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Chronic obstructive pulmonary disease (COPD) is a highly prevalent, complex and underdiagnosed disease. Progressive deterioration and unfavorable outcomes are expected if the disease is not adequately recognized and treated. It is believed that echocardiography could provide more information on the prognosis of the disease considering other morphological and biventricular function variables.
The correlation of the enlargement of right chambers with worse prognostic parameters in COPD was described in many studies. Nevertheless, the value of right chambers in the prediction of unfavorable outcomes in this disease is not well established in the literature.
The aim of this study was to identify cutoff points for echocardiographic markers as potential predictors of adverse outcomes, such as death, non-fatal cardiovascular events and hospitalization in COPD patients during a 1-year follow-up and to assess the impact of these markers in anticipating fatal and nonfatal events.
The study followed the Declaration of Helsinki and was approved by the Human Research Ethics Committee of the Federal University of São Carlos (protocol number: 91088318.7.1001.5504). All volunteers signed a written informed consent statement prior to inclusion in the study.
Patients 40 years or older with COPD and preserved left ventricle (LV) ejection fraction (EF) in the echocardiogram (LVEF>50%) were included in the study. COPD was defined as the presence of respiratory symptoms (dyspnea, chronic cough, or sputum production), actual or past positive risk factors (tobacco and/or biomass fuel smoke exposures) and a post bronchodilator spirometry exhibiting a forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio below 0.7.
Initially, for the clinical and diagnostic stratification, the COPD patients underwent a 2D-echocardiogram using an ultrasound device “Affiniti 50” (Philips, USA) with a 2–4 MHz transducer and tissue Doppler imaging software. Quantifications of the cardiac chambers were performed according to the American Society of Echocardiography (16). LV diastolic diameter (LVDD), left atrium volume (LAV), right atrium volume (RAV), indexed LV mass (ILVM), relative wall thickness (RWT) and basal right ventricle diastolic diameter (RVDD) were quantified. RV dimension was estimated according to recent guidelines (16) from a RV-focused apical four-chamber view obtained with either lateral or medial transducer orientation.
Patients were included and accompanied during a 12-month period by telephone calls and routine medical consultation with their home or family caregiver and investigated for primary endpoints: death, hospitalization or non-fatal cardiovascular event (heart failure, myocardial infarction and/or stroke). Medical records of these patients were also assessed during telephone calls and consultation.
Statistical analysis: SigmaPlot 12.0 (SigmaPlot Software, California, USA) package was used for data analysis. Comparisons between patients with or without primary endpoints were performed using the Chi-Square and Fisher test for categorical variables and T test for variables with normal distribution and Man-Whitney for variables with non-parametric distribution. First, receiver operating characteristic (ROC) curve analyses selected the optimal threshold values to differentiate the primary endpoints considering echocardiographic variables.
The confidence interval (95% CI) was used to determine the ability of the clinical variables, with the lower limit being greater than 0.50. Subsequently, the cutoff points of the variables that obtained significant areas under the ROC curve were identified with the respective values of sensitivity and specificity. Kaplan-Meier was obtained to explore the impact of RVDD ≥38 mm and <38 mm (log-Rank), according to ROC cutoff point in the primary endpoints.
Regarding the results, Table 1 shows the baseline and clinical characteristics of the patients considering the division of those with and without primary endpoints over a 1-year follow-up. No differences were found in the baseline characteristics, clinical and medication use. Patients who suffered at least one primary endpoint had reduced FVC (%; p = 0.03), lower LVEF (p = 0.01), although still within the normal range, and an increased RVDD (p = 0.03) and RAV (p = 0.03).
TABLE 1Comparison of COPD patients with and without primary endpoints over a 1-year follow-up.
Yes (n = 10)
No (n = 25)
70 ± 10
65 ± 7
Male, n (%)
Medications, n (%)
50 ± 16
65 ± 21
2.4 ± 0.7
3.1 ± 1.2
73 ± 17
92 ± 20
0.52 ± 0.09
0.52 ± 0.11
40 ± 9
33 ± 8
0.9 ± 0.3
1.2 ± 0.45
E’ Mitral, cm/s
E’ Tricuspid, cm/s
15 ± 9
21 ± 4
50 ± 18
49 ± 10
56 ± 9
64 ± 9
Values presented as mean ± standard deviation for normally distributed variables or median and interquartile range for non-parametric variables or number (N), and percentage (%). COPD: chronic obstructive pulmonary disease;; FEV1: forced expiratory volume in the first second; FVC: forced vital capacity; LVDD: left ventricular diastolic diameter; RVDD: right ventricle diastolic diameter; RWT: relative wall thickness; ILVM: indexed left ventricular mass index; LAV = indexed left atrial volume; RAV = right atrium volume; E: E-wave peak velocity in the Mitral or Tricuspid rapid filling phase; A: A-wave peak velocity in the mitral or tricuspid atrial contraction phase; E’ mitral = mean displacement velocity of the septal and lateral mitral annulus in the rapid filling phase; Tricuspid E’: displacement velocity of the tricuspid lateral annulus in the rapid filling phase; TAPSE= tricuspid annular plane systolic excursion; FAC: right ventricle fractional area change; LVEF = LV ejection fraction. Comparison based on Chi-square for N(%) and T Test or Man-Whitney for mean and median, respectively, Significance level p < 0.05.
According to Roc curve, as shown in Fig. 1, RVDD was the unique variable with area under the curve (AUC) of 0.73 (95% CI: 0.52-0.93; p = 0.03) and a cut-of-point ≥38 mm demonstrating a sensitivity of 80% and a specificity of 40% for the prediction of unfavorable outcome. In the Kaplan-Meier analysis, patients with COPD and RVDD ≥38 mm have a higher probability for unfavorable outcomes when compared to those with RVDD ≥38 mm after a 12-month period of follow up. The primary endpoints curve differed significantly in the log-rank test (p = 0.03).
The main findings of the study were that patients with an unfavorable outcome at 1-year follow-up had lower LVEF, increased RVDD and RAV. The accuracy of RVDD with a value greater than 38mm for prediction of unfavorable outcome was 73%, with 80% sensitivity and 40% specificity.
In this context, the greatest contribution of this study, for the physicians and multidisciplinary team that assist COPD patients, is the possibility to identify, through echocardiography and with good accuracy, which patients are predicted to have adverse outcome and perhaps pursue a more aggressive therapeutic approach.
In conclusion, RVDD greater than 38 mm was 73% accurate in predicting unfavorable outcomes (death, hospitalization or non-fatal cardiovascular events) over a 1-year follow-up. These findings reinforce that echocardiography may be a useful and noninvasive tool in clinical settings and assessing the prognosis of these patients.
Source of Funding
This study was supported by a research grant from Fundação de Amparo à Pesquisa do Estado de São Paulo, São Paulo, Brazil (FAPESP) Process N° (2015/26/501-1 and N° 2018/03233-0) and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior- Brasil (CAPES - 001) and CNPq: 141803/2019 -3.
Comparison of echocardiographic markers of right ventricular function in determining prognosis in chronic pulmonary disease.