Noninvasive diagnostic modalities and prediction models for detecting pulmonary hypertension associated with interstitial lung disease: a narrative review

Abstract

Pulmonary hypertension (PH) is highly prevalent in patients with interstitial lung disease (ILD) and is associated with increased morbidity and mortality. Widely available noninvasive screening tools are warranted to identify patients at risk for PH, especially severe PH, that could be managed at expert centres. This review summarises current evidence on noninvasive diagnostic modalities and prediction models for the timely detection of PH in patients with ILD. It critically evaluates these approaches and discusses future perspectives in the field. A comprehensive literature search was carried out in PubMed and Scopus, identifying 39 articles that fulfilled inclusion criteria. There is currently no single noninvasive test capable of accurately detecting and diagnosing PH in ILD patients. Estimated right ventricular pressure (RVSP) on Doppler echocardiography remains the single most predictive factor of PH, with other indirect echocardiographic markers increasing its diagnostic accuracy. However, RVSP can be difficult to estimate in patients due to suboptimal views from extensive lung disease. The majority of existing composite scores, including variables obtained from chest computed tomography, pulmonary function tests and cardiopulmonary exercise tests, were derived from retrospective studies, whilst lacking validation in external cohorts. Only two available scores, one based on a stepwise echocardiographic approach and the other on functional parameters, predicted the presence of PH with sufficient accuracy and used a validation cohort. Although several methodological limitations prohibit their generalisability, their use may help physicians to detect PH earlier. Further research on the potential of artificial intelligence may guide a more tailored approach, for timely PH diagnosis.

FIGURE 1

Echocardiographic markers used to detect pulmonary hypertension in a patient with idiopathic pulmonary fibrosis. a) Continuous-wave Doppler echocardiography on a modified right ventricular (RV) focused four-chamber view depicts an increased tricuspid valve regurgitation velocity of 3.3 m·s⁻¹. b) M-mode echocardiography applied on the RV free wall at the level of the tricuspid annulus reveals a reduced tricuspid annular plane systolic excursion. c) Right heart focused four-chamber view shows a severely dilated right atrium and a normal size of left atrium. d) Inferior vena cava distension (>21 mm) with diminished inspiratory collapsibility as depicted on a subcostal view.

FIGURE 2

Chest imaging signs suggestive of the presence of pulmonary hypertension in a patient with idiopathic pulmonary fibrosis. a) Chest radiograph showing a dilated main pulmonary artery with peripheral vascular “pruning” and cardiomegaly. b) High-resolution computed tomography depicting a diffuse fibrotic lung disease characterised by striking traction bronchiectasis, ground-glass lesions and fine reticulation. c) Computed tomographic pulmonary angiography (CTPA) showing a dilated pulmonary artery (PA) at the bifurcation level (37.3 mm) and an increased PA to ascending aorta diameter ratio of 1.05. d) CTPA also demonstrates an increased basal right ventricular diameter to left ventricular diameter ratio of 1.6.

FIGURE 3

Noninvasive independent predictors of pulmonary hypertension (PH) in patients with interstitial lung disease and the potential use of artificial intelligence to improve diagnostic accuracy. Variables in bold have been included in multiparametric models. Variables in italics are univariate predictors of PH. ^#: Transthoracic echocardiography (TTE) variables can be used to predict severe PH as proposed in the stepwise composite echocardiographic score by Bax et al. [7]. The other non-TTE variables in bold predict the presence of any PH. ^¶: Right ventricle (RV) and right atrium dilatation, RV hypertrophy, RV dysfunction (fractional area change ≤34%), early diastolic pulmonary regurgitation velocity ≥2.2 m·s⁻¹, left ventricle (LV) eccentricity index ≥1.1, interventricular septal flattening, dilated inferior vena cava [7]. AA: ascending aorta; AI: artificial intelligence; CTPA: computed pulmonary angiography; BNP: brain natriuretic peptide; D_LCO: diffusion capacity for carbon monoxide; FVC: forced vital capacity; 6MWD: 6-min walk distance; NT-proBNP: N terminal pro-brain natriuretic peptide; PA: pulmonary artery; P_ETCO2: end-tidal carbon dioxide pressure; RAD: right axis deviation; RBBB: right bundle branch block; S_pO2: peripheral oxygen saturation; TRV: tricuspid regurgitation velocity; Vʹ_E/Vʹ_CO2: ventilatory efficiency; Vʹ_O2peak: oxygen consumption at maximal exercise.