title: Effect of indacaterol on lung deflation improves cardiac performance in hyperinflated COPD patients: an interventional, randomized, double-blind clinical trial.
abstract: BACKGROUND
  COPD is often associated with cardiovascular comorbidity. Treatment guidelines recommend therapy with bronchodilators as first choice. We investigated the acute effect of single-dose indacaterol on lung hyperinflation in COPD subjects, for the first time evaluating the potential effects on right heart performance.
  
  
  METHODS
  In this Phase IV, randomized, interventional, double-blind, crossover clinical study, we recruited 40 patients (50-85 years of age) with stable COPD. Patients were treated with 150 μg indacaterol or placebo and after 60 minutes (T60) and 180 minutes (T180) the following tests were performed: trans-thoracic echocardiography (TTE), plethysmography, diffusing capacity of the lung for carbon monoxide, saturation of peripheral oxygen, and visual analog scale dyspnea score. Patients underwent a crossover re-challenge after a further 72 hours of pharmacological washout. All TTE measurements were conducted blindly by the same operator and further interpreted by two different blinded operators. Consensus decisions were taken on every value and parameter. The primary outcome was the effect of the reduction of residual volume and functional residual capacity on right heart systolic and diastolic function indexes evaluated by TTE in patients treated with indacaterol, as compared to placebo.
  
  
  RESULTS
  Vital capacity, inspiratory capacity, and forced expiratory volume in 1 second were significantly increased by indacaterol, when compared with placebo, while residual volume, intrathoracic gas volume, and specific airway resistance were significantly reduced in patients treated with indacaterol. Tricuspid annular plane systolic excursion was significantly increased versus placebo, paralleled by an increase of tricuspid E-wave deceleration time. The cardiac frequency was also significantly reduced in indacaterol-treated patients.
  
  
  CONCLUSIONS
  Indacaterol significantly reduces lung hyperinflation in acute conditions, with a clinically relevant improvement of dyspnea. These modifications are associated with a significant increase of the right ventricular compliance indexes and may have a role in improving left ventricular preload leading to a reduction in cardiac frequency.
authors.affiliation: Department of Health Sciences, University of Milan, Milan, Italy ; Pulmonary Rehabilitation Unit, Fondazione Salvatore Maugeri Scientific Institute of Milan-IRCCS, University of Milan, Milan, Italy.
authors.forename: Pierachille
authors.initials: P
authors.lastname: Santus
authors.affiliation: Department of Health Sciences, University of Milan, Milan, Italy ; Pulmonary Rehabilitation Unit, Fondazione Salvatore Maugeri Scientific Institute of Milan-IRCCS, University of Milan, Milan, Italy.
authors.forename: Dejan
authors.initials: D
authors.lastname: Radovanovic
authors.affiliation: Cardiological Rehabilitation Unit, Fondazione Salvatore Maugeri Rehabilitation Institute of Milan-IRCCS, University of Milan, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Marco
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy ; Respiratory Unit, Policlinico San Donato-IRCCS, San Donato Milanese, Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valenti
authors.affiliation: Department of Health Sciences, University of Milan, Milan, Italy ; Pulmonary Rehabilitation Unit, Fondazione Salvatore Maugeri Scientific Institute of Milan-IRCCS, University of Milan, Milan, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Raccanelli
authors.affiliation: Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy ; IRCCS Fondazione Ospedale Maggiore Policlinico Cà Granda Milan, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.affiliation: Department of Health Sciences, University of Milan, Milan, Italy ; Respiratory Unit, Ospedale San Paolo, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Centanni
authors.affiliation: Cardiological Rehabilitation Unit, Fondazione Salvatore Maugeri Rehabilitation Institute of Milan-IRCCS, University of Milan, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bussotti
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage; D000368:Aged; D000369:Aged, 80 and over; D000403:Airway Resistance / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy*; D004452:Echocardiography; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D007320:Inspiratory Capacity / Q000187:drug effects; D008176:Lung Volume Measurements; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D015363:Quinolones / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D007189:Indans; D015363:Quinolones; C510790:indacaterol
keywords: bronchodilator; cardiac performance; echocardiography; lung deflation; right ventricular function