This clinical, observational and case-control study was conducted at the COPD outpatient clinic of the Hospital das Clínicas, Federal University of Minas Gerais, Belo Horizonte, Brazil. It was reviewed and approved by the local ethics committee. All participants provided written informed consent.

Twenty COPD patients and 20 controls matched for sex and age were included in the study, as illustrated in Figure 1 . The inclusion criteria for all participants were: ≥ 40 years of age, no history of asthma, and no known significant cardiovascular disease (especially coronary artery disease, heart failure, or complex arrhythmias). COPD patients had to be current or previous smokers with a history of at least 20 pack-years and airway obstruction classified as GOLD II-IV. The exclusion criteria were exacerbation in the previous 30 days and clinical signs of cor pulmonale .

All participants underwent a complete clinical evaluation by a pulmonologist, including other reported health problems. Hemoglobin, fasting blood glucose, renal function tests, electrocardiography, and chest x-rays were obtained from all participants and were used to exclude other serious diseases.

For all participants, the same technician performed spirometry with a Koko spirometer (2002 Pulmonary Data Services Instrumentation, Louisville, CO, USA). The absolute values and percentages of post-bronchodilator forced expiratory volume in 1 second and vital capacity were obtained from all participants according to Brazilian guidelines and reference values.¹⁰ All participants performed the 6-minute walk test twice according to American Thoracic Society guidelines,¹¹ and the greatest distance covered was used in the analysis.

All participants underwent a comprehensive transthoracic echocardiographic examination according to American Society of Echocardiography recommendations⁹ using a Vivid 7 imaging system (GE Vingmed Ultrasound, Horten, Norway). For all parameters, the analysis considered the mean of three measurements taken by two experienced echocardiographers blinded to the patients’ medical history.

The M-mode values provided 1D diameters (in millimeters) of the aorta, left atrium, right ventricle in diastole, left ventricle (LV) in diastole, and systole, and the inferior vena cava. The interventricular septum and LV posterior wall were also measured. RV free wall thickness was measured (in millimeters) at end diastole with 2D-oriented M-mode imaging in a subcostal view. Tricuspid annular plane systolic excursion (TAPSE) was obtained in M-mode, guided by a focused 2D apical 4-chamber examination. LV volumes at end diastole and systole and LV ejection fraction (EF) were measured using the Teichholz method (M-mode) to assess LV systolic function. LVEF was also obtained by a 2D examination using the Simpson method. RV linear measurements were taken using 2D imaging, including the RV basal dimension and RV mid-cavity from the apical 4-chamber view. RV dimension was also measured in the parasternal short and long axis views. Peak tricuspid regurgitant jet velocity and pulmonary artery systolic pressure were measured with color Doppler; continuous-wave Doppler was used in an attempt to obtain better alignment of the regurgitant jet.

Special adjustments were made to measure myocardial deformation values (strain/strain rate) in tissue Doppler. To obtain the highest possible frame rate, ≤ 30° reduction was used, as well as depth reduction. The tilt feature was used for better alignment to keep the RV wall at the center of the ultrasound sector.

Simultaneously, an appropriate adjustment of the speed range setting was used to prevent aliasing. Three complete consecutive cardiac cycles were observed in the apical 4-chamber view (emphasizing the RV) and were digitally recorded and stored. The frame rate for all participants was ≥ 150/s. The digitized images were transferred to a computer and analyzed using Echo PAC GE software (PCTM by SW, version 110.1.0; Vingmed Ultrasound Horten, Norway).

Global longitudinal strain (GLS) was measured with speckle tracking using 2D image motion in the apical four-chamber view according to current recommendations.^{7 , 8} Three cardiac cycles were obtained in the RV-focused apical four-chamber window. We attempted to obtain the best image without interference, using a frame rate of 60-80/s. GLS was measured using a 6-segment RV model (including interventricular septum and RV free wall). The data were sent to a separate workstation (EchoPAC version 112.1.3., GE Healthcare) for further offline analysis.

For data acquisition, real-time 3D echocardiograms were used with the full-volume pattern, which was obtained with a matrix-array transducer. Post-processing analyses (4D RV-FUNCTION; TomTec Imaging Systems GmbH, Unterschleissheim, Germany) were performed with semi-automatic software, which traced the predefined RV borders to detect the endocardial contour. This allowed measurement of the RV end-diastole, RV end-systole, and RV stroke volume (RVSV).

Statistical analyses were performed using IBM SPSS Statistics version 18 (IBM, Armonk, NY, USA). Categorical variables were expressed as frequencies. Continuous and normally-distributed variables were expressed as means and standard deviations (SD) and compared using Student’s t-test for independent samples. Non-normally distributed variables were compared using the Mann-Whitney test and were expressed as median (1^st; 3^rd quartiles). The normality of the variables was assessed with the Shapiro-Wilk test. Associations between categorical variables were determined with Fisher’s exact test. P <0.05 was considered statistically significant for all measurements.

The echocardiographic values for 10 variables from 5 randomly chosen COPD patients and 5 controls were reanalyzed by both observers ≥ 20 days after the first evaluation. These patients were selected by randomly drawing numbered slips of paper representing the two exam groups, without comparing them to previous results. Means and SDs were obtained for every patient based on two measurements of each variable. Intra- and interobserver variability were then determined as a percentage of the mean ± SD of all results for each variable. Bland-Altman plots were also used for GLS and RVEF.

The general characteristics of the patients with stable COPD and respective controls are shown in Table 1 .

The sample consisted primarily of older men. No participants presented comorbidities. The weight difference was smaller in the COPD group than the control group (63.0 ± 12.3 vs 70.6 ± 10.8 kg, p = 0.046). Total pack-years and several comorbidities were predictably higher in the COPD group. There were no significant differences between the groups for the other general characteristics.

Table 2 compares the M-mode, 2D, and Doppler echocardiography results for the COPD and control groups.

The only M-mode parameters that differed significantly between the groups were TAPSE and RV free wall thickness. Only 30% of the COPD group had a normal RV free wall thickness (considering 5 mm as the cut-off point). All LV anatomical and functional parameters in M-mode were within normal limits and were similar between groups. In 2D echocardiography, the linear dimensions of the RV did not differ significantly between the COPD and control groups. However, patients with lung disease had significantly higher peak regurgitant jet velocity and pulmonary artery systolic pressure values than controls.

RVEF and RVSV were significantly lower in the COPD group. All deformation indices (strain/strain rate) were significantly lower in all segments in the COPD group, which indicates reduced regional deformation that affects the RV free wall. GLS also differed significantly between the groups, indicating RV dysfunction in the COPD group ( Figure 2 and Table 3 ).

The RVEF difference between groups was highly significant. RVSV also differed significantly between the groups, showing that 3D echocardiogram can identify RV dysfunction in stable COPD patients. ( Figure 3 and Table 3 ).

Only one COPD patient (5%) showed no changes related to the significantly different echocardiographic variables (RV end-diastole, TAPSE, pulmonary artery systolic pressure, GLS, and RVEF). Two patients (10%) differed in only one parameter (one with reduced GLS, the other with reduced RVEF). Nine other patients (45%) showed changes in either four or five of these variables.

Table 4 shows the intra- and interobserver variability for the main variables. Figure 4 shows the Bland-Altman plots for RV functional variables, GLS, and RVEF.

This study has some limitations. When selecting COPD patients, no specific exams were performed to exclude other causes of RV dysfunction (such as pulmonary thromboembolism or subclinical coronary artery disease), although no clinical, electro-, or echocardiographic evidence of these diseases was found.

Two-dimensional strain involves some limitations that should be considered⁷ . The analysis software was designed to evaluate LV systolic function and was adapted for the RV. The RV chamber has a thin wall and a more complex shape than the LV, with different inlet and outlet different planes. These anatomical features complicate selecting the width of the region of interest and tracking speckles frame by frame.

Although our sample of COPD patients was too small to draw generalized conclusions, the study could generate new research questions and propaedeutic investigations. The current literature on determining RV function through deformation indices in COPD patients is scarce.