Clinics in chest medicine
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Clinics in chest medicine · Dec 2013
ReviewNovel medical therapies for pulmonary arterial hypertension.
Available targeted therapies for pulmonary arterial hypertension are capable only of slowing progression of the disease and a cure remains elusive. However with the improved understanding of the pulmonary vascular remodeling that characterizes the disease, there is optimism that the disconnect between preclinical and clinical studies may be bridged with some of the newer therapies that are now at different stages of clinical evaluation. This article examines the evidence behind these new candidate treatments that may become part of the arsenal available for clinicians managing this devastating disease.
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Despite major advances in understanding the mechanisms of disease and development of specific drug therapy, pulmonary arterial hypertension (PAH) remains a progressive, fatal disease. At present there are 3 classes of drug therapy for PAH: prostaglandins, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. ⋯ This review presents a detailed account of the published data on the use of combination therapy in PAH. There are few randomized, placebo-controlled trial data to strongly support efficacy of most combination therapy, particularly oral combination therapy.
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The pathology of pulmonary hypertension includes numerous abnormalities of the intima, media, and adventitia of the pulmonary vascular tree. A recently completed systematic analysis revealed high variability of morphologic measurements within a given pulmonary arterial hypertension (PAH) lung and among all PAH lungs, as well as distinct pathologic subphenotypes, and included a subset of lungs lacking intimal and medial remodeling. There was correlation between perivascular inflammation, remodeling, and hemodynamics. This article summarizes the pathologic features of the normal and abnormal pulmonary circulation, and correlations with animal models.
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Painstaking research led to the discovery of gene mutations responsible for heritable forms of pulmonary arterial hypertension (PAH). Mutations in the gene BMPR2, which codes for a cell surface receptor (BMPRII), cause the approximately 80% of heritable cases of PAH. ⋯ Other family members of many patients diagnosed with idiopathic PAH may be diagnosed with PAH. Genetic counseling and testing should be offered to patients diagnosed with heritable or idiopathic PAH.
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The relationship between pulmonary hypertension and left heart disease is complex. When initial assessment suggests the presence of pulmonary hypertension, it is critical to determine its precise nature: pulmonary arterial hypertension versus pulmonary hypertension owing to left heart disease. ⋯ Treatment requires optimal therapy of the underlying left heart disease. It is uncertain whether therapies for pulmonary arterial hypertension have any role in treating pulmonary hypertension owing to left heart disease, and there are safety concerns with these agents in this population.