Pulmonary Arterial Hypertension Specific Therapy Research Articles

Treatment and Outcome of Pulmonary Arterial Hypertension in HIVInfected Patients: A Review of the Literature

Pulmonary arterial hypertension (PAH) is a life-threatening complication of HIV infection. The prevalence of HIV-associated PAH (HIV-PAH) seems not to be changed over time, regardless of the introduction of highly active antiretroviral therapy (HAART). HIV-PAH treatment is similar to that for all PAH conditions and includes lifestyle modifications, general treatments, and disease-specific treatments. We reviewed the cases of HIV-PAH reported in the Literature in order to evaluate the role of HAART and specific PAH therapy in the prognosis and outcome of HIV-PAH. The research was performed through the PubMed database, by using the following key words: human immunodeficiency virus, AIDS, pulmonary hypertension, antiretroviral, and treatment. The outcome was reported as survival at the end of the observation period of each study. We found 509 patients with HIV-PAH described in the literature to date. At the end of follow-up period, survival rates were 55% and 22% among patients treated or not with antiretroviral therapy (ART), respectively (p = 0.02). Moreover, survival rates at the end of follow-up were 76% and 32% among patients treated or not with specific therapy for PAH (PAH-ST), respectively (p<0.0000001). Survival rates were 69% and 38% among patients treated or not with ART and PAH-ST, respectively (p = 0.02). Specific therapy for PAH should be strongly recommended in patients with HIV-PAH. The role of the HAART in influencing the outcome of HIV-PAH is controversial, even if some evidences seem to indicate a beneficial effect in the clinical course of the disease.

Improvement of HIV-related pulmonary hypertension after the introduction of an antiretroviral therapy: Table 1—

To the Editors: The potential impact of combination antiretroviral therapy (CART) on HIV-related pulmonary arterial hypertension (PAH) remains controversial 1–4. We herein report the case of a dramatic improvement in PAH at the time of the inception of CART in a 19-yr-old female with HIV-1 infection due to mother-to-child transmission. HIV-related PAH was diagnosed in January 2006, when she was stable in stage A2 of the US Centers for Disease Control and Prevention classification without any antiretroviral therapy (table 1⇓). Specific PAH therapy with bosentan was started in January 2006, in combination with oral anticoagulant and diuretic therapy. CART was indicated at that time, but not prescribed owing to patient …

Pulmonary Hypertension in Patients with Chronic Obstructive Pulmonary Disease

Pulmonary hypertension (PH) is an important complication in the natural history of chronic obstructive pulmonary disease (COPD). Its presence is associated with reduced survival and greater use of healthcare resources. The prevalence of PH is high in patients with advanced COPD, whereas in milder forms it might not be present at rest but may develop during exercise. In COPD, PH is usually of moderate severity and progresses slowly, without altering right ventricular function in the majority of patients. Nevertheless, a small subgroup of patients (1-3%) may present with out-of-proportion PH, that is, with pulmonary arterial pressure largely exceeding the severity of airway impairment. These patients depict a clinical picture similar to more severe forms of PH and have higher mortality rates. PH in COPD is caused by the remodelling of pulmonary arteries, which is characterized by the intimal proliferation of poorly differentiated smooth muscle cells and the deposition of elastic and collagen fibres. The sequence of changes that lead to PH in COPD begins at early disease stages by the impairment of endothelial function, which is associated with impaired release of endothelium-derived vasodilating agents (nitric oxide, prostacyclin) and increased expression of growth factors. Products contained in cigarette smoke play a critical role in the initiation of pulmonary endothelial cell alterations. Recognition of PH can be difficult because symptoms due to PH are not easy to differentiate from the clinical picture of COPD. Suspicion of PH should be high if clinical deterioration is not matched by the decline in pulmonary function, and in the presence of profound hypoxaemia or markedly reduced carbon monoxide diffusing capacity. Patients with suspected PH should be evaluated by Doppler echocardiography and, if confirmed, undergo right-heart catheterization in those circumstances where the result of the procedure can determine clinical management. To date, long-term oxygen therapy is the treatment of choice in COPD patients with PH and hypoxaemia because it slows or reverses its progression. Conventional vasodilators are not recommended because of their potential detrimental effects on gas exchange, produced by the inhibition of hypoxic pulmonary vasoconstriction and their lack of effectiveness after long-term treatment. In the subgroup of patients with out-of-proportion PH, new specific therapy available for pulmonary arterial hypertension (PAH) [prostanoids, endothelin-1 receptor antagonists and phosphodiesterase-5 inhibitors] may be considered in the setting of clinical trials. The use of specific PAH therapy in COPD patients with moderate PH is discouraged because of the potential detrimental effect of some of these drugs on gas exchange and there are no data demonstrating their efficacy.

Pulmonary veno-occlusive disease

Pulmonary veno-occlusive disease (PVOD) is currently classified as a subgroup of pulmonary arterial hypertension (PAH) and accounts for 5-10% of cases initially considered to be idiopathic PAH. PVOD has been described as idiopathic or complicating other conditions, including connective tissue diseases, HIV infection, bone marrow transplantation, sarcoidosis and pulmonary Langerhans cell granulomatosis. PVOD shares broadly similar clinical presentation, genetic background and haemodynamic characteristics with PAH. Compared to PAH, PVOD is characterised by a higher male/female ratio, higher tobacco exposure, lower arterial oxygen tension at rest, lower diffusing capacity of the lung for carbon monoxide, and lower oxygen saturation nadir during the 6-min walk test. High-resolution computed tomography (HRCT) of the chest can be suggestive of PVOD in the presence of centrilobular ground-glass opacities, septal lines and lymph node enlargement. Similarly, occult alveolar haemorrhage is associated with PVOD. A noninvasive diagnostic approach using HRCT of the chest, arterial blood gases, pulmonary function tests and bronchoalveolar lavage could be helpful for the detection of PVOD patients and in avoiding high-risk surgical lung biopsy for histological confirmation. PVOD is characterised by a poor prognosis and the possibility of developing severe pulmonary oedema with specific PAH therapy. Lung transplantation is the treatment of choice. Cautious use of specific PAH therapy can, however, be helpful in some patients.

Epoprostenol in pulmonary arterial hypertension

Background: Pulmonary arterial hypertension (PAH) is a devastating disease leading to right heart failure and death in a relatively young patient population. In recent years novel PAH specific therapies have become available. Objective: To determine the place of epoprostenol in current PAH treatment strategies. Methods: An extensive Medline search was performed to evaluate the use of epoprostenol in PAH. Data from both human and animal studies were reviewed. Results/conclusion: Epoprostenol is an effective and potent treatment in pulmonary arterial hypertension and has greatly improved survival, exercise capacity, PAH symptoms, pulmonary haemodynamics and disease progression. A main disadvantage is that it can only be delivered through a continuous intravenous pump infusion.

Review: Therapeutic advances in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis, and vascular remodeling of small pulmonary arteries inducing increased pulmonary arterial resistance. Conventional treatment is based on life style modification and nonspecific treatment (warfarine, diuretics, oxygen). Calcium channel blockers are vasodilatators that have been shown to be of great efficacy in a very specific subpopulation of patients with PAH. For the majority of patients, specific PAH therapies are still lacking. Numerous studies evaluating prostacyclin agonists, endothelin-receptor antagonists, and phosphodiesterase type 5 inhibitors are now available to guide therapeutic choices. Despite those important advances there is still no cure for PAH. Fortunately, research is ongoing and many drugs show promises.

Portopulmonary Hypertension

Portopulmonary hypertension (PoPH) can be defined as elevation of pulmonary arterial pressure and pulmonary vascular resistance in the setting of portal hypertension. Survival results in PoPH are contrasting, and prognostic factors need to be identified. To analyze long-term survival in a large cohort of patients with PoPH with the aim of determining the independent variables affecting survival. We retrospectively analyzed charts of all patients referred to the French Referral Center for pulmonary arterial hypertension with the diagnosis of PoPH between 1984 and 2004. The study population comprised 154 patients; 57% male. Mean age at diagnosis was 49 +/- 11 years, 60% of patients were in New York Heart Association functional class III-IV, and mean 6-minute walk distance was 326 +/- 116 m. Hemodynamic measurements showed a mean pulmonary arterial pressure of 53 +/- 13 mm Hg, cardiac index of 2.9 +/- 0.9 L/min/m(2), and pulmonary vascular resistance of 752 +/- 377 dyn/s/cm(5). Portal hypertension was related to cirrhosis in 136 patients, with a severity assessed as follows: Child-Pugh class A 51%, Child-Pugh class B 38%, Child-Pugh class C 11%. Overall survival rates at 1, 3, and 5 yr were 88, 75, and 68%, respectively. Multivariate regression analysis individualized the presence and severity of cirrhosis and cardiac index as major independent prognostic factors. Prognosis in PoPH is mainly related to the presence and severity of cirrhosis and to cardiac function. The place of pulmonary arterial hypertension-specific therapies remains to be determined in the setting of PoPH.

Endothelin-1/Endothelin-3 Ratio: A Potential Prognostic Factor of Pulmonary Arterial Hypertension

Background:Pulmonary arterial hypertension (PAH) is a rare condition characterized by elevated pulmonary artery pressure leading to right-heart failure and death. Endothelin (ET)-1 has been shown to play a significant pathogenic role in PAH. ET-3 has not yet been investigated in PAH.Methods:ET-1 and ET-3 plasma concentrations were measured in 33 PAH patients prior to any specific PAH therapy and in 9 control subjects. In PAH patients, hemodynamic parameters measured by right-heart catheterization, 6-min walk distance (6MWD), New York Heart Association (NYHA) functional class, and time until lung transplantation or death were recorded.Results:In patients with PAH, levels of ET-1 were increased while those of ET-3 were decreased, as compared to control subjects (p < 0.005 for both comparisons). ET-1/ET-3 ratio varied little in control subjects, while it increased threefold in PAH patients (p < 0.0001). ET-1 correlated positively with right atrial pressure (RAP), indexed total pulmonary resistance, and negatively with cardiac index and venous saturation of oxygen (Svo2). ET-3 correlated positively with 6MWD. ET-1/ET-3 ratio correlated positively with RAP, negatively with Svo2and 6MWD, and was also associated with NYHA functional class. ET-1/ET-3 ratio was associated with prognosis in this sample of PAH patients treated with specific therapies.Conclusions:PAH is characterized by elevated ET-1 and ET-1/ET-3 ratio and decreased ET-3 plasma concentrations. All of them correlate with hemodynamic and clinical markers of disease severity. ET-1/ET-3 ratio might be a novel prognostic factor in PAH. These preliminary data should be validated in a large prospective multicenter cohort of PAH patients.