Pulmonary Artery Relative Area Change Detects Mild Elevations in Pulmonary Vascular Resistance and Predicts Adverse Outcome in Pulmonary Hypertension Andrew J. Swift, FRCR,*Þ Smitha Rajaram, FRCR,* Robin Condliffe, MD,Þþ Dave Capener, BSc,* Judith Hurdman, MRCP,þ Charlie Elliot, MRCP,Þþ David G. Kiely, MD,Þþ and Jim M. Wild, PhD*Þ Objective: The aim of this study was to evaluate the clinical use of magnetic resonance imaging measurements related to pulmonary artery stiffness in the evaluation of pulmonary hypertension (PH). Materials and Methods: A total of 134 patients with suspected PH underwent right heart catheterization (RHC) and magnetic resonance imaging on a 1.5-T scanner within 2 days. Phase contrast imaging at the pulmonary artery trunk and cine cardiac views were acquired. Pulmonary artery area change (AC), relative AC (RAC), compliance (AC/pulse pressure from RHC), distensibility (RAC/pulse pressure from RHC), right ventricular functional indices, and right ventricular mass were all derived. Regression curve fitting identified the statistical model of best fit between RHC measurements and pulmonary artery stiffness indices. The diagnostic accuracy and prognostic value of noninvasive AC and RAC were also assessed. Results: The relationship between pulmonary vascular resistance and pul- monary artery RAC was best reflected by an inverse linear model. Patients with mild elevation in pulmonary vascular resistance (G4 Woods units) demonstrated reduced RAC (P = 0.02) and increased right ventricular mass index (P G 0.0001) without significant loss of right ventricular function (P = 0.17). At follow-up of 0 to 40 months, 18 patients with PH had died (16%). Analysis of Kaplan-Meier plots showed that both AC and RAC pre- dicted mortality (log-rank test, P = 0.046 and P = 0.012, respectively). Area change and RAC were also predictors of mortality using univariate Cox pro- portional hazards regression analysis (P = 0.046 and P = 0.03, respectively). Conclusions: Noninvasive assessment of pulmonary artery RAC is a marker sensitive to early increased vascular resistance in PH and is a predictor of adverse outcome. Key Words: MRI, pulmonary hypertension, pulmonary vascular resistance, pulmonary artery stiffness, prognosis (Invest Radiol 2012;47: 571Y577) P ulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (mPAP) greater than or equal to 25 mm Hg measured at cardiac catheterization. With the growing availability of effective therapy, 1 early detection of mild elevations in pulmonary vascular resistance (PVR) is of great importance. 2 Imaging plays an important role for the noninvasive screening of patients with suspected PH; however, few studies have evaluated quantitative noninvasive tests in patients with mild elevations in PVR. Noninvasive estimation of PVR is also highly desirable because it has diagnostic and prognostic value in PH. The pulmonary arterial tree and right ventricle act as a unit. Pulsatile blood flow is generated from right ventricular (RV) con- traction driving blood through the pulmonary arteries toward the capillary bed. In patients with PH, increased vascular resistance is thought to cause increased vascular stiffness, 3,4 reduced blood flow velocity, 5Y7 and dilatation of the pulmonary arteries 8 ; this impacts on the RV-pulmonary artery unit, with increased RV workload even- tually resulting in RV remodelling with dilatation and hypertrophy. 9Y13 Pulmonary artery stiffness has been assessed in previous studies of patients with PH. 3,4,14Y18 Sanz et al 3 evaluated unselected patients with PH at rest and patients with exercise-induced PH; they dem- onstrated a strong relationship between measures of pulmonary ar- tery stiffness and PH severity and found alterations in pulmonary arterial stiffness parameters derived from magnetic resonance im- aging (MRI) in patients with exercise-induced PH, indicating po- tential sensitivity for the identification of early PH. Studies evaluating the prognostic value of pulmonary arterial stiffness in patients with pulmonary arterial hypertension (PAH) have shown that reduced capacitance measured at right heart catheterization (RHC) predicts mortality in idiopathic PAH (IPAH), 17,19,20 and MRI determined pulmonary arterial relative area change (RAC) also predicts mor- tality in PAH. However, these studies have not investigated the re- lationship between pulmonary artery stiffness and PVR or explored why increased vascular stiffness is a potential marker of early pul- monary vascular disease. The aim of this study was to evaluate whether the noninvasive assessment of pulmonary arterial stiffness measurements can identify patients with PH who have mild elevation of PVR and determine the prognostic significance of noninvasive pulmonary arterial stiff- ness in an unselected cohort of consecutive patients with PH. MATERIALS AND METHODS Patients We retrospectively studied 134 consecutive patients with sus- pected PH who underwent RHC and cardiac MRI within a 2-day period. Patients were referred with suspected PH with symptoms or imaging findings suggestive of the diagnosis of PH. Our PH patient group included 21 patients with IPAH, 20 patients with PAH asso- ciated with connective tissue disease, 2 patients with PAH associated with portal hypertension, 3 patients with PAH associated with con- genital heart disease, 14 patients with PH owing to left heart disease, 14 patients with PH due to lung diseases and/or hypoxia (PH-RESP), and 41 patients with chronic thromboembolic PH (CTEPH). 21 The 19 patients found to have an mPAP less than 25 mm Hg at RHC served as controls. Patients with PH were divided into 2 groups based on the severity of PVR: patients in group A (n = 37) had PVR less than 4 Woods units (WU) and patients in group B (n = 78) had ORIGINAL ARTICLE Investigative Radiology & Volume 47, Number 10, October 2012 www.investigativeradiology.com 571 Received for publication December 5, 2011; and accepted for publication, after revision, May 20, 2012. From the *Unit of Academic Radiology, University of Sheffield; †National Insti- tutes of Health Research, Cardiovascular Biomedical Research Unit; and ‡Sheffield Pulmonary Vascular Clinic, Sheffield Teaching Hospitals Trust, Sheffield, UK. Conflicts of interest and sources offunding: A.J.S., R.C., C.E., J.M.W., and D.G.K. receive funding from the National Institute for Health Research via its Bio- medical Research Units funding scheme. J.M.W. is also funded by the Engi- neering and Physical Sciences Research Council. D.C. receives funding from Bayer Schering; S.R., from Pfizer; and J.H., from Actelion Pharmaceuticals. The authors report no conflicts of interest. Reprints: Andrew J. Swift, FRCR, University of Sheffield, Academic Unit of Ra- diology, C Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2J, UK. E-mail: a.j.swift@shef.ac.uk. Copyright * 2012 by Lippincott Williams & Wilkins ISSN: 0020-9996/12/4710Y0571 Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.