Lung Deflation and Cardiovascular Structure and Function in COPD: A Randomized Controlled Trial.

Abstract

RATIONALE: Chronic obstructive pulmonary disease patients develop increased cardiovascular morbidity with structural alterations. OBJECTIVES: This double-blind, placebo-controlled, crossover study investigated the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. METHODS: Forty-five hyperinflated chronic obstructive pulmonary disease patients were randomised (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: change from baseline in right ventricular end diastolic volume index versus placebo. MEASUREMENTS AND MAIN RESULTS: There was a 5.8 ml/m2 (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/m2 (P = 0.002) and 2.33 ml/m2 (P = 0.002). In post-hoc analysis, right ventricular stroke volume increased by 4.87 ml/m2 (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: Pharmacological 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 registration available at www.clinicaltrials.gov, ID NCT01691885.