Early diagnosis is crucial for successful treatment of pulmonary arterial hypertension: 2 cases of late diagnosis (RCD code: II 1A.1)

Treatment of Pulmonary Arterial Hypertension: A Step Forward

Selective Serotonin Reuptake Inhibitors and Pulmonary Arterial Hypertension: A Case-Control Study

The role of calcium channel blockers for the treatment of pulmonary arterial hypertension: How much do we actually know and how could they be positioned today?

Echocardiography in Pulmonary Arterial Hypertension: An Essential Tool

The study of rare diseases is limited by just that, their infrequency. Pulmonary arterial hypertension (PAH), for example, has a prevalence of 15 cases per million.1 Although there has been an explosion in knowledge of and therapies for this life-threatening disease over the past decade, most of our insight is based on small studies. The first therapy that was approved by the Food and Drug Administration in 1995, intravenous epoprostenol, was based on the results of an 81-patient trial.2 The most recently approved therapy, inhaled treprostinil, in 2009, was based on the results of a 235-patient trial.3 Similarly, our understanding of the natural history of this disease is based on small observational series. Articles see pp 156 and 164 To further our comprehension of rare diseases, we often turn to “registries,” constructed as multicenter cohorts of patients who have the disease with longitudinal follow-up. Despite the inherent limitations of their observational and uncontrolled nature, which also represent strengths, these cohorts are useful to describe and compare patient characteristics, practice patterns, and outcomes. Observations from such registries can generate hypotheses that subsequently form the basis of further studies. Lastly, such cohorts facilitate the study of the prognostic profile of the disease via the derivation and validation of clinical prediction tools. In this issue of Circulation , data from the 2 of the most important present-day registries in PAH give us the opportunity to better understand the prognosis of PAH, its determinants, and outcomes in the current treatment era. Humbert and colleagues4 share data from the French National Registry, in which 354 consecutive idiopathic, heritable, and anorexigen-associated patients with PAH were enrolled from October 2002 to October 2003. They report 1-, 2-, and 3-year survival rates of 82.9%, 67.1%, and 58.2%, respectively. Sadly, despite the many advances in …

<i>Circulation</i> Editors’ Picks

COUNTERPOINT: Did the World Symposium on Pulmonary Hypertension Get It Right in Redefining Abnormal Pulmonary Arterial Pressure? No

Pulmonary arterial hypertension symptoms in systemic lupus erythematosus patients are non-specific and early diagnosis and intervention are challenging. It remains essential to explore risk factors for pulmonary arterial hypertension in systemic lupus erythematosus patients to identify high risk patients and allow intensive monitoring. From January 2010 to December 2018, 84 patients with systemic lupus erythematosus and pulmonary arterial hypertension and 160 patients with systemic lupus erythematosus but without pulmonary arterial hypertension were enrolled. Clinical manifestations and laboratory test results were compared between the two groups to identify predictors of pulmonary arterial hypertension. Candidate pulmonary arterial hypertension risk factors were further compared among systemic lupus erythematosus-pulmonary arterial hypertension patients with different characteristics. Among collected patient characteristics, Raynaud's phenomenon (OR 2.32, 95% CI: 1.17-4.61), digital vasculitis (OR 4.12, 95% CI: 1.48-11.49), pericardial effusion, pulmonary interstitial lesions, positive anti-u1 ribonucleoprotein antibodies, and positive anticardiolipin antibodies immunoglobulin G were associated with significantly higher risk of pulmonary arterial hypertension in systemic lupus erythematosus patients. Among these candidate risk factors, positive anti-u1 ribonucleoprotein antibody was independently associated with severe pulmonary arterial hypertension and more active disease. Digital vasculitis was independently associated with systemic lupus erythematosus alleviation, while pericardial effusion was associated with systemic lupus erythematosus deterioration. Pericardial effusion was associated with longer pulmonary arterial hypertension duration. The significant association between studied clinical and laboratory indicators and risk of pulmonary arterial hypertension, pulmonary arterial hypertension and systemic lupus erythematosus characteristics suggested that these factors can be used to identify patients at higher risk of pulmonary arterial hypertension and adverse outcomes. Close monitoring may be indicated in patients with these risk factors, especially with more than one risk factor.

Pulmonary arterial hypertension is a life-threatening disorder that refers to a group of diseases characterized by an abnormal elevation of the blood pressure within the pulmonary circulation due to a vasculopathy of the pulmonary microcirculation (1). If left untreated, the overall prognosis of pulmonary arterial hypertension is poor, with a 5-year survival rate of 34%. The most common cause of death is progressive right-sided heart failure (2). There is no pharmacologic cure for pulmonary arterial hypertension, and a team approach is required for the proper care of these patients (3). Treatment is directed at improving clinical symptoms, increasing exercise tolerance and extending survival. Until just a few years ago, standard treatment options for the treatment of pulmonary arterial hypertension were limited and included coumarin derivatives, calcium channel blockers, diuretics, digoxin and oxygen supplementation (4). In the last decade, the therapeutic options for pulmonary arterial hypertension have made considerable advances. In at least three major randomized controlled trials, the continuous intravenous infusion of epoprostenol, a synthetic salt of prostacyclin with potent vasodilatory ability, has been shown to improve exercise tolerance, hemodynamics, survival and quality of life in patients with New York Heart Association (NYHA) functional classes III and IV with either primary pulmonary hypertension or pulmonary arterial hypertension associated with scleroderma (5-9). Epoprostenol has now become a mainstay therapy in the long-term treatment of primary pulmonary hypertension or pulmonary arterial hypertension associated with scleroderma. Nevertheless, epoprostenol is far from an ideal form of therapy. Issues such as the short half-life of the drug, need for continuous central intravenous access and significant side effects have led to the development of more stable prostacyclin analogues as alternative therapies for primary pulmonary hypertension. These alternative therapies include iloprost (inhaled delivery) and treprostinil (subcutaneous delivery). As a result, the Food and Drug Administration (FDA) recently approved treprostinil for the treatment of pulmonary arterial hypertension in patients with NYHA classes II-IV. This review will offer a discussion of the basic pharmacology of treprostinil, its similarities to and differences from epoprostenol, the animal studies as well as the initial investigational studies leading to its FDA approval, and clinical uses of the drug alone or in combination with newer therapies directed at pulmonary arterial hypertension developed over the last decade.

Pulmonary Hypertension: From an Orphan Disease to a Public Health Problem

COMPARISON BETWEEN PULMONARY ARTERIAL HYPERTENSION (PAH) RISK ASSESSMENT METHODS, INCLUDING PULMONARY HYPERTENSION OUTCOME RISKS ASSESSMENT (PHORA)

A Novel Vascular Homing Peptide Strategy to Selectively Enhance Pulmonary Drug Efficacy in Pulmonary Arterial Hypertension

Evidence for the use of combination targeted therapeutic approaches for the management of pulmonary arterial hypertension

To review the pharmacologic treatment options for pulmonary arterial hypertension in the cardiac intensive care setting and summarize the most-recent literature supporting these therapies. Literature search for prospective studies, retrospective analyses, and case reports evaluating the safety and efficacy of pulmonary arterial hypertension therapies. Mechanisms of action and pharmacokinetics, treatment recommendations, safety considerations, and outcomes for specific medical therapies. Specific targeted therapies developed for the treatment of adult patients with pulmonary arterial hypertension have been applied for the benefit of children with pulmonary arterial hypertension. With the exception of inhaled nitric oxide, there are no pulmonary arterial hypertension medications approved for children in the United States by the Food and Drug Administration. Unfortunately, data on treatment strategies in children with pulmonary arterial hypertension are limited by the small number of randomized controlled clinical trials evaluating the safety and efficacy of specific treatments. The treatment options for pulmonary arterial hypertension in children focus on endothelial-based pathways. Calcium channel blockers are recommended for use in a very small, select group of children who are responsive to vasoreactivity testing at cardiac catheterization. Phosphodiesterase type 5 inhibitor therapy is the most-commonly recommended oral treatment option in children with pulmonary arterial hypertension. Prostacyclins provide adjunctive therapy for the treatment of pulmonary arterial hypertension as infusions (IV and subcutaneous) and inhalation agents. Inhaled nitric oxide is the first-line vasodilator therapy in persistent pulmonary hypertension of the newborn and is commonly used in the treatment of pulmonary arterial hypertension in the ICU. Endothelin receptor antagonists have been shown to improve exercise tolerance and survival in adult patients with pulmonary arterial hypertension. Soluble guanylate cyclase stimulators are the first drug class to be Food and Drug Administration approved for the treatment of chronic thromboembolic pulmonary hypertension. Literature and data supporting the safe and effective use of pulmonary arterial hypertension therapies in children in the cardiac intensive care are limited. Extrapolation of adult data has afforded safe medical treatment of pulmonary hypertension in children. Large multicenter trials are needed in the search for safe and effective therapy of pulmonary hypertension in children.

This article aims to review recent advances in the diagnosis and treatment of pulmonary arterial hypertension in neonates and children with congenital heart disease. Articles on pulmonary arterial hypertension in congenital heart disease were retrieved from PubMed and MEDLINE published after 1958. A diagnosis of primary (or idiopathic) pulmonary arterial hypertension is made when no known risk factor is identified. Pulmonary arterial hypertension associated with congenital heart disease constitutes a heterogenous group of conditions and has been characterized by congenital systemic-to-pulmonary shunts. Despite the similarities in histologic appearance of pulmonary vascular disease, there are differences between pulmonary arterial hypertension secondary to congenital systemic-to-pulmonary shunts and those with other conditions with respect to pathophysiology, therapeutic strategies, and prognosis. Revision and subclassification within the category of secondary pulmonary arterial hypertension based on pathophysiology were conducted to improve specific treatments. The timing of surgical repair is crucial to prevent and minimize risk of postoperative pulmonary arterial hypertension. Drug therapies including prostacyclin, endothelin-receptor antagonist, phosphodiesterase inhibitor, and nitric oxide have been evolved with promising results in neonates and children. Among the different forms of congenital heart diseases, an early correction generally prevents subsequent development of pulmonary arterial hypertension. Emerging therapies for treatment of patients with idiopathic pulmonary arterial hypertension also improve quality of life and survival in neonates and children with congenital heart disease associated with pulmonary arterial hypertension. Heart and lung transplantation or lung transplantation in combination with repair of the underlying cardiac defect is a therapeutic option in a minority of patients. Partial repair options are also beneficial in some selected cases. Randomized controlled trials are needed to evaluate the safety and efficacy of these therapies including survival and long-term outcome.