title: Increased myocardial extracellular volume in active idiopathic systemic capillary leak syndrome.
abstract: BACKGROUND
  The Systemic Capillary Leak Syndrome (SCLS) is a rare disorder of unknown etiology presenting as recurrent episodes of shock and peripheral edema due to leakage of fluid into soft tissues. Insights into SCLS pathogenesis are few due to the scarcity of cases, and the etiology of vascular barrier disruption in SCLS is unknown. Recent advances in cardiovascular magnetic resonance (CMR) allow for the quantitative assessment of the myocardial extracellular volume (ECV), which can be increased in conditions causing myocardial edema. We hypothesized that measurement of myocardial ECV may detect myocardial vascular leak in patients with SCLS.
  
  
  METHODS
  Fifty-six subjects underwent a standard CMR examination at the NIH Clinical Center from 2009 until 2014: 20 patients with acute intermittent SCLS, six subjects with chronic SCLS, and 30 unaffected controls. Standard volumetric measurements; late gadolinium enhancement imaging and pre- and post-contrast T1 mapping were performed. ECV was calculated by calibration of pre- and post-contrast T1 values with blood hematocrit.
  
  
  RESULTS
  Demographics and cardiac parameters were similar in both groups. There was no significant valvular disorder in either group. Subjects with chronic SCLS had higher pre-contrast myocardial T1 compared to healthy controls (T1: 1027 ± 44 v. 971 ± 41, respectively; p = 0.03) and higher myocardial ECV than patients with acute intermittent SCLS or controls: 33.8 ± 4.6, 26.9 ± 2.6, 26 ± 2.4, respectively; p = 0.007 v. acute intermittent; P = 0.0005 v. controls). When patients with chronic disease were analyzed together with five patients with acute intermittent disease who had just experienced an acute SCLS flare, ECV values were significantly higher than in subjects with acute intermittent SCLS in remission or age-matched controls and (31.2 ± 4.6 %, 26.5 ± 2.7 %, 26 ± 2.4 %, respectively; p = 0.01 v. remission, p = 0.001 v. controls). By contrast, T1 values did not distinguish these three subgroups (1008 ± 40, 978 ± 40, 971 ± 41, respectively, p = 0.2, active v. remission; p = 0.06 active v. controls). Abundant myocardial edema without evidence of acute inflammation was detected in cardiac tissue postmortem in one patient.
  
  
  CONCLUSIONS
  Patients with active SCLS have significantly higher myocardial ECV than age-matched controls or SCLS patients in remission, which correlated with histopathological findings in one patient.
authors: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.|Medstar Washington Hospital Center, Washington, DC, USA.
authors: Andrew
authors: A
authors: Ertel
authors: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Drew
authors: D
authors: Pratt
authors: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Peter
authors: P
authors: Kellman
authors: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.|University of Kentucky, Lexington, KY, USA.
authors: Steve
authors: S
authors: Leung
authors: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Patricia
authors: P
authors: Bandettini
authors: National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive Room 4154, Bethesda, MD, 20892-8305, USA.
authors: Lauren M
authors: LM
authors: Long
authors: National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive Room 4154, Bethesda, MD, 20892-8305, USA.
authors: Michael
authors: M
authors: Young
authors: National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive Room 4154, Bethesda, MD, 20892-8305, USA.
authors: Celeste
authors: C
authors: Nelson
authors: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Andrew E
authors: AE
authors: Arai
authors: National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive Room 4154, Bethesda, MD, 20892-8305, USA. kdruey@niaid.nih.gov.
authors: Kirk M
authors: KM
authors: Druey
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D001706:Biopsy; D019559:Capillary Leak Syndrome / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability; D016022:Case-Control Studies; D002908:Chronic Disease; D004489:Edema, Cardiac / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008396:Maryland; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D009316:National Institutes of Health (U.S.); D011237:Predictive Value of Tests; D011379:Prognosis; D013318:Stroke Volume; D014481:United States; D016277:Ventricular Function, Left