Treatment of Severe Pulmonary Hypertension Secondary to Connective Tissue Diseases With Continuous IV Epoprostenol (Prostacyclin)

To investigate the effects of combined medication of nifedipine and magnesium sulfate on the blood pressure, pregnancy-associated plasma protein A (PAPP-A), vascular endothelial growth factor (VEGF), nitric oxide (NO), homocysteine (Hcy) and von Willebrand factor (vWF) in gestational hypertension patients.

A total of 220 gestational hypertension patients were enrolled as the subjects, and divided into two groups randomly, i.e. the observation group and the control group. In observation group, patients took combined medication of nifedipine and magnesium sulfate, while those in the control group only took magnesium sulfate for treatment. Clinical efficacy, and the changes in blood pressure, PAPP-A, VEGF, NO, Hcy and vWF before and after treatment were compared between two groups.

In the observation group and the control group, total effectiveness rates were 92.7% and 70.9%, respectively (p < 0.05). After treatment, we found significant decreases in PAPP-A, VEGF, NO, Hcy and vWF in patients of two groups, with more significant decreases in the observation group (p < 0.05). Incidence rates of the adverse reactions in two groups were 5.5% and 6.4%, respectively, without any statistically significant differences (p > 0.05). In the observation group, patients had fewer complications (p < 0.05).

Combined medication of magnesium sulfate and nifedipine can decrease the levels of PAPP-A, VEGF, NO, Hcy and vWF in serum as well as the blood pressure of patients with gestational hypertension, with a reduction in incidence rate of complications and improvement in efficacy.

Major advances have been made in the treatment of World Health Organization Group 1 pulmonary arterial hypertension (PAH). Since the mid-1990s, nine medications have become available in the United States to target three key pathophysiologic derangements in PAH – the prostacyclin, endothelin, and nitric oxide pathways. As a group, these agents have led to improvements in functional capacity, symptoms, hemodynamics, and survival. Most patients with mild to moderate PAH are started on orally active agents such as endothelin receptor antagonists or phosphodiesterase inhibitors. Patients with more severe disease, particularly those with evidence of right heart failure, should be treated with continuous prostacyclin infusion or a combination of a prostacyclin and oral therapy. Each medication has unique properties and clinical considerations, and the selection of an appropriate therapy must be tailored to the individual patient. None of the currently available WHO Group 1 PAH therapies are curative, however, and it is the hope that new therapies in development may halt or reverse disease progression. This review will discuss the major therapeutic classes of presently available medications and their role in managing the patient with PAH. We will also review data supporting the use of combination therapy, adjuvant background therapy, and new agents currently under investigation.

To discuss the clinical subtypes, pathogenesis, pathology, diagnostic evaluation, treatment options, and prognosis of pulmonary hypertension in systemic sclerosis (SSc-PH) and highlight its fundamental differences from idiopathic pulmonary arterial hypertension (IPAH).

A Medline search for articles published between January 1969 and June 2010 was conducted using the following keywords: scleroderma, systemic sclerosis, pulmonary hypertension, pulmonary arterial hypertension, pulmonary veno-occlusive disease, pathogenesis, pathology, investigation, treatment, and prognosis. The essential differences from IPAH in pathogenesis and histopathologic findings were highlighted and the limitations of some of the investigations used were emphasized. The differences in response to currently accepted therapy and prognosis were also reviewed.

In scleroderma, pulmonary hypertension can be present in isolation or along with interstitial lung disease and left heart disease. In SSc-PH, the unique histopathologic findings in the lungs include intimal fibrosis, absence of plexiform lesions, and a high prevalence of pulmonary veno-occlusive disease-like lesions. Both “6-minute walk test” and NT-proBNP have their limitations in the evaluation of SSc-PH. For treatment, calcium channel blockers are ineffective and anticoagulation should be used with caution. Currently approved therapies are not as effective and prognosis is much worse in SSc-PH compared with IPAH.

SSc-PH is a complex condition with poorer response to therapy and worse outcome compared with that of IPAH. Recent findings have shed some light about the pathophysiology and pathogenesis of SSc-PH. Further research in this area is warranted to better understand the complex pathogenesis and devise better therapeutic strategies.

Systemic lupus erythematosus (SLE) is a rare complex autoimmune disease with a multisystem involvement. The clinical manifestations of this disease include an erythematous rash, oral ulcers, polyarthralgia, nonerosive arthritis, polyserositis, hematologic, renal, neurologic, pulmonary and cardiac abnormalties. The involvement of the respiratory system is frequent. Pleuro-pulmonary manifestations are present in almost half of the patients during the disease course and may be the presenting symptoms in 4–5% of patients with SLE. Complications directly associated to the disease include pleuritis with or without pleural effusion, alveolitis, interstitial lung disease, lupus pneumonitis, pulmonary hemorrhage, pulmonary arterial hypertension, and pulmonary thromboembolic disease. Complications due to secondary causes include pleuro-pulmonary manifestations of cardiac and renal failure, atelectasis due to diaphragmatic dysfunction, opportunistic pneumonia, and drug toxicity. The prevalence, clinical presentation, prognosis and response to treatment vary, depending on the pattern of involvement. As with other connective tissue diseases, early and specific therapeutic intervention may be indicated for many of these pleuro-pulmonary manifestations.

Most cases of pulmonary arterial hypertension (PAH) are not idiopathic, but rather are attributable to other disorders. This fact has become increasingly apparent following the recent establishment of centralised PAH registries in several countries. Yet, this “secondary” PAH has been the subject of even less research than idiopathic PAH, itself an orphan disease par excellence. Secondary PAH is heterogeneous: prognosis and response to vasodilator therapy differs substantially between various forms of secondary PAH, partly as a function of underlying pathophysiology, and cannot simply be extrapolated from data derived from idiopathic PAH.

This article reviews the commonest secondary causes of PAH, focusing on epidemiology, risk factors, clinical presentation, treatment options, prognosis, and the role of screening. PAH secondary to chronic hypoxia, congenital heart disease, connective tissue disorders, liver disease, appetite suppressants and stimulants, and HIV infection are all considered. Strengths and limitations of available screening tests for PAH are discussed.