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Original Research: Pulmonary Vascular Disease |

Elevation of Plasma Cell-Free Hemoglobin in Pulmonary Arterial HypertensionCell-Free Hemoglobin in PAH

Evan L. Brittain, MD, MSCI; David R. Janz, MD, MSCI; Eric D. Austin, MD, MSCI; Julie A. Bastarache, MD; Lisa A. Wheeler, BS; Lorraine B. Ware, MD; Anna R. Hemnes, MD
Author and Funding Information

From the Division of Cardiovascular Medicine (Dr Brittain), the Division of Allergy, Pulmonary and Critical Care Medicine (Drs Janz, Bastarache, Ware, and Hemnes and Ms Wheeler), and the Department of Pediatrics (Dr Austin), Vanderbilt University Medical School, Nashville, TN.

CORRESPONDENCE TO: Evan L. Brittain, MD, MSCI, Division of Cardiovascular Medicine, Vanderbilt University Medical School, 2525 W End Ave, Ste 300, Nashville, TN 37203; e-mail: evan.brittain@vanderbilt.edu


FUNDING/SUPPORT: This work was supported by the American Heart Association Fellow to Faculty Award and American College of Cardiology Foundation/Merck Fellowship (Dr Brittain), the American Heart Association Established Investigator Award (Dr Ware), the National Institutes of Health [Grants T32 HL087738 (Dr Janz), K08 HL093363 (Dr Hemnes), K23 HL0987431 (Dr Austin), R21 HL117676 (Dr Bastarache), and K24 HL103836 (Dr Ware)], and National Center for Research Resources/National Institutes of Health [Grant 1 UL1 RR024975 (Vanderbilt)].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(6):1478-1485. doi:10.1378/chest.14-0809
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BACKGROUND:  Cell-free hemoglobin (CFH) is a potent nitric oxide scavenger associated with poor outcomes in several diseases. Pulmonary arterial hypertension (PAH) is characterized by reduced nitric oxide availability. We hypothesized that CFH would be elevated in PAH and would associate with hemodynamics and clinical outcomes.

METHODS:  We measured CFH in 200 consecutively evaluated patients with PAH, 16 unaffected bone morphogenetic receptor protein type 2 (BMPR2) mutation carriers, 19 healthy subjects, and 29 patients with pulmonary venous hypertension (PVH). CFH values were tested for association with hemodynamics, time to hospitalization, and death.

RESULTS:  CFH was elevated in patients with PAH and BMPR2 carriers compared with healthy subjects and patients with PVH (P ≤ .01 all comparisons). There were no differences in CFH across PAH subtypes. CFH modestly correlated with mean pulmonary artery pressure (ρ = 0.16, P = .03) and pulmonary vascular resistance (ρ = 0.21, P = .01) and inversely with cardiac index (ρ = −0.18, P = .02) in patients with PAH. CFH was not associated with hemodynamic response to nitric oxide or death. Patients with the highest CFH levels had increased risk of PAH-related hospitalization when adjusted for age, sex, and PAH cause (hazard ratio, 1.69; 95% CI ,1.08-2.66; P = .02).

CONCLUSIONS:  CFH is elevated in patients with PAH and BMPR2 carriers compared with healthy subjects and patients with PVH. Elevated CFH levels are independently associated with an increased risk of hospitalization. Further study is required to understand the mechanism of CFH elevation and the potential pathologic contribution of CFH in PAH.

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