Roham T Zamanian1,2, Haley Hedlin3, Paul Greuenwald4, David M Wilson5, Joshua I Segal6, Michelle Jorden7, Kristina Kudelko1,2, Juliana Liu1,2, Andrew Hsi1,2, Allyson Rupp1,2, Andrew J Sweatt1,2, Rubin Tuder8, Gerald J Berry6, Marlene Rabinovitch2,9, Ramona L Doyle10, Vinicio de Jesus Perez1,2, Steven M Kawut11. 1. 1 Division of Pulmonary and Critical Care Medicine. 2. 2 Vera Moulton Wall Center for Pulmonary Vascular Disease at Stanford, and. 3. 3 Quantitative Sciences Unit, Stanford University School of Medicine, Stanford, California. 4. 4 Pacific Institute for Research and Evaluation, Oakland, California. 5. 5 Swedish Medical Center, Seattle, Washington. 6. 6 Department of Pathology, Stanford University School of Medicine, Stanford, California. 7. 7 Santa Clara County Medical Examiner, Santa Clara, California. 8. 8 Pulmonary Sciences and Critical Care Medicine, University of Colorado, Denver, Colorado. 9. 9 Department of Pediatrics, Stanford University School of Medicine, Stanford, California. 10. 10 University of California San Francisco, San Francisco, California; and. 11. 11 Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract
RATIONALE: Although amphetamines are recognized as "likely" agents to cause drug- and toxin-associated pulmonary arterial hypertension (PAH), (meth)amphetamine-associated PAH (Meth-APAH) has not been well described. OBJECTIVES: To prospectively characterize the clinical presentation, histopathology, and outcomes of Meth-APAH compared with those of idiopathic PAH (iPAH). METHODS: We performed a prospective cohort study of patients with Meth-APAH and iPAH presenting to the Stanford University Pulmonary Hypertension Program between 2003 and 2015. Clinical, pulmonary angiography, histopathology, and outcomes data were compared. We used data from the Healthcare Cost and Utilization Project to estimate the epidemiology of PAH in (meth)amphetamine users hospitalized in California. MEASUREMENTS AND MAIN RESULTS: The study sample included 90 patients with Meth-APAH and 97 patients with iPAH. Patients with Meth-APAH were less likely to be female, but similar in age, body mass index, and 6-minute-walk distance to patients with iPAH. Patients with Meth-APAH reported more advanced heart failure symptoms, had significantly higher right atrial pressure (12.7 ± 6.8 vs. 9.8 ± 5.1 mm Hg; P = 0.001), and had lower stroke volume index (22.2 ± 7.1 vs. 25.5 ± 8.7 ml/m2; P = 0.01). Event-free survival in Meth-APAH was 64.2%, 47.2%, and 25% at 2.5, 5, and 10 years, respectively, representing more than double the risk of clinical worsening or death compared with iPAH (hazard ratio, 2.04; 95% confidence interval, 1.28-3.25; P = 0.003) independent of confounders. California data demonstrated a 2.6-fold increase in risk of PAH diagnosis in hospitalized (meth)amphetamine users. CONCLUSIONS: Meth-APAH is a severe and progressive form of PAH with poor outcomes. Future studies should focus on mechanisms of disease and potential therapeutic considerations.
RATIONALE: Although amphetamines are recognized as "likely" agents to cause drug- and toxin-associated pulmonary arterial hypertension (PAH), (meth)amphetamine-associated PAH (Meth-APAH) has not been well described. OBJECTIVES: To prospectively characterize the clinical presentation, histopathology, and outcomes of Meth-APAH compared with those of idiopathic PAH (iPAH). METHODS: We performed a prospective cohort study of patients with Meth-APAH and iPAH presenting to the Stanford University Pulmonary Hypertension Program between 2003 and 2015. Clinical, pulmonary angiography, histopathology, and outcomes data were compared. We used data from the Healthcare Cost and Utilization Project to estimate the epidemiology of PAH in (meth)amphetamine users hospitalized in California. MEASUREMENTS AND MAIN RESULTS: The study sample included 90 patients with Meth-APAH and 97 patients with iPAH. Patients with Meth-APAH were less likely to be female, but similar in age, body mass index, and 6-minute-walk distance to patients with iPAH. Patients with Meth-APAH reported more advanced heart failure symptoms, had significantly higher right atrial pressure (12.7 ± 6.8 vs. 9.8 ± 5.1 mm Hg; P = 0.001), and had lower stroke volume index (22.2 ± 7.1 vs. 25.5 ± 8.7 ml/m2; P = 0.01). Event-free survival in Meth-APAH was 64.2%, 47.2%, and 25% at 2.5, 5, and 10 years, respectively, representing more than double the risk of clinical worsening or death compared with iPAH (hazard ratio, 2.04; 95% confidence interval, 1.28-3.25; P = 0.003) independent of confounders. California data demonstrated a 2.6-fold increase in risk of PAH diagnosis in hospitalized (meth)amphetamine users. CONCLUSIONS:Meth-APAH is a severe and progressive form of PAH with poor outcomes. Future studies should focus on mechanisms of disease and potential therapeutic considerations.
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