title: Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.
abstract: BACKGROUND
  Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations.
  
  
  OBJECTIVE
  To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance.
  
  
  METHODS
  Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting β2-agonist fluticasone furoate/vilanterol 100/25 μg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo.
  
  
  RESULTS
  There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P < 0.001) increase in change from baseline right ventricular end-diastolic volume index and a 429 ml (P < 0.001) reduction in residual volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P < 0.001). Intrinsic myocardial function was unchanged. Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo.
  
  
  CONCLUSIONS
  Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).
authors.affiliation: 1 Department of Respiratory Medicine, The London Chest Hospital, Barts Health NHS Trust, London, United Kingdom.|2 William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; and.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Stone
authors.affiliation: 2 William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; and.|3 Global Respiratory Department, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Barnes
authors.affiliation: 1 Department of Respiratory Medicine, The London Chest Hospital, Barts Health NHS Trust, London, United Kingdom.
authors.forename: Wai-Yee
authors.initials: WY
authors.lastname: James
authors.affiliation: 3 Global Respiratory Department, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom.
authors.forename: Dawn
authors.initials: D
authors.lastname: Midwinter
authors.affiliation: 2 William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; and.
authors.forename: Redha
authors.initials: R
authors.lastname: Boubertakh
authors.affiliation: 3 Global Respiratory Department, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Follows
authors.affiliation: 1 Department of Respiratory Medicine, The London Chest Hospital, Barts Health NHS Trust, London, United Kingdom.
authors.forename: Leonette
authors.initials: L
authors.lastname: John
authors.affiliation: 2 William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; and.
authors.forename: Steffen E
authors.initials: SE
authors.lastname: Petersen
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage*; D001592:Benzyl Alcohols / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage; D002722:Chlorobenzenes / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; D004338:Drug Combinations; C550468:vilanterol; C523187:fluticasone furoate
keywords: cardiac function; cardiac magnetic resonance; chronic obstructive pulmonary disease; fluticasone furoate/vilanterol; lung hyperinflation