Arterial Vascular Pruning, Right Ventricular Size, and Clinical Outcomes in Chronic Obstructive Pulmonary Disease. A Longitudinal Observational Study

Abstract

Rationale: Cor pulmonale (right ventricular [RV] dilation) and cor pulmonale parvus (RV shrinkage) are both described in chronic obstructive pulmonary disease (COPD). The identification of emphysema as a shared risk factor suggests that additional disease characterization is needed to understand these widely divergent cardiac processes.Objectives: To explore the relationship between computed tomography measures of emphysema and distal pulmonary arterial morphology with RV volume, and their association with exercise capacity and mortality in ever-smokers with COPD enrolled in the COPDGene Study.Methods: Epicardial (myocardium and chamber) RV volume (RV_EV), distal pulmonary arterial blood vessel volume (arterial BV5: vessels <5 mm² in cross-section), and objective measures of emphysema were extracted from 3,506 COPDGene computed tomography scans. Multivariable linear and Cox regression models and the log-rank test were used to explore the association between emphysema, arterial BV5, and RV_EV with exercise capacity (6-min-walk distance) and all-cause mortality.Measurements and Main Results: The RV_EV was approximately 10% smaller in Global Initiative for Chronic Obstructive Lung Disease stage 4 versus stage 1 COPD (P < 0.0001). In multivariable modeling, a 10-ml decrease in arterial BV5 (pruning) was associated with a 1-ml increase in RV_EV. For a given amount of emphysema, relative preservation of the arterial BV5 was associated with a smaller RV_EV. An increased RV_EV was associated with reduced 6-minute-walk distance and in those with arterial pruning an increased mortality.Conclusions: Pulmonary arterial pruning is associated with clinically significant increases in RV volume in smokers with COPD and is related to exercise capacity and mortality in COPD.Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

Keywords: COPD; computed tomography; right ventricle; vascular pruning.

Figure 1.

Pulmonary vasculature and right (blue) and left (red) ventricular reconstructions from computed tomography images for two subjects with approximately 20% emphysema on computed tomography scan. (A, C, and E) Subject 1 with 19% emphysema and relative preservation of the distal arterial vascular volume (arterial volume for vessels less than 5 mm² in cross-section = 131 ml). (B, D, and F) Subject 2 with 18% emphysema and relative loss of the distal arterial vascular volume (arterial volume for vessels less than 5 mm² in cross-section = 70.8 ml). (A and B) Axial images of the epicardial surface of the right ventricle (RV), which is outlined in blue and the epicardial surface of the left ventricle, which is outlined in red. Emphysema is depicted in green. (C and D) Frontal view of the arterial (blue) and venous vasculature and the surface model of the epicardial (myocardium and chamber) RV volume (blue) and epicardial (myocardium and chamber) left ventricular volume (red). The epicardial (myocardium and chamber) RV volume of Subject 1 is 58.9 ml and the epicardial (myocardium and chamber) RV volume for Subject 2 is 140 ml. (E and F) Sagittal views of the arterial (blue) and venous (red) vasculature of the left lung demonstrating the relative loss of distal arterial vascular volume. Emphysema is shown in green.

Figure 2.

Median (and interquartile range) epicardial (myocardium and chamber) right ventricular volume by sex (top two panels) or race (bottom two panels) and Global Initiative for Chronic Obstructive Lung Disease stage. GOLD = Global Initiative for Chronic Obstructive Lung Disease; RV = right ventricular.

Figure 3.

(Top left) Survival in those participants with right ventricular (RV) enlargement with and without arterial pruning. (Top right) Survival by RV size in those without arterial pruning. (Bottom left) Survival by the presence or absence of arterial pruning in those without enlarged RVs. (Bottom right) Survival in small versus large RV size in those with arterial pruning. An enlarged right ventricle (epicardial [myocardium and chamber] RV volume) is defined as those in the highest quartile of RV volume compared with those in the bottom three quartiles. Pruning is defined as those with an arterial volume for vessels less than 5 mm² in cross-section less than the median.