Mechanisms Underlying the Association of Chronic Obstructive Pulmonary Disease With Heart Failure

Abstract

Objectives: The purposes of this study were to determine why chronic obstructive pulmonary disease (COPD) is associated with heart failure (HF). Specific objectives included whether COPD is associated with myocardial fibrosis, whether myocardial fibrosis is associated with hospitalization for HF and death in COPD, and whether COPD and smoking are associated with myocardial inflammation.

Background: COPD is associated with HF independent of shared risk factors. The underlying pathophysiological mechanism is unknown.

Methods: A prospective, multicenter, longitudinal cohort study of 572 patients undergoing cardiac magnetic resonance (CMR), including 450 patients with COPD and 122 age- and sex-matched patients with a median: 726 days (interquartile range: 492 to 1,160 days) follow-up. Multivariate analysis was used to examine the relationship between COPD and myocardial fibrosis, measured using cardiac magnetic resonance (CMR). Cox regression analysis was used to examine the relationship between myocardial fibrosis and outcomes; the primary endpoint was composite of hospitalizations for HF or all-cause mortality; secondary endpoints included hospitalizations for HF and all-cause mortality. Fifteen patients with COPD, 15 current smokers, and 15 healthy volunteers underwent evaluation for myocardial inflammation, including ultrasmall superparamagnetic particles of iron oxide CMR.

Results: COPD was independently associated with myocardial fibrosis (p < 0.001). Myocardial fibrosis was independently associated with the primary outcome (hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.08 to 1.20; p < 0.001), hospitalization for HF (HR: 1.25 [95% CI: 1.14 to 1.36]); p < 0.001), and all-cause mortality. Myocardial fibrosis was associated with outcome measurements more strongly than any other variable. Acute and stable COPD were associated with myocardial inflammation.

Conclusions: The associations between COPD, myocardial inflammation and myocardial fibrosis, and the independent prognostic value of myocardial fibrosis elucidate a potential pathophysiological link between COPD and HF.

Keywords: cardiac magnetic resonance; chronic obstructive pulmonary disease; heart failure; mortality; myocardial fibrosis; myocardial inflammation.

Graphical abstract

Central Illustration

Myocardial Fibrosis and Survival Free From Hospitalization for Heart Failure or All-Cause Mortality Kaplan-Meier curve for survival free from a composite of all-cause mortality or hospitalization for heart failure (HHF) in patients with chronic obstructive pulmonary disease, according to myocardial fibrosis burden. Myocardial fibrosis was measured using cardiac magnetic resonance extracellular volume (ECV). MRI = magnetic resonance imaging.

Figure 1

Myocardial Fibrosis and Survival Free From Hospitalization for Heart Failure Kaplan-Meier curve for survival free from hospitalization for heart failure in patients with chronic obstructive pulmonary disease, according to myocardial fibrosis burden. Myocardial fibrosis was measured using cardiac magnetic resonance extracellular volume (ECV). MRI = magnetic resonance imaging.

Figure 2

USPIO-Enhanced CMR Measurements in Patients With COPD During Acute Exacerbation (Acute COPD) and When Stable (Stable COPD), Current Smokers, and Healthy Volunteers (A) Myocardial R2∗. (B) Myocardial R2∗/R1 ratio. Scan 1 = baseline CMR scan before USPIO administration. Scans 2 and scan 3 = CMR scans performed at 48 and 72 hours, respectively, following USPIO administration. CMR = cardiac magnetic resonance; COPD = chronic obstructive pulmonary disease; USPIO = ultrasmall superparamagnetic particles of iron oxide.