Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial

• Published in: American journal of respiratory and critical care medicine Vol. 193; no. 7; pp. 717 - 726
• Main Authors: Stone, Ian S, Barnes, Neil C, James, Wai-Yee, Midwinter, Dawn, Boubertakh, Redha, Follows, Richard, John, Leonette, Petersen, Steffen E
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.04.2016
• Subjects: Administration, Inhalation; Adrenal Cortex Hormones - administration & dosage; Adrenergic beta-2 Receptor Agonists - administration & dosage; Aged; Androstadienes - administration & dosage; Benzyl Alcohols - administration & dosage; Bronchodilator Agents - administration & dosage; Chlorobenzenes - administration & dosage; Cross-Over Studies; Drug Combinations; Female; Forced Expiratory Volume - drug effects; Heart - drug effects; Heart - physiopathology; Humans; Lung - drug effects; Lung - pathology; Lung - physiopathology; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium - pathology; Original; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; fluticasone furoate/vilanterol; lung hyperinflation; cardiac function; cardiac magnetic resonance; chronic obstructive pulmonary disease
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201508-1647OC

Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. 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. 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. 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).