Referral of patients with pulmonary hypertension diagnoses to tertiary pulmonary hypertension centers: the multicenter RePHerral study

JAMA Intern Med. 2013 May 27;173(10):887-93. doi: 10.1001/jamainternmed.2013.319.


Importance: Pulmonary hypertension (PH) is a fatal disease. Although the prognosis of pulmonary arterial hypertension (PAH) has improved with targeted therapies, the outcome is dependent on early detection and an accurate diagnosis.

Objective: To determine the accuracy of PH diagnoses in patients referred to PH centers and the frequency of PAH-specific medication use despite an uncertain or incorrect diagnosis.

Design: Multicenter, descriptive, cross-sectional study. During a 10-month period in 2010 and 2011, data on newly referred patients were collected and entered into a secure Internet database.

Setting: Three large tertiary PH centers.

Participants: One hundred forty consecutive patients newly referred to PH centers were invited to participate, and all consented to do so.

Results: Of 140 patients referred with a mean age of 56 years, 95 (68%) were referred by cardiologists or pulmonologists and 86 (61%) had disease classified as World Health Organization functional class III or IV. Fifty-six of the prereferral diagnoses (40%) were PAH, 42 (30%) unknown, and 22 (16%) PH secondary to lung disease or hypoxia. Of the 98 patients who received a definitive diagnosis before referral, 32 (33%) received a misdiagnosis. Fifty-nine patients underwent catheterization of the right and/or left side of the heart for the first time at the tertiary center. Of the 38 patients who underwent catheterization of the right side alone, 14 (37%) received a different diagnosis after undergoing the procedure; of the 21 patients who underwent catheterization of both sides of the heart, 11 (52%) received a different diagnosis after undergoing the procedures. Forty-two patients (30%) had started receiving PAH-specific medications before referral, with 24 of the prescriptions (57%) contrary to published guidelines.

Conclusions and relevance: Patients referred to PH centers for diagnosis and treatment are often referred late (with functional class III or IV disease), receive misdiagnoses, and are inappropriately prescribed medications. A reevaluation of educational efforts is required to improve awareness and the care and outcome of patients diagnosed as having PH.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Cross-Sectional Studies
  • Drug Prescriptions / statistics & numerical data*
  • Endothelin Receptor Antagonists*
  • Epoprostenol / analogs & derivatives*
  • Familial Primary Pulmonary Hypertension
  • Female
  • Humans
  • Hypertension, Pulmonary / diagnosis*
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Male
  • Middle Aged
  • Phosphodiesterase 5 Inhibitors / therapeutic use*
  • Referral and Consultation*
  • Retrospective Studies
  • United States


  • Antihypertensive Agents
  • Endothelin Receptor Antagonists
  • Phosphodiesterase 5 Inhibitors
  • Epoprostenol