The impact of pulmonary fibrosis on cardiac function in chronic obstructive pulmonary disease
Authors: Stolen K , Duus L S , Vesterlev D , Janner E H , Arendschneider O , Karsum E , Sivapalan P , Ulrik C S , Lapperre T , Browatzki A , Estepar R S J , Nardelli P , Jensen J U S , Estepar R S J , Biering-Sorensen T 
Published: October 2024

Abstract

Background
Emerging evidence indicates the coexistence pulmonary fibrosis and emphysema in patients with Chronic Obstructive Pulmonary Disease (COPD). The effect of pulmonary fibrosis on cardiac structure and function in COPD patients remains unclear.

Purpose
This study aimed to examine the association between the degree of pulmonary fibrosis identified on Computed Tomographic (CT) imaging and echocardiographic measures of cardiac structure and function in individuals with COPD.

Methods
The study included 456 individuals with COPD, participating in a large prospective cohort study. Patients with available CT scans and echocardiograms were included. Local histogram-based assessments of lung density were utilized to determine the percentage of fibrosis. Fibrosis was defined based on the CT attenuation within the range of -600 and -250 Hounsfield units. The association between percent fibrosis and measures of cardiac structure and function were investigated by univariable and multivariable linear regression models. Multivariable adjustments included age, sex, body mass index (BMI), and smoking. In addition, restricted cubic splines were generated to visually present the relationship between the percentage of fibrosis and specific echocardiographic parameters.

Results
The mean age was 71 (± 8 years), 48% were female, and the median BMI was 27 kg/m2 (IQR: 22; 30kg/m2). The mean forced expiratory volume in 1 second as a percentage of the predicted value (FEV1pp) was 47% (±18%). The mean forced vital capacity of predicted value was 71% (± 19%). The median percentage of fibrosis in the cohort was 4.9% (IQR: 3.9; 6.0%). Patients were stratified into tertiles based upon fibrosis percentage. BMI, frequency of diabetes, and FEV1pp were increasingly positively associated with fibrosis. Furthermore, significant trends for echocardiographic measures found that the patients with the most extensive fibrosis were seen to have impaired left ventricular (LV) ejection fraction (LVEF), lower absolute global longitudinal strain (GLS), increased left atrial (LA) volume index (LAVi), and higher LV mass as compared to those with less significant fibrosis. There were no significant differences between tertiles of fibrosis and age or sex. In univariable linear regression, significant inverse associations between the percentage of fibrosis, LVEF, GLS, and tricuspid annular plane systolic excursion (TAPSE) were seen (Table). For LV mass index and LAVi, significant direct associations were found (Table). After adjusting for potential confounding factors, only GLS and LAVi remained associated with pulmonary fibrosis (Figure).

Conclusion
This study found that GLS and LA volume were significantly associated with the degree of pulmonary fibrosis, even after adjusting for confounding variables. This may suggest that fibrosis is primarily linked with impaired left-sided measures of cardiac structure and function.Linear Regression ModelsCubic Spline Curves