Pulmonary hypertension is a life‐limiting complication of interstitial lung disease (ILD‐PH). We investigated whether treatment with phosphodiesterase 5 inhibitors (PDE5i) in patients with ILD‐PH was associated with improved survival.

Pulmonary hypertension (PH) is a life-limiting complication of severe lung disease [1, 2]. We investigate whether patients treated with pulmonary vasodilators survive longer. Longitudinal haemodynamic, functional and treatment data from 184 consecutive incident group 3 PH patients with no connective tissue disease were prospectively collected from referral to death or censoring. Bayesian survival modelling assessed the association between treatment and survival. Patients were in subgroups 3.2 (ILD, 71%), 3.1 (COPD, 21%), 3.3 (CPFE, 5%), 3.4 (2%), 3.5 (1%) and 3.7 (1%). Median follow-up was 1.6 years (IQR: 0.7 – 2.7) and 147 patients (80%) died. Patients treated with phosphodiesterase 5 inhibitors (PDE5i) had similar baseline lung function parameters, higher mPAP (40.4 ± 9.5 vs. 36.1 ± 10.4, p=0.02), lower cardiac output (CO: 3.7 vs 4.3 L/min, p<0.001) and worse echocardiographic right heart function by TAPSE and FAC but survived longer than those not on PDE5i (median: 2.58 vs 1.42 years, p=0.0069). Patients treated/not-treated with endothelin receptor antagonists had similar baseline haemodynamics but no difference in survival. Benefits of PDE5i were confined to subgroup 3.2 and greatest in young females with normal baseline TAPSE. We suggest randomized controlled investigation of PDE5i in subgroup 3.2 patients is required to establish their long-term benefits.

BACKGROUND: Patients with interstitial lung disease (ILD) may develop pulmonary hypertension (PH), often disproportionate to the severity of the ILD. The right ventricular to left ventricular diameter (RV:LV) ratio measured at CT pulmonary angiogram (CTPA) has been shown to provide valuable information in patients with pulmonary arterial hypertension and to predict death or deterioration in acute pulmonary embolism. METHODS: Demographic characteristics, ILD subtype, echocardiography, and detailed CTPA measurements were collected in consecutive patients undergoing both CTPA and right heart catheterization at the Royal Brompton Hospital between 2005 and 2015. Fibrosis severity was formally scored according to CT criteria. The RV:LV ratio at CTPA was evaluated by using three different methods. Cox proportional hazards analysis was used to assess the relation of CTPA-derived parameters to predict death or lung transplantation. RESULTS: A total of 92 patients were included (64% male; mean age 65 +/- 11 years) with an FVC 57 +/- 20% predicted, corrected transfer factor of the lung for carbon monoxide 22 +/- 8% predicted, and corrected transfer coefficient of the lung for carbon monoxide 51 +/- 17% predicted. PH was confirmed at right heart catheterization in 78%. Of all the CTPA-derived measures, an RV:LV ratio >= 1.0 strongly predicted mortality or transplantation at univariate analysis (hazard ratio, 3.26; 95% CI, 1.49-7.13; P = .003), whereas invasive hemodynamic data did not. The RV:LV ratio remained an independent predictor at multivariate analysis (hazard ratio, 3.19; 95% CI, 1.44-7.10; P = .004), adjusting for an ILD diagnosis of idiopathic pulmonary fibrosis and CT imaging-derived ILD severity. CONCLUSIONS: An increased RV:LV ratio measured at CTPA provides a simple, noninvasive method of risk stratification in patients with suspected ILD-PH. This should prompt closer follow-up, more aggressive treatment, and consideration of lung transplantation.

European Respiratory Society (ERS) guidelines recommend the assessment of patients with interstitial lung disease (ILD) and severe pulmonary hypertension (PH), as defined by a mean pulmonary artery pressure (mPAP) ≥35 mmHg at right heart catheterisation (RHC). We developed and validated a stepwise echocardiographic score to detect severe PH using the tricuspid regurgitant velocity and right atrial pressure (right ventricular systolic pressure (RVSP)) and additional echocardiographic signs.Consecutive ILD patients with suspected PH underwent RHC between 2005 and 2015. Receiver operating curve analysis tested the ability of components of the score to predict mPAP ≥35 mmHg, and a score devised using a stepwise approach. The score was tested in a contemporaneous validation cohort. The score used “additional PH signs” where RVSP was unavailable, using a bootstrapping technique.Within the derivation cohort (n=210), a score ≥7 predicted severe PH with 89% sensitivity, 71% specificity, positive predictive value 68% and negative predictive value 90%, with similar performance in the validation cohort (n=61) (area under the curve (AUC) 84.8%versus83.1%, p=0.8). Although RVSP could be estimated in 92% of studies, reducing this to 60% maintained a fair accuracy (AUC 74.4%).This simple stepwise echocardiographic PH score can predict severe PH in patients with ILD.

Background: Pulmonary hypertension (PH) associated with interstitial lung disease (ILD) is associated with significant mortality. Aims: To describe the demographics and outcomes of patients with ILD referred to a National PH service. Methods: All patients with ILD referred for right heart catheterisation (RHC) between 2005 and 2015 were included. Patients were excluded if they had evidence of CTEPH or <10% severity of ILD at CT. The nearest echocardiogram, CT, BNP level and lung function to the RHC were used for comparison. Results: 310 patients were included (49% male). ILD diagnoses: IPF (72), CTD-ILD (108), sarcoid (56), CHP (26), NSIP (22) and ‘other ILD’ (26). At RHC 77% had a diagnosis of PH: mean PAP was 33 +/-11 mmHg, CO 4.2 +/- 1.3 L/min and PVR 6.2 +/- 4.1 Wood units. 42 % had severe PH (mean PAP≥ 35mmHg). Patients with PH had a higher BMI, were more likely to use LTOT but had no difference in ILD CT severity. They had lower FEV1 and TLCO but similar FVC. Median follow up time was 28 months. 74% died or had a transplant. ILD sub-type heavily influenced survival: CTD-ILD and sarcoid had the best survival; IPF the worst. However, patients with CTD-ILD and sarcoid were more likely to have received vasodilators. Conclusions: This well described cohort of patients demonstrates the poor prognosis of ILD associated PH and the importance of ILD diagnosis in refining risk stratification.

ABSTRACTBackground and objectiveIn interstitial lung disease (ILD), pulmonary hypertension (PH) is a major adverse prognostic determinant. Transthoracic echocardiography (TTE) is the most widely used tool when screening for PH, although discordance between TTE and right heart catheter (RHC) measured pulmonary haemodynamics is increasingly recognized. We evaluated the predictive utility of the updated European Society of Cardiology/European Respiratory Society (ESC/ERS) TTE screening recommendations against RHC testing in a large, well‐characterized ILD cohort.MethodsTwo hundred and sixty‐five consecutive patients with ILD and suspected PH underwent comprehensive assessment, including RHC, between 2006 and 2012. ESC/ERS recommended tricuspid regurgitation (TR) velocity thresholds for assigning high (>3.4 m/s), intermediate (2.9–3.4 m/s) and low (<2.8 m/s) probabilities of PH were evaluated against RHC testing.ResultsRHC testing confirmed PH in 86% of subjects with a peak TR velocity >3.4 m/s, and excluded PH in 60% of ILD subjects with a TR velocity <2.8 m/s. Thus, the ESC/ERS guidelines misclassified 40% of subjects as ‘low probability’ of PH, when PH was confirmed on subsequent RHC. Evaluating alternative TR velocity thresholds for assigning a low probability of PH did not significantly improve the ability of TR velocity to exclude a diagnosis of PH.ConclusionIn patients with ILD and suspected PH, currently recommended ESC/ERS TR velocity screening thresholds were associated with a high positive predictive value (86%) for confirming PH, but were of limited value in excluding PH, with 40% of patients misclassified as low probability when PH was confirmed at subsequent RHC.

Introduction: Main pulmonary artery diameter (MPAD) measured at CT has been evaluated in its ability to predict pulmonary hypertension (PH) associated with interstitial lung disease (PH-ILD). Little is known about longitudinal trends in MPAD or whether an increase in size predicts mortality. Methods: Demographics, ILD subtype and MPAD were measured in consecutive patients undergoing right heart catheterisation (RHC) for suspected PH-ILD. MPAD measured at the time of RHC were compared to MPAD within a 2-year period prior to or after RHC. CTs were anonymised and the reviewer blinded to clinical information. Outcome was evaluated for mortality using Cox proportional hazards. Results: 153 ILD patients were studied from 2005-2015. 39% had a CT prior to RHC, and 61% a CT after RHC for comparison to the CT performed at RHC. 79% had PH at RHC. MPAD decreased in size by ≥1mm in 27%, and increased by ≥1mm in 48%. Rate of change in MPAD predicted mortality (Hazard Ratio: 1.01, Confidence interval: 1.004-1.023, p= 0.005), which remained significant after adjustment for age, gender, ILD diagnosis, composite physiological index and baseline main pulmonary artery diameter. An increase in size of the MPAD ≥0.1mm/month was associated with an increased risk of mortality (HR: 2.0, CI: 1.3-3.0, p= 0.0007). Conclusion: MPAD measured at CT changes over time and the rate of change predicts mortality in PH-ILD.

Introduction: CT pulmonary angiography (CTPA) is important in the assessment of ILD patients with suspected PH (PH-ILD). We hypothesized that the assessment of right ventricular (RV) parameters would both predict PH and provide prognostic information. Methods: Demographics, ILD subtype and detailed RV measurements were collected in consecutive patients undergoing right heart catheterisation (RHC) and CTPA for suspected PH-ILD. CTPA were anonymised and the reviewer blinded to clinical information. Significant deviation of the ventricular septum or ‘septal bowing’ into the left ventricle was scored as present or absent. Results: From 2007-2015, 167 patients with suspected PH-ILD had a RHC and CTPA (0.8±1.5 months between tests), with 79% having PH at RHC. Patients with PH had a larger RV and a greater RV:LV ratio, and were more likely to have a bowed septum (p<0.001 for all). RV:LV ratio predicted PH (odds ratio (OR): 1.3, CI: 1.1-1.5, p<0.001) per unit increase. A RV:LV ratio ≥1.2 predicted PH (OR: 3.18, CI:1.6-6.4, p=0.006) with a sensitivity of 58%, specificity 70%, positive predictive value (PPV) 88% and negative predictive value (NPV) 29%. The presence of a bowed septum predicted PH (OR: 5.1, CI:2.2-14.3, p=0.004) with a sensitivity of 41%, specificity 88%, PPV 93% and NPV 28%. RV:LV ratio was associated with mortality (Hazard ratio (HR): 1.1, CI: 1.04-1.2, p<0.001) per unit increase. An RV:LV ratio ≥1.2 (HR: 1.96, CI: 1.3-2.8, p<0.001) and the presence of a bowed septum (HR: 1.6, CI: 1.1-2.4, p=0.008) predicted mortality. Conclusion: RV morphology on CTPA at the time of PH-ILD diagnosis provides predictive and prognostic information.

Introduction: Pulmonary hypertension is a malignant prognostic factor in ILD. Prognostic tools are required to help prioritise lung transplant allocation and have not been validated in PH-ILD. We hypothesised that the composite physiological index (CPI) would reliably predict prognosis in PH-ILD, as it reflects both the morphological extent of pulmonary fibrosis and pulmonary vascular disease. Methods: Demographics, ILD subtype, pulmonary function tests, and echocardiograms were collected in consecutive patients undergoing right heart catheterisation (RHC) for suspected PH-ILD. Predictors of prognosis were evaluated in their ability to predict mortality with Cox proportional hazard modelling. Results: 228 ILD patients underwent evaluation between 2005-2015, age 61±11 years, 52% were male, and 79% had PH at RHC. Mean pulmonary pressure (mPAP) in the 168 patients with PH was 37±9.3mmHg, mean pulmonary vascular resistance (PVR) 7.0±3.8 Wood units, mean CPI was 61±13. In the patients with PH-ILD, CPI predicted mortality (Hazard ratio (HR): 1.042, Confidence interval (CI): 1.03-1.06, p<0.001) per unit increase, this remained significant despite adjustment for age, mPAP and PVR at RHC. A threshold of 50 was strongly associated with an increased risk of mortality (HR: 4.12, CI: 2.13-7.91, p<0.001). Conclusion: The CPI strongly predicts mortality in ILD-PH.

Introduction: Cross sectional studies have highlighted the role of non-invasive markers in predicting interstitial lung disease (ILD) associated pulmonary hypertension (ILD-PH). Few studies have evaluated the role of longitudinal change in non-invasive variables, with repeat measurement of invasive pulmonary haemodynamics. Objectives: We hypothesized that non-invasive markers (KCO, echo parameters and main pulmonary artery size on CT) would correlate with invasive haemodynamics in ILD-PH. Methods: We performed a retrospective review of ILD and PH databases from the Royal Brompton Hospital. Identifying patients with ILD-PH who had baseline and follow up right heart catheters (RHC) (n=26). Diagnoses included Scleroderma ILD, MCTD-ILD, SLE-ILD, Sarcoid, IPF, FNSIP and chronic hypersensitivity pneumonitis. Data were compared using Wilcoxon signed rank test. Results: Of the 26 patients 6 developed PH over the study period, 11 patients mean pulmonary arterial pressure (mPAP) remained stable or increased and 9 patients had a fall in mPAP on repeat RHC. The median age in the group was 66 (28-77). Median interval between RHC 31.7 months (4-108). Patients who developed PH over the period had a median fall in KCO of -6.6% predicted (-1.3 to -32.5, p=0.03). CT main pulmonary artery measurements increased in all groups (p=0.0003). mPAP correlated with both KCO and RVSP (measurable in 87% of the study group at echo); (Spearman9s correlation coefficient) r= -0.36, p=0.01, and r=0.53, p=0.0007 respectively. Conclusion: In this preliminary cohort, non-invasive measurements reflect changes in invasive pulmonary haemodynamics in ILD-PH.