Contemporary Management of Pulmonary Arterial HTN Improves Outcomes

By Will Boggs MD

November 22, 2016

NEW YORK (Reuters Health) - Current evidence-based management of pulmonary arterial hypertension (PAH) is associated with improved survival and reduced hospitalization rates, according to two separate papers.

"In contrast to the original PAH experience, the contemporary approach to this disease is based on sound basic science and clinical trial data that is sizeable," Dr. Bradley A. Maron from Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts told Reuters Health by email. "Today PAH is treatable, and clinical care strives to achieve a high benchmark of success, including remediation of symptoms."

Dr. Maron and Dr. Nazzareno Galie from University of Bologna, Italy review the contemporary approach to PAH diagnosis, management, and treatment in their November 16th JAMA Cardiology online report.

The diagnosis of PAH is based on a mean pulmonary artery pressure of at least 25 mmHg during resting supine right heart catheterization after exclusion of comorbid cardiac, parenchymal lung, thromboembolic, and other diseases that predispose to abnormal cardiopulmonary hemodynamics.

The reported prevalence of PAH, 5 to 25 cases per 1 million persons, is based on registry studies and is likely to underestimate the true rate of the disease, they say.

As many as 85% of at-risk patients receive an inappropriate, incomplete, and delayed diagnosis of PAH, with the average patient having symptoms two years before diagnosis.

In marked contrast to the originally reported 1- and 3-year mortality rates of 68% and 48%, respectively, recent registry data suggest that patients receiving combination PAH therapy have survival rates of 91% and 69% at 1 and 3 years, respectively.

Many patients now receive combination therapy with calcium channel blockers, phosphodiesterase type V inhibitors, endothelium type A and type B receptor antagonists, and prostaglandin I2 replacement therapies, with newer agents, including guanylyl cyclase stimulators and prostaglandin I2 receptor agonists, emerging in recent years.

For patients who require maximal medical therapy, referral for double lung transplant is recommended.

Prescription exercise, once regarded as potentially dangerous in PAH, has also become an important therapy in the management of the condition.

"Patients with PAH often require clinical care that is tailored to the individual patient," Dr. Maron said. "The medications used to treat these patients are diverse, expensive, and can be associated with important side effects, and must be used appropriately to increase the probability of a good outcome. Patients with PAH or who are at elevated risk for PAH should be managed by a pulmonary hypertension specialty care center."

"It is important for general medical doctors, cardiologists, and pulmonologists to consider the diagnosis of pulmonary arterial hypertension (PAH) in patients with shortness of breath, fatigue, dyspnea, decreased exercise tolerance or other symptoms that may seem non-specific," he said. "Earlier diagnosis is likely to hinge on higher awareness among the practicing community."

"Despite progress in the field of PAH, key questions remain unanswered that underpin disease expression and treatment," Dr. Maron added. "Opportunity exists to further our understanding of PAH basic mechanisms, clinical spectrum of risk, novel therapeutic targets, and optimal treatment strategies."

In a study reported in the same issue, Dr. Thenappan Thenappan from the University of Minnesota School of Medicine in Minneapolis and colleagues used data from the National Inpatient Sample database to examine recent trends and outcomes of PAH-related hospitalization in adults in the U.S.

Between 2001 and 2012, the number of PAH-related hospitalizations fell by 58%, from 3,177 to 1,345, at a time when there was no significant change in the total number of hospitalizations for all causes.

"The 58% decrease in number of admissions during the study period likely reflects an overall improvement in the outpatient care of these patients and likely favorable disease course with the availability of PAH-specific vasodilator therapies," the researchers note.

The average charge for those hospitalizations increased 2.7-fold, from $29,507 per hospitalization in 2001 to $79,607 per hospitalization in 2012.

In-hospital mortality of PAH patients did not change significantly between 2001 and 2012, and the average length of stay rose slightly from 7.0 days in 2001 to 7.6 days in 2012.

Factors independently associated with increased in-hospital mortality included admission to teaching hospitals, fluid and electrolyte imbalance, cardiac dysrhythmias, acute cerebrovascular accident, congestive heart failure, acute kidney injury, cardiogenic shock, and acute respiratory failure.

Admission to a teaching hospital, pneumonia, acute kidney injury, acute cerebrovascular accident, cardiac dysrhythmias, and acute respiratory failure were independent predictors of longer hospital stays.

"Taken together, these data highlight the increasing clinical and economic burden of PAH-related hospitalizations and should help identify patients with PAH who are at increased risk of prolonged hospitalization and in-hospital mortality," the authors conclude.

"The authors should be commended for their work identifying trends in hospitalization costs for PAH," write Dr. Stephen C. Mathai from Johns Hopkins University School of Medicine, Baltimore, Maryland and Dr. Vallerie V. McLaughlin from University of Michigan, Ann Arbor, in their invited commentary.

"However, their findings also highlight the significant gaps in knowledge that exist in our understanding of the characteristics, cost, and effect of hospitalizations on outcomes in PAH. We hope that further research clarifies these questions and leads to high-quality, cost-effective treatment of patients with this disease," they write.

Dr. Thenappan did not respond to a request for comments.

SOURCE:, and

JAMA Cardiol 2016.