Ian Stone publishes trial in AJRCCM

Congratulations to North East Thames trainee Dr Ian Stone who is first author of a paper in the blue journal, American Journal of Respiratory and Critical Care Medicine. He reports a double-blind, placebo-controlled, cross-over RCT investigating the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance.

As we know, COPD is associated with significant cardiovascular morbidity and mortality. A number of mechanisms through which this occurs have been suggested, including lung hyperinflation.  Associations between lung hyperinflation and cardiac structure and function exist, although it is unknown whether these changes are reversible with pharmacologic therapy. This study used cardiac MR to test the hypothesis that cardiac structural and functional alterations seen in stable hyperinflated COPD are modifiable through pharmacologic lung deflation.

Eligible patients were randomly assigned 1:1 to the two-period, complete-block crossover, receiving fluticasone furoate/vilanterol (FF/VI) 100/25 μg followed by placebo or placebo followed by FF/VI 100/25 μg once daily over two 7-day (maximum 14) treatment periods separated by a 7 ± 2–day washout period.

The primary outcome was change in right ventricular end-diastolic volume index (RVEDVI) from baseline versus placebo after 7 (maximum 14) days of treatment. Other pre-specified outcomes included cardiac structural, volumetric, and functional changes of the right ventricle (RV), left ventricle (LV), and left atrium compared with placebo; local and regional measures of aortic stiffness; pulmonary pulsatility; and lung function parameters.

Ian and co-authors conclude: “our study confirms that through pharmacologic treatment of COPD consistent and physiologically plausible beneficial effects on cardiac structure, function, and pulmonary vasculature can be achieved in the short term. Whether intrinsic myocardial function can be modulated through prolonged periods of lung deflation is as yet unverified and should be the focus of future clinical trials.”

As the accompanying editorial notes, this is a landmark study, with the changes to the RVEDV and LVEDV and RV and LV stroke volumes providing evidence of a “treatable underfilling” of the heart in hyperinflated patients with COPD. “This study leaves us with further questions. First, could cardiac function improve even more of two bronchodilators (a LABA and LAMA) are used? Second, considering the necessity of lifelong treatment in patients with COPD, how long can these effects be demonstrated? Third, what is the clinical relevance of these changes?”

Read the full text article here:

• Ian S. Stone, Neil C. Barnes, Wai-Yee James, Dawn Midwinter, Redha Boubertakh, Richard Follows, Leonette John, and Steffen E. Petersen. Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial. American Journal of Respiratory and Critical Care Medicine, Vol. 193, No. 7 (2016), pp. 717-726. doi: 10.1164/rccm.201508-1647OC

Read the accompanying editorial here:

• Henrik Watz. Chronic Obstructive Pulmonary Disease: When Pulmonologists Do Something Good for the Heart. American Journal of Respiratory and Critical Care Medicine, Vol. 193, No. 7 (2016), pp. 703-704. doi: 10.1164/rccm.201512-2340ED