Affiliations
doi: 10.29271/jcpsppg.2025.01.122ABSTRACT
Objective: To evaluate the diagnostic accuracy of transthoracic echocardiography (TTE) and biomarkers [B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)] in detecting pulmonary arterial hypertension (PAH) among patients with chronic obstructive pulmonary disease (COPD), using right heart catheterisation (RHC) as the gold standard.
Study Design: A cross-sectional study.
Place and Duration of the Study: Department of Pulmonology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from July to December 2024.
Methodology: A total of 300 patients with COPD, aged 40–80 years, were recruited through a non-probability consecutive sampling technique. Patients with malignancy, severe cardiopulmonary compromise, massive pleural effusion, or vertebral deformities were excluded. Data were analysed using SPSS version 23, and diagnostic parameters, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated for TTE and biomarkers. Categorical variables were expressed as frequencies and percentages, while continuous variables were presented as mean ± SD.
Results: RHC confirmed PAH in 90 (30%) patients. TTE demonstrated a diagnostic accuracy of 47.0%, with a sensitivity of 86.7%, specificity of 30.0%, PPV of 34.7%, and NPV of 84.0%. Biomarkers achieved a higher overall accuracy (71.0%), with a sensitivity of 73.3%, specificity of 70.0%, PPV of 51.2%, and NPV of 85.7%. Compared with TTE, biomarkers showed superior specificity but reduced sensitivity.
Conclusion: Both TTE and biomarkers provide moderate diagnostic accuracy in detecting PAH in patients with COPD. TTE is more sensitive, whereas biomarkers are more specific. A combined approach may improve early detection while reducing reliance on invasive RHC, which remains the definitive diagnostic modality.
Key Words: Pulmonary hypertension, Chronic obstructive pulmonary disease, Biomarkers, Right heart catheterisation, Transthoracic echocardiography.
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition that causes persistent, irreversible airflow obstruction and persistent respiratory symptoms such as coughing, sputum production, and dyspnoea.1 The primary cause of COPD is prolonged exposure to noxious gases or airborne particles, with cigarette smoke recognised as the leading risk factor. Globally, COPD is a leading cause of morbidity and mortality, with an increasing disease burden projected in the coming decades.2,3
Beyond its respiratory manifestations, COPD is frequently associated with systemic complications and comorbidities that contribute to poor clinical outcomes.4 Among these, pulmonary arterial hypertension (PAH) has emerged as a significant prognostic determinant.5 Haemodynamically, PAH in COPD is defined as a mean pulmonary arterial pressure (mPAP) of ≥25 mmHg at rest, as verified by right heart catheterisation (RHC), the gold standard for diagnosis at the moment.6-8 The presence of PAH in COPD patients is associated with increased hospitalisations, reduced exercise tolerance, and higher mortality rates.9,10 However, the true prevalence of PAH in this population remains uncertain and likely underdiagnosed, especially in the early stages.11
The clinical recognition of PAH in patients with COPD is challenging because of overlapping symptoms and the absence of specific clinical markers.10 While RHC provides definitive haemodynamic assessment, its invasive nature, cost, and associated risks limit its routine use in clinical practice.11 Therefore, there is a growing interest in non-invasive diagnostic alternatives.
Transthoracic echocardiography (TTE) and circulating biomar-kers such as B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT proBNP), which indicate right ventricular strain, provide promising non-invasive options for risk stratification and early detection because of their accessibility and capacity to estimate pulmonary artery pressures.12,13
Despite their potential, the diagnostic performance of TTE and biomarkers in detecting PAH among COPD patients remains variable and incompletely defined. Previous studies have reported high sensitivity but limited specificity for TTE, whereas biomarkers have shown potential for ruling out the disease in low-risk individuals.12 However, comparative data assessing their accuracy against RHC in patients with COPD are limited.
This study aimed to assess the diagnostic precision of cardiac biomarkers and TTE in detecting PAH in patients with COPD, using RHC as the reference standard. By determining their sensitivity, specificity, predictive values, and overall diagnostic accuracy, this research seeks to inform clinical decision-making and enhance early identification of PAH in COPD patients.
METHODOLOGY
This cross-sectional study was conducted at the Department of Pulmonology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from July to December 2024. Ethical approval was obtained from the Institutional Research Review Committee of Pakistan Institute of Medical Sciences, Islamabad, Pakistan.
A total of 300 patients were recruited using a non-probability consecutive sampling technique. The sample size was calculated based on an assumed PAH prevalence of 20% among COPD patients, with anticipated sensitivity and specificity of biomarkers at 81.4% and 87.5%, respectively. A 10% margin of error and a 95% confidence level were used in the calculations.
Eligible participants were between the ages of 40 and 80 years, of either gender, and had a confirmed diagnosis of COPD by spirometry. Individuals with conditions that could interfere with diagnostic accuracy, such as malignant lung diseases, severe cardiopulmonary compromise, massive pleural effusion, or significant vertebral deformities based on clinical evaluation, medical history, and imaging findings, were excluded.
Written informed consent was obtained from all patients included in the study. Baseline data, including age, gender, body mass index (BMI), and smoking history, were recorded. A 5 cc venous blood sample was drawn from each participant to measure BNP and NT-proBNP levels. Plasma concentrations of BNP were analysed using a chemiluminescent microparticle immunoassay (CMIA), while NT-proBNP levels were quantified with an electrochemiluminescence immunoassay (ECLIA) in the hospital laboratory, following the manufacturer’s standard protocols. TTE was performed by a consultant cardiologist using TOSHIBA® systems equipped with variable frequency transducers ranging from 1.7 to 2.2 MHz. RHC was performed by a different consultant cardiologist on different days, and RHC was used as the reference standard for diagnosing PAH.
Statistical analysis was carried out using IBM SPSS Statistics version 23. Descriptive statistics were used to summarise data: Categorical variables such as gender and smoking status were presented as frequencies and percentages, while continuous variables such as age and BMI were expressed as means with standard deviations. Diagnostic metrics, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TTE and biomarkers, were calculated with RHC findings as the gold standard for comparison. For all diagnostic accuracy parameters, 95% confidence intervals (CIs) were computed to assess the precision of estimates. A p-value of <0.05 was considered statistically significant.
RESULTS
In this study, 300 participants were enrolled, comprising 187 males (62.3%) and 113 females (37.7%). The participants had a mean age of 59.76 ± 13.48 years. The average BMI was 26.35 ± 4.26 kg/m2, with values ranging from 17.5 kg/m2 to 33.5 kg/m2 (Table I).
Among 300 participants, RHC confirmed PAH in 90 (30%) participants, while 210 (70.0%) had no PAH. TTE identified 225 cases as positive for PAH and 75 as negative. Among the 90 PAH-positive patients confirmed by RHC, TTE correctly identified 78 (true positive) but missed 12 (false negative), resulting in a sensitivity of 86.7%. Among the 210 patients with no PAH, TTE correctly classified 63 as negative (true negative) but misclassified 147 as positive (false positive), yielding a specificity of 30.0%. The PPV of TTE was 34.7%, while the NPV was 84.0%. Overall, the diagnostic accuracy of TTE for detecting PAH was 47.0% (Table II).
Biomarkers identified 164 patients as positive for PAH and 136 as negative. Of the 90 PAH-positive patients confirmed by catheterisation, biomarkers correctly identified 66 (true positive) but missed 24 (false negative), resulting in a sensitivity of 73.3%. For the 210 patients with no PAH, biomarkers correctly classified 147 as negative (true negative) but misclassified 63 as positive (false positive), yielding a specificity of 70.0% (Table III). The PPV of biomarkers was 51.2%, while the NPV was 85.7%. The overall diagnostic accuracy of biomarkers for detecting PAH was 71.0% (Table IV).
When comparing echocardiography and biomarkers for the detection of PAH, TTE demonstrated a higher sensitivity (86.7% vs. 73.3%) but a lower specificity (30.0% vs. 70.0%) compared to biomarkers. Biomarkers demonstrated a slightly higher NPV (85.7% vs. 84.0%) and superior overall diagnostic accuracy (71.0% vs. 47.0%, Table IV).
Table I: Demographic characteristics of participants.
|
Variables |
Values |
|
Total participants |
300 |
|
Male |
187 (62.3%) |
|
Female |
113 (37.7%) |
|
Mean age (years) |
59.76 ± 13.48 |
|
Mean BMI (kg/m2) |
26.35 ± 4.26 |
Table II: Diagnostic performance of TTE for detection of PAH using RHC as the reference standard.
|
Parameters |
PAH on TTE: Positive |
PAH on TTE: Negative |
Total |
|
PAH on cardiac cath: present |
78 (true positive) |
12 (false negative) |
90 |
|
PAH on cardiac cath: absent |
147 (false positive) |
63 (true negative) |
210 |
|
Total |
225 |
75 |
300 |
Table III: Diagnostic performance of biomarkers for detecting PAH.
|
Parameters |
PAH on biomarkers: Positive |
PAH on biomarkers: Negative |
Total |
|
PAH on cardiac cath: Present |
66 (true positive) |
24 (false negative) |
90 |
|
PAH on cardiac cath: Absent |
63 (false positive) |
147 (true negative) |
210 |
|
Total |
164 |
136 |
300 |
Table IV: Comparison of diagnostic performance for echocardio- graphy and biomarkers.
|
Measure |
Echocardiography |
Biomarkers |
|
Sensitivity |
86.7% |
73.3% |
|
Specificity |
30.0% |
70.0% |
|
PPV |
34.7% |
51.2% |
|
NPV |
84.0% |
85.7% |
|
Diagnostic accuracy |
47.0% |
71% |
DISCUSSION
The purpose of this study was to assess the diagnostic precision of TTE and biomarkers (BNP and NT proBNP) for PAH in COPD patients, using RHC as the gold standard. The findings of this study shed important light on the advantages and disadvantages of these diagnostic instruments in a clinical context.
In this study, 90 COPD patients were diagnosed with PAH using RHC, consistent with previous findings on its high prevalence in COPD.14 A well-known comorbidity of COPD is PAH, whose incidence varies from 20 to 90% depending on the demographic and diagnostic standards.15 The prevalence in this study reflects the severity of COPD in this cohort, as patients with advanced stages of COPD are more likely to develop PAH due to the progression of pulmonary vascular remodelling.16 Recognising this high prevalence emphasises the need for effective screening and early diagnosis of PAH in COPD patients to prevent worsening of disease outcomes.
TTE demonstrated a sensitivity of 86.7% for detecting PAH, which is consistent with studies that report TTE as a sensitive diagnostic tool for PAH.17-19 This high sensitivity suggests that echocardiography is capable of identifying the majority of patients with PAH, making it a useful screening tool in clinical practice. However, the specificity of TTE in the current study was low (30.0%), indicating a high false-positive rate.20 While TTE is an excellent initial tool for PAH detection, its limited specificity warrants the use of more definitive diagnostic tests, such as RHC, to confirm the diagnosis.
The biomarkers (BNP and NT proBNP) demonstrated a sensitivity of 73.3% and a specificity of 70.0% in detecting PAH. These results are consistent with the existing literature, which suggests that biomarkers can serve as useful screening tools for PAH, but they are not definitive in diagnosis.21 The sensitivity of biomarkers is high, indicating their reliability in identifying patients with PAH. However, their moderate specificity indicates that there is a risk of false-positive results, particularly in patients with conditions that can elevate BNP levels, such as left ventricular dysfunction or renal disease. While biomarkers offer a non-invasive screening method for PAH, their utility may be limited in distinguishing PAH from other causes of elevated BNP levels, emphasising the need for confirmatory testing with RHC.
In comparing TTE and biomarkers, both tools demonstrated moderate diagnostic performance. Echocardiography showed a higher sensitivity of 86.7% than biomarkers (73.3%), suggesting that it may be more effective at detecting PAH. However, biomarkers had a higher specificity of 70.0% compared to echocardiography (30.0%), which may help reduce the false-positive rate in patients without PAH. Using echocardiography for initial screening, followed by biomarker testing, may offer a more comprehensive diagnostic strategy for PAH, potentially reducing the need for invasive procedures in many patients.
The results from this study highlight the importance of using a multi-faceted approach for diagnosing PAH in COPD patients. Both TTE and biomarkers demonstrate moderate diagnostic utility, but their limitations in specificity necessitate confirmatory testing with RHC. Given the non-invasive nature of TTE and biomarkers, these tools can serve as valuable initial screening methods, but they should be followed by RHC for definitive diagnosis. This approach may help reduce the number of invasive catheterisation procedures while still ensuring accurate diagnosis and optimal patient care.22,23
Although this study offers valuable information about the diagnostic precision of biomarkers and echocardiography, it has a number of limitations. First, since the study was conducted in a single centre, it may not be generalisable to other groups. Second, RHC is an intrusive treatment with hazards, although it is the gold standard for diagnosing PAHs. It would be advantageous to conduct larger, multicentre studies in the future to confirm these results and to investigate different non-invasive diagnostic approaches for PAH.
CONCLUSION
Echocardiography and biomarkers (BNP and NT proBNP) demonstrate moderate diagnostic performance in detecting PAH in patients with COPD. TTE, with its high sensitivity but low specificity, can effectively screen for PAH, while biomar-kers show moderate sensitivity and specificity. However, confirmatory testing with RHC remains essential for a definitive diagnosis. A combined approach using both TTE and biomarkers, followed by confirmatory catheterisation, may offer a more comprehensive and efficient diagnostic path-way for PAH in COPD patients.
ETHICAL APPROVAL:
Ethical approval was obtained from the Ethical Review Committee of the Pakistan Institute of Medical Sciences, Islamabad, Pakistan.
PATIENTS’ CONSENT:
Written informed consent was obtained from all participants.
COMPETING INTEREST:
The authors declared no conflict of interest.
AUTHORS’ CONTRIBUTION:
HA: Conception, data curation, and writing of the original draft.
SAS: Supervision.
MN: Writing of the original draft and formal analysis.
MAZ: Writing of the original draft.
UR, SGB: Writing, review, and editing.
All authors approved the final version of the manuscript to be published.
REFERENCES