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

Abstract

Rationale: Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations.

Objectives: 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.

Measurements and main 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).

Trial registration: ClinicalTrials.gov NCT01691885.

Keywords: cardiac function; cardiac magnetic resonance; chronic obstructive pulmonary disease; fluticasone furoate/vilanterol; lung hyperinflation.

Figure 1.

Study design and enrollment and outcomes. (A) Design of the study. Each patient, in two separate treatment periods, received 7 (maximum 14) days of treatment and matching placebo separated by a 1-week washout period. (B) Screening, randomization, treatment, and follow-up of patients. *One patient withdrew from the analysis owing to missing MRI data. AE = adverse event; CMR = cardiac magnetic resonance; COPD = chronic obstructive pulmonary disease; FF/VI = fluticasone furoate/vilanterol; LRTI = lower respiratory tract infection; MRI = magnetic resonance imaging; QD = once daily.

Figure 2.

Primary cardiovascular efficacy outcomes. Box plot of change from baseline in right ventricular end-diastolic volume index (RVEDVI) for fluticasone furoate/vilanterol (FF/VI) 100/25 μg once daily versus placebo after 7–14 days of treatment. Baseline is the assessment taken at predose on Day 1.

Figure 3.

Forest plot of change from baseline in the other cardiovascular efficacy outcomes for fluticasone furoate/vilanterol (FF/VI) 100/25 μg once daily versus placebo after 7–14 days of treatment. Baseline is the assessment taken at predose on Day 1. Analysis was performed using an analysis of covariance model with covariates of treatment, baseline, period, and subject as a random effect. Data presented represent (change from baseline during FF/VI period – change from baseline in placebo period) with 95% CIs. ABA = abdominal aorta; CI = confidence interval; EDVI = end-diastolic volume index; EF = ejection fraction; ESVI = end-systolic volume index; LPA = left pulmonary artery; MI = mass index; MPA = main pulmonary artery; RPA = right pulmonary artery; SVI = stroke volume index; TAA = thoracic ascending aorta; TDA = thoracic descending aorta.