European Journal of Cardiovascular Medicine

Pulmonary hypertension (PH) is a progressive and potentially fatal condition characterized by elevated pulmonary arterial pressure, leading to right ventricular dysfunction, decreased exercise capacity, and eventually right heart failure. It is a complex, multifactorial syndrome that can arise as an idiopathic disorder, a genetic condition, or more commonly, as a complication of underlying cardiopulmonary diseases. Among these, interstitial lung diseases (ILDs) are particularly important contributors, as the chronic parenchymal injury, inflammation, and fibrotic remodeling that define ILD often lead to pulmonary vascular remodeling and PH. The coexistence of PH in ILD significantly worsens morbidity, impairs quality of life, and increases mortality, making it a critical area of investigation.^[1]

Interstitial lung disease is an umbrella term encompassing a wide range of parenchymal lung disorders such as idiopathic pulmonary fibrosis (IPF), sarcoidosis, connective tissue disease-associated ILD, and hypersensitivity pneumonitis. These conditions share the pathological hallmark of alveolar inflammation progressing to fibrosis, which distorts lung architecture and impairs gas exchange. Chronic hypoxemia and destruction of capillary beds in ILD cause sustained vasoconstriction of pulmonary arterioles, endothelial dysfunction, and ultimately structural remodeling of the pulmonary vasculature. The result is an increase in pulmonary vascular resistance and pulmonary artery pressure, culminating in PH. Importantly, PH in ILD patients is associated with reduced exercise tolerance, early desaturation during exertion, greater need for supplemental oxygen, increased hospitalization, and decreased survival compared to ILD patients without PH.^[2]

The reported prevalence of PH in ILD varies considerably, largely due to differences in study populations, diagnostic methods, and definitions of PH. Right heart catheterization (RHC) remains the gold standard for diagnosis, but its invasive nature, limited availability, and risk of complications make it unsuitable for routine screening. Echocardiography has therefore become the preferred non-invasive tool for initial assessment of pulmonary pressures. It allows estimation of systolic pulmonary artery pressure (sPAP), evaluation of right heart size and function, and identification of secondary signs of PH. While echocardiography has limitations, it remains invaluable for screening, risk stratification, and longitudinal follow-up of ILD patients in clinical practice.^[3]

Globally, several studies have demonstrated that the prevalence of PH in ILD ranges from 30% to 50%, with higher rates observed in patients with advanced disease or awaiting lung transplantation. The presence of PH in ILD is not merely an epiphenomenon of advanced fibrosis but represents an independent prognostic factor. Even mild to moderate increases in pulmonary artery pressure can disproportionately worsen symptoms and outcomes. This underscores the need for timely recognition and appropriate management. Therapeutic options remain limited: antifibrotic agents slow ILD progression, while oxygen therapy alleviates hypoxemia, but specific PH-directed therapies (such as endothelin receptor antagonists or phosphodiesterase-5 inhibitors) have shown mixed results and are not universally recommended. Thus, early detection and careful monitoring remain crucial.^[4]

In India, where ILD prevalence is rising due to environmental exposures, occupational risks, and autoimmune diseases, PH complicating ILD represents an underexplored yet clinically significant problem. Limited regional data exist regarding the prevalence and echocardiographic profiles of PH in Indian ILD patients. This knowledge gap hampers early identification and risk stratification in population. A cross-sectional echocardiographic study therefore provides an opportunity to bridge this gap, quantify the prevalence of PH among ILD patients, and highlight the need for systematic evaluation in tertiary care settings.^[5]

Aim

To determine the prevalence of pulmonary hypertension in patients with interstitial lung disease using echocardiography.

Objectives

1. To estimate the prevalence of pulmonary hypertension in patients diagnosed with interstitial lung disease.
2. To assess the echocardiographic parameters associated with pulmonary hypertension in ILD patients.
3. To correlate pulmonary hypertension with clinical and demographic characteristics of ILD patients.

Source of Data

The data were obtained from patients diagnosed with interstitial lung disease attending the Department of Pulmonary Medicine and referred to the Department of Cardiology for echocardiographic evaluation.

Study Design

This was a hospital-based, cross-sectional observational study.

Study Location

The study was conducted at the Department of Pulmonary Medicine and Cardiology a tertiary care teaching hospital.

Study Duration

The study was carried out over a period of 12 months from May 2023 to May 2024.

Sample Size

A total of 140 patients diagnosed with ILD were included in the study.

Inclusion Criteria

• Patients aged ≥18 years with a clinical, radiological, and/or histopathological diagnosis of ILD.
• Patients willing to provide informed consent.

Exclusion Criteria

• Patients with known congenital heart disease or primary pulmonary arterial hypertension.
• Patients with significant left heart disease (e.g., left ventricular systolic dysfunction, severe valvular heart disease).
• Patients with chronic thromboembolic pulmonary hypertension.
• Patients unwilling to participate.

Procedure and Methodology

All patients fulfilling the eligibility criteria were enrolled consecutively. A detailed clinical history including age, sex, smoking history, occupational exposure, and comorbidities was obtained. Physical examination findings, baseline vital signs, and oxygen saturation were recorded.

High-resolution computed tomography (HRCT) chest findings confirming ILD were documented from case records. All participants underwent transthoracic echocardiography performed by a cardiologist using a standardized protocol. The estimation of systolic pulmonary artery pressure (sPAP) was done using Doppler assessment of tricuspid regurgitation jet velocity along with right atrial pressure estimation. Patients were classified as having PH if estimated sPAP was >35 mmHg. Additional echocardiographic parameters such as right atrial size, right ventricular size and function, interventricular septal motion, and inferior vena cava collapsibility were also noted.

Sample Processing

No biological sample processing was required for this study. Data were collected from clinical evaluation, HRCT findings, and echocardiographic examination.

Statistical Methods

Data were entered into Microsoft Excel and analyzed using SPSS (version 27.0). Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as frequencies and percentages. Chi-square test was applied to assess associations between categorical variables, and Student’s t-test was used for continuous variables. Logistic regression was employed to identify independent predictors of pulmonary hypertension. A p-value <0.05 was considered statistically significant.

Data Collection

All relevant clinical, radiological, and echocardiographic data were recorded on a predesigned case record form. Data accuracy was cross-checked by two investigators. Confidentiality of patient records was maintained throughout the study.

Table 1: Overall prevalence and key echo metrics (N = 140)

Table 1 summarizes the overall prevalence of pulmonary hypertension (PH) in patients with interstitial lung disease (ILD). Out of 140 patients included in the study, 48 were found to have echocardiographically defined PH, giving a prevalence of 34.3% (95% CI: 26.9-42.5). The mean systolic pulmonary artery pressure (sPAP) across the study population was 37.1 ± 6.0 mmHg, while the mean tricuspid regurgitation (TR) velocity was 2.71 ± 0.34 m/s.

Table 2: Prevalence of PH by ILD subtype (N = 140)

Table 2 presents the prevalence of PH across different ILD subtypes. Patients with idiopathic pulmonary fibrosis (IPF) demonstrated the highest prevalence, with 20 of 39 cases (51.3%, 95% CI: 36.2-66.1) affected. In connective tissue disease-associated ILD (CTD-ILD), the prevalence was 31.2% (10/32 cases), while hypersensitivity pneumonitis (HP) showed a prevalence of 25.9% (7/27 cases). Sarcoidosis had the lowest proportion, with only 16.7% (3/18 cases) affected, whereas 33.3% of patients with NSIP/other ILDs had PH. The overall chi-square test did not reach statistical significance (χ²=8.46, df=4, p=0.0762).

Table 3: Echocardiographic parameters associated with PH

Table 3 details the echocardiographic parameters associated with PH in ILD patients. Those with PH had a markedly elevated mean sPAP (52.7 ± 8.1 mmHg) compared to non-PH patients (28.9 ± 4.6 mmHg), with a highly significant mean difference of 23.8 mmHg (95% CI: 21.3-26.3, p<0.0001). Similarly, TR velocity was significantly higher in PH patients (3.30 ± 0.40 vs. 2.42 ± 0.33 m/s; p<0.0001). Right ventricular (RV) basal diameter was increased (42.1 ± 5.3 vs. 36.5 ± 4.8 mm; p<0.0001), while tricuspid annular plane systolic excursion (TAPSE) was reduced in PH patients (15.8 ± 2.9 vs. 19.6 ± 3.1 mm; p<0.0001), indicating impaired RV systolic function. Categorical indices also revealed significant associations: RA area ≥18 cm² was present in 52.1% of PH patients versus 13.0% without PH (RR=3.99, p<0.0001), and RV dysfunction defined by fractional area change <35% was observed in 37.5% of PH patients compared to 6.5% in non-PH patients (RR=5.75, p<0.0001).

Table 4: Correlation of PH with clinical & demographic variables

Table 4 correlates PH with clinical and demographic characteristics. Patients with PH were older (61.7 ± 9.6 vs. 58.1 ± 10.4 years; p=0.043) and had longer disease duration (3.8 ± 2.1 vs. 2.9 ± 1.8 years; p=0.014). They performed significantly worse on the 6-minute walk test (294.0 ± 68.0 vs. 362.0 ± 74.0 m; p<0.0001) and had lower resting oxygen saturation (91.7 ± 3.6 vs. 94.1 ± 2.9%; p=0.0001). Diffusing capacity (DLCO % predicted) was also significantly reduced in PH patients (37.4 ± 9.5 vs. 44.6 ± 10.8; p=0.0001). Although male sex and smoking were more frequent among PH patients, these did not reach statistical significance (p=0.244 and p=0.053, respectively). The presence of a UIP pattern on HRCT trended towards significance (p=0.095). Notably, long-term oxygen therapy (LTOT) use was significantly more common among PH patients (35.4% vs. 14.1%; RR=2.51, p=0.0036).

In this cross-sectional ILD cohort (N=140), one in three patients met echocardiographic criteria for pulmonary hypertension (PH): 48/140 (34.3%, 95% CI 26.9-42.5). This prevalence aligns with contemporary syntheses reporting PH-ILD in roughly 15-40% of unselected ILD populations and substantially higher proportions in advanced disease or transplant cohorts. Reviews summarizing multi-study data describe early-stage prevalence as low as 3-15% but rising steeply with disease progression-approaching or exceeding 50% in severe ILD and up to 60-90% among lung-transplant candidates-patterns consistent with point estimate falling between mild-moderate and advanced disease populations. Maher TM. (2024)^[6]

Subtype analysis mirrored the known heterogeneity across ILDs. IPF carried the numerically highest PH burden (51.3%; 95% CI 36.2-66.1), whereas sarcoidosis exhibited the lowest (16.7%; 95% CI 5.8-39.2); CTD-ILD and HP occupied intermediate ranges, and NSIP/other tracked near the overall average. Although the omnibus χ² test did not reach significance (p=0.076), the rank order is concordant with prior reports in which IPF repeatedly shows the greatest propensity for pulmonary vascular involvement. Historic single-center series of advanced IPF reported PH in roughly one-third of patients, with much higher figures in transplant wait-list cohorts, supporting observation that disease mix and severity strongly influence measured prevalence. Nikkho SM et al.(2022)^[7]

Echocardiographic markers separated PH from non-PH patients with large effects. sPAP was 24 mmHg higher and TR velocity 0.9 m/s higher in PH (both p<0.0001), accompanied by RV remodeling (larger RV basal diameter) and impaired systolic function (lower TAPSE). These right-heart findings are biologically expected and closely mirror pathophysiology reviews and patient-level studies in ILD, where rising afterload leads to RV enlargement and contractile impairment; TAPSE and RV-PA coupling indices are repeatedly linked to disease severity and outcomes. Alhamad EH et al.(2020)^[8]

Categorical metrics reinforced this: RA area ≥18 cm² and RV dysfunction (FAC<35%) were 4-6× more frequent in PH, paralleling literature associating chamber enlargement and RV failure with adverse prognosis in PH-ILD and CLD-PH broadly. Rahaghi FF et al.(2022)^[9]

Functional impairment and gas-exchange abnormalities tracked with PH status. PH patients walked 68 m less on 6MWT and had lower resting SpO₂ and DLCO. Prior studies likewise link worse 6MWD and lower DLCO to the presence (and severity) of PH in ILD, and even to mortality risk-positioning these as pragmatic, clinic-side indicators to trigger PH evaluation. Results echo this gradient and are in line with observational and physiologic analyses showing DLCO and 6MWD as independent correlates of pulmonary hemodynamics and exertional desaturation. Shlobin OA et al.(2024)^[10]

We also observed clinical correlates consistent with the literature: PH patients tended to be older and have a longer ILD duration; LTOT use was >2× more common, reflecting greater hypoxemic burden. Male sex and ever-smoker status trended toward-but did not achieve-significance, a pattern variably reported across cohorts depending on ILD mix and severity adjustment. The borderline association with UIP pattern (p≈0.095) is directionally consistent with IPF’s higher PH risk yet may have been underpowered here once disease severity is partially captured by DLCO/6MWD. These observations collectively reinforce guideline messages: in ILD, a cluster of red flags-worsening exertional capacity, falling DLCO, increasing oxygen needs, and suggestive echo changes-should prompt systematic evaluation for PH and consideration of right-heart catheterization in appropriate candidates. Olsson KM et al.(2023)^[11]

Findings fit within the broader framework articulated by expert reviews and the 2022 ESC/ERS guidelines: echocardiography is the recommended first-line noninvasive screen (recognizing its limitations), with RHC as the diagnostic gold standard when confirmation will influence management. The strong separation of echo indices in data supports echocardiography’s real-world utility for triage and risk stratification in ILD clinics, while reminding clinicians that prevalence estimates are sensitive to population composition (subtype, severity) and that comprehensive assessment (including gas exchange, exercise testing, and imaging) improves detection. Guillén-Del-Castillo A et al.(2022)^[12]

This cross-sectional echocardiographic study demonstrated that pulmonary hypertension (PH) is a common comorbidity in patients with interstitial lung disease (ILD), affecting approximately one-third of the cohort. The prevalence varied across ILD subtypes, being highest in idiopathic pulmonary fibrosis and lowest in sarcoidosis. Echocardiographic indices such as elevated systolic pulmonary artery pressure, increased tricuspid regurgitation velocity, right ventricular enlargement, and reduced TAPSE were significantly associated with PH, highlighting the structural and functional impact on the right heart. Clinically, PH correlated with older age, longer disease duration, impaired exercise capacity, reduced diffusing capacity, and higher oxygen requirements. These findings reinforce the importance of systematic echocardiographic screening in ILD patients, as early recognition of PH may influence clinical management, prognostication, and timely referral for advanced therapies.

Limitations

The present study had certain limitations. First, the diagnosis of PH was based on echocardiographic estimation rather than right heart catheterization, which remains the gold standard, and this may have led to misclassification in some cases. Second, the cross-sectional design precluded assessment of temporal relationships between ILD progression and PH development. Third, the study was conducted in a single tertiary care center with a modest sample size, which may limit the generalizability of findings to wider populations. Fourth, potential confounders such as concomitant left heart disease or undetected chronic thromboembolic disease could not be completely excluded despite predefined exclusion criteria. Finally, longitudinal outcomes such as survival and treatment response were not evaluated, which would provide additional insights into the prognostic significance of PH in ILD.

1. Gupta RS, Koteci A, Morgan A, George PM, Quint JK. Incidence and prevalence of interstitial lung diseases worldwide: a systematic literature review. BMJ Open Respiratory Research. 2023 Jun 12;10(1).
2. Parikh R, Konstantinidis I, O'Sullivan DM, Farber HW. Pulmonary hypertension in patients with interstitial lung disease: a tool for early detection. Pulmonary Circulation. 2022 Oct;12(4):e12141.
3. DuBrock HM, Nathan SD, Reeve BB, Kolaitis NA, Mathai SC, Classi PM, Nelsen AC, Olayinka-Amao B, Norcross LN, Martin SA. Pulmonary hypertension due to interstitial lung disease or chronic obstructive pulmonary disease: a patient experience study of symptoms and their impact on quality of life. Pulmonary circulation. 2021 Apr;11(2):20458940211005641.
4. Wijsenbeek M, Suzuki A, Maher TM. Interstitial lung diseases. The Lancet. 2022 Sep 3;400(10354):769-86.
5. Waxman AB, Elia D, Adir Y, Humbert M, Harari S. Recent advances in the management of pulmonary hypertension with interstitial lung disease. European Respiratory Review. 2022 Jul 12;31(165).
6. Maher TM. Interstitial lung disease: a review. Jama. 2024 May 21;331(19):1655-65.
7. Nikkho SM, Richter MJ, Shen E, Abman SH, Antoniou K, Chung J, Fernandes P, Hassoun P, Lazarus HM, Olschewski H, Piccari L. Clinical significance of pulmonary hypertension in interstitial lung disease: a consensus statement from the Pulmonary Vascular Research Institute's innovative drug development initiative-Group 3 pulmonary hypertension. Pulmonary Circulation. 2022 Jul;12(3):e12127.
8. Alhamad EH, Cal JG, Alrajhi NN, Alharbi WM. Predictors of mortality in patients with interstitial lung disease-associated pulmonary hypertension. Journal of Clinical Medicine. 2020 Nov 26;9(12):3828.
9. Rahaghi FF, Kolaitis NA, Adegunsoye A, de Andrade JA, Flaherty KR, Lancaster LH, Lee JS, Levine DJ, Preston IR, Safdar Z, Saggar R. Screening strategies for pulmonary hypertension in patients with interstitial lung disease: a multidisciplinary Delphi study. Chest. 2022 Jul 1;162(1):145-55.
10. Shlobin OA, Adir Y, Barbera JA, Cottin V, Harari S, Jutant EM, Pepke-Zaba J, Ghofrani HA, Channick R. Pulmonary hypertension associated with lung diseases. European Respiratory Journal. 2024 Oct 31;64(4).
11. Olsson KM, Corte TJ, Kamp JC, Montani D, Nathan SD, Neubert L, Price LC, Kiely DG. Pulmonary hypertension associated with lung disease: new insights into pathomechanisms, diagnosis, and management. The Lancet Respiratory Medicine. 2023 Sep 1;11(9):820-35.
12. Guillén-Del-Castillo A, Meseguer ML, Fonollosa-Pla V, Giménez BS, Colunga-Argüelles D, Revilla-López E, Rubio-Rivas M, Ropero MJ, Argibay A, Barberá JA, Salas XP. Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension. Scientific reports. 2022 Mar 28;12(1):5289