elastica-van-Gieson staining (EvG). H The same plexiform lesion after immunohistochemical staining with anti-CD3, a T-lymphocytic marker. Note the perivascular distribution of the inflammatory infiltrate. Magnification x100.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Pulmonary arteries of the muscular type displaying obstructive arteriopathy in lungs of patients with PAH. A Medial hypertrophy with smooth muscle cell proliferation and pronounced adventitial fibrosis. Magnification x200, Weigert-hematoxylin-phloxine-saffron staining (WHPS). B Concentric non-laminar intimal fibrosis comprising numerous myofibroblasts (arrows). C Eccentric intimal fibrosis corresponding to organized thrombotic material. Br: bronchus, Ar: pulmonary artery. Magnification x100, HES staining. D Thrombotic lesion, so called "colander-like lesion", with partial recanalization by microvessels. Note the similarity to plexiform lesions (F). Magnification x100, HES. E Concentric laminar intimal fibrosis, so called „onion-skin lesion“. Magnification × 200, HES. F Plexiform lesion with proliferation of small sinusoid-like vessels on a fibrotic matrix. Note surrounding dilated vessels. Magnification x100, HES. G Multiple dilation lesions being the sentinel of the centrally located plexiform lesion. Magnification × 40, Elastica-van-Gieson staining (EvG). H The same plexiform lesion after immunohistochemical staining with anti-CD3, a T-lymphocytic marker. Note the perivascular distribution of the inflammatory infiltrate. Magnification x100.
Mentions: This abnormality of the vessel wall can be observed in all subgroups of PAH and may even be encountered in other forms of PH, e.g. in mitral valve stenosis. The lesion corresponds to a smooth muscle cell proliferation and / or recruitment within the tunica media; the histological criterion of hypertrophy / hyperplasia is fulfilled, when the diameter of a single medial layer, delimited by its internal and external elastic lamina, exceeds 10 per cent of the arteries cross-sectional diameter (Figure 2A). Isolated hypertrophy of the medial layer may be considered as an early and even reversible event as it has been shown in PH due to hypoxia in high altitude [171]. However, medial hypertrophy is usually associated with other PAH-lesions.

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