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

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 ß2-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).

Reproducibility of arterial stiffness and wave reflections in chronic obstructive pulmonary disease: the contribution of lung hyperinflation and a comparison of techniques.

Significant cardiovascular morbidity and mortality exists in chronic obstructive pulmonary disease (COPD). Arterial stiffness is raised in COPD and may be a mechanistic link. Non-invasive assessment of arterial stiffness has the potential to be a surrogate outcome measure, although no reproducibility data exists in COPD patients. Two studies (23 and 33 COPD patients) were undertaken to 1) assess the Vicorder reproducibility of carotid-femoral pulse wave velocity and Augmentation index in COPD; 2) compare it to SphygmoCor; and 3) assess the contribution of lung hyperinflation to measurement variability. There were excellent correlations and good agreement between repeat Vicorder measurements for carotid-femoral pulse wave velocity (r = 0.96 (p < 0.001); mean difference ±SD = -0.03 ± 0.36 m/s (p = 0.65); co-efficient of reproducibility = 4.02%; limits of agreement = -0.68-0.75 m/s). Augmentation index significantly correlated (r = 0.736 (p < 0.001); mean difference ±SD = 0.72 ± 4.86% (p = 0.48), however limits of agreement were only 10.42-9.02%, with co-efficient of reproducibility of 27.93%. Comparing devices, Vicorder values were lower but there was satisfactory agreement. There were no correlation between lung hyperinflation (as measured by residual volume percent predicted, total lung capacity percent predicted or the ratio of inspiratory capacity to residual volume) and variability of measurements in either study. In COPD, measurement of carotid-femoral pulse wave velocity is highly reproducible, not affected by lung hyperinflation and suitable as a surrogate endpoint in research studies. Day-to-day variation in augmentation index highlights the importance of such studies prior to the planning and undertaking of clinical COPD research.