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Background Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pulmonary changes in these patients remains unclear. Research Question Do patients hospitalized with COVID-19 without evidence of architectural distortion on structural imaging exhibit longitudinal improvements in lung function measured by using 1H and 129Xe MRI between 6 and 52 weeks following hospitalization? Study Design and Methods Patients who were hospitalized with COVID-19 pneumonia underwent a pulmonary 1H and 129Xe MRI protocol at 6, 12, 25, and 51 weeks following hospital admission in a prospective cohort study between November 2020 and February 2022. The imaging protocol was as follows: 1H ultra-short echo time, contrast-enhanced lung perfusion, 129Xe ventilation, 129Xe diffusion-weighted, and 129Xe spectroscopic imaging of gas exchange. Results Nine patients were recruited (age 57 ± 14 [median ± interquartile range] years; six of nine patients were male). Patients underwent MRI at 6 (n = 9), 12 (n = 9), 25 (n = 6), and 51 (n = 8) weeks following hospital admission. Patients with signs of interstitial lung damage were excluded. At 6 weeks, patients exhibited impaired 129Xe gas transfer (RBC to membrane fraction), but lung microstructure was not increased (apparent diffusion coefficient and mean acinar airway dimensions). Minor ventilation abnormalities present in four patients were largely resolved in the 6- to 25-week period. At 12 weeks, all patients with lung perfusion data (n = 6) showed an increase in both pulmonary blood volume and flow compared with 6 weeks, although this was not statistically significant. At 12 weeks, significant improvements in 129Xe gas transfer were observed compared with 6-week examinations; however, 129Xe gas transfer remained abnormally low at weeks 12, 25, and 51. Interpretation 129Xe gas transfer was impaired up to 1 year following hospitalization in patients who were hospitalized with COVID-19 pneumonia, without evidence of architectural distortion on structural imaging, whereas lung ventilation was normal at 52 weeks.

Objectives:To evaluate the change in the number of CT pulmonary angiograms (CTPAs) performed and the change in the yield of acute pulmonary embolism (PE) on CTPA at a busy tertiary teaching hospital from 2016 to 2019.Methods:All CTPA examinations for both in-patients and emergency department patients performed at our busy tertiary teaching hospital between 1 January 2016 and 31 December 2019 were identified from the radiology information system. A natural language processing technique called phrase matching was employed to assign each of the examination reports a result of either positive, negative or equivocal for acute PE. This algorithm was validated on a sample of 200 reports.Results:The number of CTPAs performed increased 59% from 2016 to 2019. The overall yield of acute PE has remained steady averaging 15.9%, ranging from 15.0% to 17.2%.Conclusions:Over 3 years, there has been a significant increase in the demand for CTPA examinations. The yield of acute PE has remained steady indicating a justified increase in demand. The yield of acute PE on CTPA within our centre is higher than the Royal College of Radiologists’ suggested minimum of 15.4% which suggests the current guidelines used for the investigation of suspected acute PE within our centre are appropriate.Advances in knowledge:The guidelines and subsequent yield of acute PE on CTPA at our tertiary teaching hospital can be used as a reference standard for other similar institutes.

Objectives Computed tomography (CT) pulmonary angiography is widely used in patients with suspected pulmonary hypertension (PH). However, the diagnostic and prognostic significance remains unclear. The aim of this study was to (a) build a diagnostic CT model and (b) test its prognostic significance. Methods Consecutive patients with suspected PH undergoing routine CT pulmonary angiography and right heart catheterisation (RHC) were identified. Axial and reconstructed images were used to derive CT metrics. Multivariate regression analysis was performed in the derivation cohort to identify a diagnostic CT model to predict mPAP ≥ 25 mmHg (the existing ESC guideline definition of PH) and > 20 mmHg (the new threshold proposed at the 6th World Symposium on PH). In the validation cohort, sensitivity, specificity and compromise CT thresholds were identified with receiver operating characteristic (ROC) analysis. The prognostic value of the CT model was assessed using Kaplan-Meier analysis. Results Between 2012 and 2016, 491 patients were identified. In the derivation cohort (n = 247), a CT model was identified including pulmonary artery diameter, right ventricular outflow tract thickness, septal angle and left ventricular area. In the validation cohort (n = 244), the model was diagnostic, with an area under the ROC curve of 0.94/0.91 for mPAP ≥ 25/> 20 mmHg respectively. In the validation cohort, 93 patients died; mean follow-up was 42 months. The diagnostic thresholds for the CT model were prognostic, log rank, all p Discussion In suspected PH, a diagnostic CT model had diagnostic and prognostic utility. Key Points • Diagnostic CT models have high diagnostic accuracy in a tertiary referral population of with suspected PH. • Diagnostic CT models stratify patients by mortality in suspected PH.

IntroductionMicrovascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pathophysiological pulmonary changes during the post-acute period in these patients remains unclear.MethodsPatients who were hospitalised due to COVID-19 pneumonia underwent a pulmonary1H and129Xe MRI protocol at 6, 12, 25 and 51 weeks after hospital admission. The imaging protocol included: ultra-short echo time, dynamic contrast enhanced lung perfusion,129Xe lung ventilation,129Xe diffusion weighted and129Xe 3D spectroscopic imaging of gas exchange.Results9 patients were recruited and underwent MRI at 6 (n=9), 12 (n=9), 25 (n=6) and 51 (n=8) weeks after hospital admission. Patients with signs of interstitial lung damage at 3 months were excluded from this study. At 6 weeks after hospital admission, patients demonstrated impaired129Xe gas transfer (RBC:M) but normal lung microstructure (ADC, LmD). Minor ventilation abnormalities present in four patients were largely resolved in the 6–25 week period. At 12 week follow up, all patients with lung perfusion data available (n=6) showed an increase in both pulmonary blood volume and flow when compared to 6 weeks, though this was not statistically significant. At 12 week follow up, significant improvements in129Xe gas transfer were observed compared to 6-week examinations, however129Xe gas transfer remained abnormally low at weeks 12, 25 and 51. Changes in129Xe gas transfer correlated significantly with changes in pulmonary blood volume and TLCOZ-score.ConclusionsThis study demonstrates that multinuclear MRI is sensitive to functional pulmonary changes in the follow up of patients who were hospitalised with COVID-19. Impairment of xenon transfer may indicate damage to the pulmonary microcirculation.

The use of pulmonary MRI in a clinical setting has historically been limited. Whilst CT remains the gold-standard for structural lung imaging in many clinical indications, technical developments in ultrashort and zero echo time MRI techniques are beginning to help realise non-ionising structural imaging in certain lung disorders. In this invited review, we discuss a complementary technique – hyperpolarised (HP) gas MRI with inhaled3He and129Xe – a method for functional and microstructural imaging of the lung that has great potential as a clinical tool for early detection and improved understanding of pathophysiology in many lung diseases. HP gas MRI now has the potential to make an impact on clinical management by enabling safe, sensitive monitoring of disease progression and response to therapy. With reference to the significant evidence base gathered over the last two decades, we review HP gas MRI studies in patients with a range of pulmonary disorders, including COPD/emphysema, asthma, cystic fibrosis, and interstitial lung disease. We provide several examples of our experience in Sheffield of using these techniques in a diagnostic clinical setting in challenging adult and paediatric lung diseases.

This study aimed to determine the prognostic value of cardiovascular magnetic resonance (CMR) in patients with heart failure with preserved ejection fraction and associated pulmonary hypertension (pulmonary hypertension-HFpEF). Patients with pulmonary hypertension-HFpEF were recruited from the ASPIRE registry and underwent right heart catheterisation (RHC) and CMR. On RHC, the inclusion criteria was a mean pulmonary artery pressure (MPAP) ≥ 25 mmHg and pulmonary arterial wedge pressure > 15 mmHg and, on CMR, a left atrial volume > 41 ml/m2 with left ventricular ejection fraction > 50%. Cox regression was performed to evaluate CMR against all-cause mortality. In this study, 116 patients with pulmonary hypertension-HFpEF were identified. Over a mean follow-up period of 3 ± 2 years, 61 patients with pulmonary hypertension-HFpEF died (53%). In univariate regression, 11 variables demonstrated association to mortality: indexed right ventricular (RV) volumes and stroke volume, right ventricular ejection fraction (RVEF), indexed RV mass, septal angle, pulmonary artery systolic/diastolic area and its relative area change. In multivariate regression, only three variables were independently associated with mortality: RVEF (HR 0.64, P

Background Hyperpolarised gas magnetic resonance imaging (MRI) can be used to assess ventilation patterns. Previous studies have shown the image-derived metric of ventilation defect per cent (VDP) to correlate with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and FEV1 in asthma. Objectives The aim of this study was to explore the utility of hyperpolarised xenon-129 (129Xe) ventilation MRI in clinical care and examine its relationship with spirometry and other clinical metrics in people seen in a severe asthma service. Methods 26 people referred from a severe asthma clinic for MRI scanning were assessed by contemporaneous 129Xe MRI and spirometry. A subgroup of 18 patients also underwent reversibility testing with spirometry and MRI. Quantitative MRI measures of ventilation were calculated, VDP and the ventilation heterogeneity index (VHI), and compared to spirometry, Asthma Control Questionnaire 7 (ACQ7) and blood eosinophil count. Images were reviewed by a multidisciplinary team. Results VDP and VHI correlated with FEV1, FEV1/FVC and forced expiratory flow between 25% and 75% of FVC but not with ACQ7 or blood eosinophil count. Discordance of MRI imaging and symptoms and/or pulmonary function tests also occurred, prompting diagnostic re-evaluation in some cases. Conclusion Hyperpolarised gas MRI provides a complementary method of assessment in people with difficult to manage asthma in a clinical setting. When used as a tool supporting clinical care in a severe asthma service, occurrences of discordance between symptoms, spirometry and MRI scanning indicate how MRI scanning may add to a management pathway., This article demonstrates the feasibility of using 129Xe MRI in clinical practice. Discordance between symptoms, spirometry and MRI can support the use of further treatment or suggest coexisting breathing control issues or laryngeal disorders. https://bit.ly/3ky4oXP

Supplemental Digital Content is available in the text., Background: Approximately 25% of patients with pulmonary arterial hypertension (PAH) have been found to harbor rare mutations in disease-causing genes. To identify missing heritability in PAH, we integrated deep phenotyping with whole-genome sequencing data using Bayesian statistics. Methods: We analyzed 13 037 participants enrolled in the NBR study (NIHR BioResource—Rare Diseases), of which 1148 were recruited to the PAH domain. To test for genetic associations between genes and selected phenotypes of pulmonary hypertension, we used the Bayesian rare variant association method BeviMed. Results: Heterozygous, high impact, likely loss-of-function variants in the kinase insert domain receptor (KDR) gene were strongly associated with significantly reduced transfer coefficient for carbon monoxide (posterior probability=0.989) and older age at diagnosis (posterior probability=0.912). We also provide evidence for familial segregation of a rare nonsense KDR variant with these phenotypes. On computed tomographic imaging of the lungs, a range of parenchymal abnormalities were observed in the 5 patients harboring these predicted deleterious variants in KDR. Four additional PAH cases with rare likely loss-of-function variants in KDR were independently identified in the US PAH Biobank cohort with similar phenotypic characteristics. Conclusions: The Bayesian inference approach allowed us to independently validate KDR, which encodes for the VEGFR2 (vascular endothelial growth factor receptor 2), as a novel PAH candidate gene. Furthermore, this approach specifically associated high impact likely loss-of-function variants in the genetically constrained gene with distinct phenotypes. These findings provide evidence for KDR being a clinically actionable PAH gene and further support the central role of the vascular endothelium in the pathobiology of PAH.

Background and objective\ud There are limited data regarding patients with PAPVD with suspected and diagnosed PH.\ud \ud Methods\ud Patients with PAPVD presenting to a large PH referral centre during 2007–2017 were identified from the ASPIRE registry.\ud \ud Results\ud Ninety patients with PAPVD were identified; this was newly diagnosed at our unit in 71 patients (78%), despite 69% of these having previously undergone CT. Sixty‐seven percent had a single right superior and 23% a single left superior anomalous vein. Patients with an SV‐ASD had a significantly larger RV area, pulmonary artery and L‐R shunt and a higher % predicted DLCO (all P 3 WU. Seven of these patients had isolated PAPVD, five of whom (8% of those patients with PH) had anomalous drainage of a single pulmonary vein.\ud \ud Conclusion\ud Undiagnosed PAPVD with or without ASD may be present in patients with suspected PH; cross‐sectional imaging should therefore be specifically assessed whenever this diagnosis is considered. Radiological and physiological markers of L‐R shunt are higher in patients with an associated SV‐ASD. Although many patients with PAPVD and PH may have other potential causes of PH, a proportion of patients diagnosed with PAH have isolated PAPVD in the absence of other causative conditions.

Pulmonary hypertension (PH) is a challenging condition to diagnose and treat. Over the last two decades, there have been significant advances in therapeutic approaches and imaging technologies. Current guidelines emphasize the importance of cardiac catheterization; however, the increasing availability of non-invasive imaging has the potential to improve diagnostic rates, whilst providing additional information on patient phenotypes. Areas covered: This review discusses the role of imaging in the diagnosis, prognostic assessment and follow-up of patients with PH. Imaging methods, ranging from established investigations (chest radiography, echocardiography, nuclear medicine and computerized tomography (CT)), to emerging modalities (dual energy CT, magnetic resonance imaging (MRI), optical coherence tomography and positron emission tomography (PET)) are reviewed. The value and limitations of the clinical utility of these imaging modalities and their potential clinical application are reviewed. Expert commentary: Imaging plays a key role in the diagnosis and classification of pulmonary hypertension. It also provides valuable prognostic information and emerging evidence supports a role for serial assessments. The authors anticipate an increasing role for imaging in the pulmonary hypertension clinic. This will reduce the need for invasive investigations, whilst providing valuable insights that will improve our understanding of disease facilitate a more targeted approach to treatment.

Background: Computed tomography pulmonary angiography (CTPA) has been proposed to be diagnostic for pulmonary hypertension (PH) in multiple studies. However, the utility of the unenhanced CT measurements diagnosing PH has not been fully assessed. This study aimed to assess the diagnostic utility and reproducibility of cardiac and great vessel parameters on unenhanced computed tomography (CT) in suspected pulmonary hypertension (PH). Methods: In total, 42 patients with suspected PH who underwent unenhanced CT thorax and right heart catheterization (RHC) were included in the study. Three observers (a consultant radiologist, a specialist registrar in radiology, and a medical student) measured the parameters by using unenhanced CT. Diagnostic accuracy of the parameters was assessed by area under the receiver operating characteristic curve (AUC). Inter-observer variability between the consultant radiologist (primary observer) and the two secondary observers was determined by intra-class correlation analysis (ICC). Results: Overall, 35 patients were diagnosed with PH by RHC while 7 patients were not. Main pulmonary arterial (MPA) diameter was the strongest (AUC 0.79 to 0.87) and the most reproducible great vessel parameter. ICC comparing the MPA diameter measurement of the consultant radiologist to the specialist registrar’s and the medical student’s were 0.96 and 0.92, respectively. Right atrial area was the cardiac measurement with highest accuracy and reproducibility (AUC 0.76 to 0.79; ICC 0.980, 0.950) followed by tricuspid annulus diameter (AUC 0.76 to 0.79; ICC 0.790, 0.800). Conclusions: MPA diameter and right atrial areas showed high reproducibility. Diagnostic accuracies of these were within the range of acceptable to excellent, and might have clinical value. Tricuspid annular diameter was less reliable and less diagnostic and was therefore not a recommended diagnostic measurement.

Purpose Pulmonary hypertension (PH) is associated with a poor outcome in chronic obstructive pulmonary disease (COPD) and is diagnosed invasively. We aimed to assess the diagnostic accuracy and prognostic value of non-invasive cardiovascular magnetic resonance (CMR) models. Methods Patients with COPD and suspected PH, who underwent CMR and right heart catheter (RHC) were identified. Three candidate models were assessed: 1, CMR-RV model, based on right ventricular (RV) mass and interventricular septal angle; 2, CMR PA/RV includes RV mass, septal angle and pulmonary artery (PA) measurements; 3, the Alpha index, based on RV ejection fraction and PA size. Results Of 102 COPD patients, 87 had PH. The CMR-PA/RV model had the strongest diagnostic accuracy (sensitivity 92%, specificity 80%, positive predictive value 96% and negative predictive value 63%, AUC 0.93, p

Rationale: Prognostication is important when counseling patients and defining treatment strategies in pulmonary arterial hypertension (PAH).Objectives: To determine the value of magnetic resonance imaging (MRI) metrics for prediction of mortality in PAH.Methods: Consecutive patients with PAH undergoing MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) pulmonary hypertension registry.Measurements and Main Results: During the follow-up period of 42 (range, 17–142) months 576 patients were studied and 221 (38%) died. A derivation cohort (n = 288; 115 deaths) and validation cohort (n = 288; 106 deaths) were identified. We used multivariate Cox regression and found two independent MRI predictors of death (P

Background Previous studies have identified survival in systemic sclerosis (SSc)-associated pulmonary arterial hypertension (SSc-PAH) as being worse than in idiopathic pulmonary arterial hypertension (IPAH). We investigated differences between these conditions by comparing demographic, hemodynamic, and radiological characteristics and outcomes in a large cohort of incident patients. Methods Six hundred fifty-one patients diagnosed with IPAH or SSc-associated precapillary pulmonary hypertension were included. Patients with pulmonary disease or two or more risk factors for left heart disease were identified, leaving a primary analysis set of 375 subjects. Subgroup analysis using cardiac magnetic resonance (CMR) imaging was performed. Results Median survival was 7.8 years in IPAH and 3 years in SSc-PAH ( P P value for difference with IPAH = 0.095). The correlation between ventricular mass index assessed at CMR imaging and PVR was stronger in SSc-PAH. Conclusions The reasons for poorer outcomes in SSc-PAH are likely to be multifactorial, including but not limited to older age and reduced gas transfer.

PURPOSE: To assess the diagnostic accuracy of magnetic resonance imaging (MRI) perfusion against perfusion single photon emission tomography (SPECT) screening for chronic thromboembolic pulmonary hypertension (CTEPH). Ventilation/perfusion (V/Q) scintigraphy is recommended to screen for suspected CTEPH. It has previously been shown that 3D dynamic contrast-enhanced (DCE) lung perfusion MRI has a similar sensitivity for diagnosing CTEPH in comparison to planar perfusion scintigraphy; however, planar scintigraphy has now been largely replaced by SPECT, due to higher spatial resolution and sensitivity. MATERIALS AND METHODS: Consecutive patients with suspected CTEPH or unexplained pulmonary hypertension attending a referral center, who underwent lung DCE perfusion MRI at 1.5T, perfusion SPECT, and computed tomography pulmonary angiography (CTPA) within 14 days of right heart catheterization, from April 2013 to April 2014, were included. DCE-MR, SPECT, and CTPA were independently analyzed by two blinded radiologists. Disagreements were corrected by consensus. The gold standard reference for the diagnosis of chronic thromboemboli was based on a review of multimodality imaging and clinical findings. RESULTS: In all, 74 patients with suspected CTEPH underwent all three modalities. Forty-six were diagnosed with CTEPH (36) or chronic thromboembolic disease (CTED) (10). 3D DCE perfusion MRI correctly identified all patients (sensitivity of 100%), compared with a 97% sensitivity for SPECT. CONCLUSION: DCE lung perfusion MRI has increased sensitivity when compared with perfusion scintigraphy in screening for CTEPH. As MRI does not use ionizing radiation, it should be considered as a first-line imaging modality in suspected CTEPH. LEVEL OF EVIDENCE: 3

BackgroundApproximately 25% of patients with pulmonary arterial hypertension (PAH) have been found to harbor rare mutations in disease-causing genes. To identify missing heritability in PAH we integrated deep phenotyping with whole-genome sequencing data using Bayesian statistics.MethodsWe analyzed 13,037 participants enrolled in the NIHR BioResource - Rare Diseases (NBR) study, of which 1,148 were recruited to the PAH domain. To test for genetic associations between genes and selected phenotypes of pulmonary hypertension (PH), we used the Bayesian rare-variant association method BeviMed.ResultsHeterozygous, high impact, likely loss-of-function variants in the Kinase Insert Domain Receptor (KDR) gene were strongly associated with significantly reduced transfer coefficient for carbon monoxide (KCO, posterior probability (PP)=0.989) and older age at diagnosis (PP=0.912). We also provide evidence for familial segregation of a rare nonsense KDR variant with these phenotypes. On computed tomographic imaging of the lungs, a range of parenchymal abnormalities were observed in the five patients harboring these predicted deleterious variants in KDR. Four additional PAH cases with rare likely loss-of-function variants in KDR were independently identified in the US PAH Biobank cohort with similar phenotypic characteristics.ConclusionsThe Bayesian inference approach allowed us to independently validate KDR, which encodes for the Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), as a novel PAH candidate gene. Furthermore, this approach specifically associated high impact likely loss-of-function variants in the genetically constrained gene with distinct phenotypes. These findings provide evidence for KDR being a clinically actionable PAH gene and further support the central role of the vascular endothelium in the pathobiology of PAH.

Introduction Apparent diffusion coefficient (ADC) is a diffusion-weighted (DW) MRI measure of Brownian gas diffusion in the airspaces, where restrictions by tissue boundaries provide information about lung microstructure. The mean diffusive length scale (LmD) is another DW-MRI lung microstructure measurement calculated using a stretched exponential fit method. Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) quantifies various radiological parenchymal features based on histogram signature mapping techniques and is the most widely used quantitative CT image texture analysis software in interstitial lung disease (ILD). Aim To evaluate the ability of hyperpolarised 129-xenon (129Xe) DW-MRI and high resolution CT (HRCT) to distinguish between ILD subtypes. Methods A prospective, multicentre study of patients with ILD including drug induced ILD (DI-ILD), hypersensitivity pneumonitis (HP), idiopathic pulmonary fibrosis (IPF) and connective tissue disease ILD (CTD-ILD). Hyperpolarised 129Xe DW-MRI was performed on a 1.5 T scanner. The HRCT scan was performed within a year prior to the MRI scan. Quantitative CT analysis was performed using CALIPER. Semi-quantitative visual CT analysis was performed by two consultant chest radiologists using a scoring system (table 1). Results To date, 36 patients (8 DI-ILD, 8 HP, 15 IPF, 5 CTD-ILD) have undergone baseline 129Xe DW-MRI and CT analysis. There was a significant difference between the IPF and HP groups in ADC (p=0.031) and LmD (p=0.007). Quantitative CT analysis demonstrated a significant difference between the ILD subtypes in ground glass (GG) percent (p=0.031) and honeycombing (HC) percent (p=0.021) but not reticulation percent (p=0.14). The difference in GG% occurred between the IPF and HP groups (p=0.018), whereas the difference in HC% occurred between the IPF and DI-ILD groups (p=0.027). Semi-quantitative visual CT analysis showed a significant difference between the ILD subtypes in GG score (p=0.001), with the difference occurring between the IPF and HP groups (p Conclusions Our findings suggest significant differences in ADC, LmD, GG score and CALIPER GG% between IPF and HP patients. 129Xe DW-MRI and quantitative CT could potentially have a role in differentiating between these ILD subtypes.

Purpose: Right atrial (RA) area on echo and mean RA pressure (mRAP) at right heart catheterisation have prognostic value in PH and are included in ERS risk stratification tables. CT pulmonary angiography (CTPA) is commonly performed on patients with unexplained breathlessness and suspected PH. However, prognostic value of RA measured on CTPA in PH has not been studied. Aims: Investigate if CTPA RA area (CT RAx) correlates with mRAP. Secondarily, to assess if CTPA RAx can be used to risk stratify into low, medium & high-risk groups. Methods: 410 patients with PH, including 158 with pulmonary arterial hypertension (PAH), who underwent baseline CTPA and RHC within 90 days were identified from the ASPIRE registry. Pearson correlation between CT RAx and mRAP was assessed. Cohort was divided by ERS mRAP thresholds into low, medium & high risk ( 14 mmHg) and CT RAx difference between groups assessed with one-way ANOVA. Outcomes were assessed with Kaplan-Meier and Cox proportional hazards regression analysis. Results: During the follow up period, 89 patients died, 54 of whom had PAH. Mean survival was 4.7 for PH and 4.4 years for PAH. CT RAx correlated well with mRAP in both PH (r=0.482, p Conclusion: RA area measured on CTPA is a simple axial measurement which correlates with mRAP and predicts survival. Further studies to identify optimal CT prognostic thresholds is warranted.

Background: Computed tomography (CT) pulmonary angiography is widely used in patients with suspected pulmonary hypertension (PH). However, the diagnostic and prognostic significance remains unclear. The aim of this study was to (a) build a diagnostic CT model and (b) test its prognostic significance. Methods: Consecutive patients with suspected PH undergoing routine CT pulmonary angiography and right heart catheterization (RHC) were identified. Reconstructed images were used to derive CT metrics. Multivariate regression analysis was performed in the derivation cohort to identify a diagnostic CT model to predict mPAP ≥25mmHg and >20mmHg. In the validation cohort, sensitivity, specificity and compromise CT thresholds were identified with receiver operating characteristics (ROC) Results: Between 2012 and 2016, 491 patients were identified. In the derivation cohort, n=247, a CT model was identified including pulmonary artery diameter, right ventricular outflow tract thickness, septal angle and left ventricular area. In the validation cohort, n=244, the model was diagnostic, area under the ROC curve 0.94/0.91 for mPAP≥25/>20mmHg. In the validation cohort 93 patients died, mean follow-up of 42 months. The sensitive/specific/compromise thresholds for the CT model were prognostic, log rank 11.1/10.6/6.25 respectively, all p 20mmHg were not prognostic, p=0.09 and p=0.12, respectively. Conclusion: In suspected PH, a diagnostic CT model had diagnostic and prognostic utility. Conversely, the presence or absence of PH at RHC did not predict survival.

Introduction: Mutations in the bone morphogenetic receptor type 2 (BMPR2) gene are the commonest genetic cause of heritable pulmonary arterial hypertension (PAH). The aim of this study was to investigate thoracic computed tomography (CT) features in patients with idiopathic and heritable PAH and BMPR2 mutations. Methods: Patients with idiopathic or heritable PAH were selected; patients with mutations other than BMPR2 were excluded. CT features were assessed with observers blinded to the BMPR2 status. Independent t-test, Chi2 test, binary logistic regression and one-way ANCOVA were used to compare patients with and without BMPR2 mutation. Results: In a preliminary analysis of 111 patients with IPAH or HPAH from the Sheffield Pulmonary Vascular Disease Unit, 19 had a BMPR2 mutation. Mutation carriers were younger (p=0.009). No sex difference was identified (p=0.313). New peripheral lung blood vessels ‘neovascularity’ and enlarged bronchial arteries were observed in BMPR2 mutation carriers (p 0.05). After adjusting for age, sex, body surface area, WHO functional class, mPAP and PVR, a smaller left atrial area and smaller main pulmonary artery diameter were associated with a BMPR2 mutation. Conclusion: In this preliminary analysis of the UK National IPAH cohort, we have observed that BMPR2 carriers had smaller pulmonary arteries and smaller left atria. Whether this reflects differences in RV afterload and left ventricle preload requires further investigation.

There are limited published data defining survival and treatment response in patients with mild lung disease and/or reduced gas transfer who fulfil diagnostic criteria for idiopathic pulmonary arterial hypertension (IPAH). Patients diagnosed with IPAH between 2001 and 2019 were identified in the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) registry. Using prespecified criteria based on computed tomography (CT) imaging and spirometry, patients with a diagnosis of IPAH and no lung disease were termed IPAHno-LD (n=303), and those with minor/mild emphysema or fibrosis were described as IPAHmild-LD (n=190). Survival was significantly better in IPAHno-LD than in IPAHmild-LD (1- and 5-year survival 95% and 70% versus 78% and 22%, respectively; p, Patients with IPAH who have mild parenchymal lung disease have significantly worse outcomes, in terms of survival and treatment response, when compared to patients with IPAH who do not have evidence of parenchymal lung disease http://bit.ly/3agkYn0

Purpose To derive and test multiparametric cardiac MRI models for the diagnosis of pulmonary hypertension (PH). Materials and Methods Images and patient data from consecutive patients suspected of having PH who underwent cardiac MRI and right-sided heart catheterization (RHC) between 2012 and 2016 were retrospectively reviewed. Of 2437 MR images identified, 603 fit the inclusion criteria. The mean patient age was 61 years (range, 18-88 years; mean age of women, 60 years [range, 18-84 years]; mean age of men, 62 years [range, 22-88 years]). In the first 300 patients (derivation cohort), cardiac MRI metrics that showed correlation with mean pulmonary arterial pressure (mPAP) were used to create a regression algorithm. The performance of the model was assessed in the 303-patient validation cohort by using receiver operating characteristic (ROC) and χ

Purpose To assess interventricular septal (IVS) angle in the identification of combined pre- and postcapillary pulmonary hypertension (Cpc-PH) in patients with pulmonary hypertension (PH) due to left-sided heart disease. Materials and Methods In this retrospective study, consecutive, incident patients suspected of having PH underwent same-day right-sided heart catheterization (RHC) and MRI at a PH referral center between April 2012 and April 2017. The diagnostic accuracy of the IVS angle to identify Cpc-PH in patients with pulmonary arterial wedge pressure (PAWP) greater than 15 mmHg was assessed by using receiver operator characteristic curves, sensitivity, specificity, and negative and positive predictive values. IVS angle also was assessed as a predictor of all-cause mortality by using Cox uni- and multivariable proportional hazards regression. Results A total of 708 patients underwent same-day MRI and RHC, and 171 patients had PAWP greater than 15 mmHg. Mean age was 70 years (range, 21-90 years) (women: mean age, 69 years; range, 21-88 years) (men: mean age, 71 years; range, 43-90 years). Systolic IVS angle correlated with diastolic pulmonary gradient (DPG) (r = 0.739, P.001). Receiver operating characteristic curve analysis showed septal angle enabled identification of Cpc-PH (DPG ≥ 7), with an area under the receiver operating characteristic curve of 0.911 (P.001). A 160° threshold, derived from the first half of patients with raised PAWP, enabled identification of a DPG of at least 7 mmHg with 67% sensitivity and 93% specificity (P.001) in the second cohort of patients with raised PAWP. IVS angle was predictive of all-cause mortality (standardized univariable hazard ratio, 1.615; P.01). Conclusion The systolic interventricular septal angle is elevated in patients with combined pre- and postcapillary pulmonary hypertension and enables one to predict those patients who have PH due to left-sided heart disease who have an increased risk of death. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Purpose It is postulated that ILD causes PA dilatation independent of the presence of pulmonary hypertension (PH), so the use of PA size to screen for PH is not recommended. The aims of this study were to investigate the association of PA size with the presence and severity of ILD and to assess the diagnostic accuracy of PA size for detecting PH. Methods Incident patients referred to a tertiary PH centre underwent baseline thoracic computed tomography (CT), magnetic resonance imaging (MRI) and right heart catheterisation (RHC). Pulmonary artery diameter was measured on CT pulmonary angiography and pulmonary arterial areas on MRI. A thoracic radiologist scored the severity of ILD on CT from 0–4, 0=absent, 1=1–25%, 2=26–50%, 3=51–75%, and 4=76–100% extent of involvement. Receiver operating characteristic analysis and linear regression were employed to assess diagnostic accuracy and independent associations of PA size. Results 110 had suspected PH due to ILD (age 65 years (SD 13), M:F 37:73) and 379 had suspected PH without ILD (age 64 years (SD 13), M:F 161:218). CT derived main PA diameter was accurate for detection of PH in patients both with and without ILD - AUC 0.873, p=

Summary Background With increasing survival of patients with more severe forms of congenital diaphragmatic hernia (CDH) and risk of long-term respiratory morbidity, studies on lung morphology are needed. We used hyperpolarised 3He MRI and anatomical 1H MRI in a cohort of young adult CDH patients to image regional lung ventilation and microstructure, focusing on morphological and micro-structural (alveolar) abnormalities. Methods Nine patients with left-sided CDH, born 1975–1993, were studied. Regional ventilation was imaged with hyperpolarised 3He MRI, and the 3He apparent diffusion coefficient (ADC) was computed separately for the ipsilateral and contralateral lungs. 1H MRI was used to image lung anatomy, total lung volume and motion during free-breathing. Results 3He MRI showed ventilation abnormalities in six patients, ranging from a single ipsilateral ventilation defect (3 patients) to multiple ventilation defects in both lungs (one patient treated with extra corporeal membrane oxygenation). In eight patients, 3He ADC values for the ipsilateral lung were significantly higher than those for the contralateral lung. Conclusions Functional and micro-structural changes persist into adulthood in most CDH patients. Ipsilateral elevated 3He ADC values are consistent with enlargement of mean dimensions of the confining lung micro-structure at the alveolar level. Pediatr Pulmonol. 2015; 9999:1–10. © 2015 Wiley Periodicals, Inc.

Right ventricular (RV) function is a strong predictor of outcome in cardiovascular diseases. Two components of RV function, longitudinal and transverse motion, have been investigated in pulmonary hypertension (PH). However, their individual clinical significance remains uncertain. The aim of this study was to determine the factors associated with transverse and longitudinal RV motion in patients with PH. In 149 treatment-naive patients with PH and 16 patients with suspected PH found to have mean pulmonary arterial pressure of

Introduction Pulmonary hypertension (PH) is severe cardiorespiratory condition associated with poor prognosis with diagnosis reliant on invasive right heart catheterization (RHC). Several measurements on computed tomography (CT) have been shown to have diagnostic value in PH, however few studies have attempted to identify the added value of combining CT metrics for the diagnosis of PH. The aim of this study is to develop a composite diagnostic CT model for patients with suspected PH. Methods Patients with suspected PH who underwent CT and RHC were identified. Standard axial and reconstructed images were used to derive CT metrics of cardiac and pulmonary vasculature anatomy. A derivation and validation cohort were randomly constructed to derive and test a binary logistic regression model of PH. Receiver operating characteristic (ROC) analysis assessed the diagnostic value of the model and individual metrics. Results 491 patients were identified (derivation cohort n=247 and validation n=244). Main pulmonary arterial (MPA) diameter, right ventricular outflow tract (RVOT) thickness, right ventricular muscle area and interventricular septal (IVS) angle variables correlated strongest to mean pulmonary arterial pressure, r=0.458 (p Conclusion A multivariate diagnostic model derived from axial CT images is accurate in suspected PH. The identified highly sensitive and specific thresholds may help in both patient screening and in selection for referral to specialist centres.

Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is potentially curable by pulmonary endarterectomy (PEA). Despite this a significant proportion of patients offered PEA decline surgery. Objective To compare long term survival and prognostic indicators in patients with technically operable CTEPH who underwent PEA and those who declined surgery. Methods Data were collected for consecutive, treatment-naive patients diagnosed with CTEPH between 2001 and 2014 identified from the ASPIRE-pulmonary-hypertension-registry. Results Of 588 patients with CTEPH, 368 patients were offered surgery. Seventy six percent (n=281) underwent PEA, 20% (n=72) declined surgery and 4% (n=15) were planned to undergo surgery. Five year survival was superior in patients undergoing PEA at 83% compared to patients who declined surgery at 56% (p=0.001, log-rank test). In patients who were offered surgery, mixed venous oxygen saturation (SvO2) (p=0.003), gas transfer (DLco) (p=0.042), history of coronary artery disease (p=0.031) and patient choice (declining surgery) (p Conclusion In a cohort of consecutive patients with CTEPH the long-term survival of patients undergoing PEA is excellent and superior to patients declining surgery and strongly favours surgical intervention in eligible patients. More work is required to understand factors influencing decision making in CTEPH and to ensure that patients are counselled and supported to make informed decisions.

Patients with left heart disease commonly develop pulmonary hypertension (PH), and some subsequently develop pre-capillary vascular remodelling. This combined pre and post capillary pulmonary hypertension (Cpc-PH) is defined as mean pulmonary artery pressure (mPAP) ≥25 mmHg, pulmonary arterial wedge pressure (PAWP) >15 mmHg and diastolic pulmonary gradient (DPG) of ≥7. Patients with Cpc-PH, have a worse outcome and targeted pulmonary vascular therapies may be useful. The aim of this study was to assess MRI measured septal angle in the assessment of Cpc-PH. Methods Consecutive, incident suspected PH patients who underwent MRI at a pulmonary hypertension referral centre from April 2012 to October 2015 were assessed. Patients with PAWP >15 mmHg, with right heart catheter and MRI on the same day were included. The diagnostic accuracy of septal angle to identify Cpc-PH was assessed. Results 2437 patients underwent MRI, 1272 were incident and 227 patients had PAWP >15 mmHg. 163 had MRI and right heart catheter on the same date. The average age was 70 (sd 11), 64% were female. Systolic interventricular septal angle correlated with DPG (r=0.735, p Conclusion Interventricular septal angle on MRI can non-invasively predict the presence of an elevated diastolic pressure gradient in patients with left heart disease.

Background Identification of patients with left heart disease (LHD) as the cause of pulmonary hypertension is challenging, developing a tool that can identify these patients would reduce unnecessary referral for investigation at specialist centres and may reduce the burden of invasive investigations. The aim was to investigate the capability of computed tomography (CT)-derived metrics for the diagnosis LHD in a cohort of patients with suspected pulmonary hypertension. Methods Patients with suspected pulmonary hypertension who underwent CT and RHC were identified. Derivation and validation cohorts were randomly constructed to derive and test a binary logistic regression model. All image analysis took place on PACS system blinded to patient’s cardiac catheter data and diagnosis. CT measurements of the cardiac chambers and vessels were taken. LHD was defined by increased pulmonary arterial wedge pressure (PAWP) ≥15 mmHg. A second threshold of 18 mmHg defined more advanced LHD. Backward binary logistic regression in a derivation cohort identified a model for predicting Group 2 PH. This model was tested in the validation cohort and compared to individual CT derived variables using receiver operating characteristic curve analysis and chi-square. Results The CT scans were from 66 different centres and 446 patients were identified, derivation cohort (n=235) and validation cohort (n=211). Left atrial area was found to be most significant individual predictor of elevated PAWP, area under curve (AUC) 0.86, p Conclusions CT derived left atrial area is a specific predictor of LHD in suspected pulmonary hypertension. Composite models did not increase diagnostic value. Left atrial area on CT may be a useful tool for diagnosing PH-LHD and may reduce unnecessary referrals to specialist PH centres and reduce the number of invasive investigations.

We evaluated the prevalence and prognostic value of CT-pulmonary angiographic (CTPA) measures in 292 treatment naive patients with pulmonary arterial hypertension (PAH). Pulmonary artery calcification (13%) and thrombus (10%) were exclusively seen in PAH-congenital heart disease. Oesophageal dilation (46%) was most frequent in PAH-systemic sclerosis. Ground glass opacification (GGO) (41%), pericardial effusion (38%), lymphadenopathy (19%) and pleural effusion (11%) were common. On multivariate analysis, inferior vena caval area, the presence of pleural effusion and septal lines predicted outcome. In PAH, CTPA provides diagnostic and prognostic information. In addition, the presence of GGO on a CT performed for unexplained breathlessness should alert the physician to the possibility of PAH.

Objectives The aim of this study was to develop a composite numerical model based on parameters from cardiac magnetic resonance (CMR) imaging for noninvasive estimation of the key hemodynamic measurements made at right heart catheterization (RHC). Background Diagnosis and assessment of disease severity in patients with pulmonary hypertension is reliant on hemodynamic measurements at RHC. A robust noninvasive approach that can estimate key RHC measurements is desirable. Methods A derivation cohort of 64 successive, unselected, treatment naive patients with suspected pulmonary hypertension from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) Registry, underwent RHC and CMR within 12 h. Predicted mean pulmonary arterial pressure (mPAP) was derived using multivariate regression analysis of CMR measurements. The model was tested in an independent prospective validation cohort of 64 patients with suspected pulmonary hypertension. Surrogate measures of pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were estimated by left atrial volumetry and pulmonary arterial phase contrast imaging, respectively. Noninvasive pulmonary vascular resistance (PVR) was calculated from the CMR-derived measurements, defined as: (CMR-predicted mPAP – CMR-predicted PCWP)/CMR phase contrast CO. Results The following composite statistical model of mPAP was derived: CMR-predicted mPAP = –4.6 + (interventricular septal angle × 0.23) + (ventricular mass index × 16.3). In the validation cohort a strong correlation between mPAP and MR estimated mPAP was demonstrated (R2 = 0.67). For detection of the presence of pulmonary hypertension the area under the receiver-operating characteristic (ROC) curve was 0.96 (0.92 to 1.00; p Conclusions CMR imaging can accurately estimate mean pulmonary artery pressure in patients with suspected pulmonary hypertension and calculate PVR by estimating all major pulmonary hemodynamic metrics measured at RHC.

Purpose To assess the diagnostic accuracy of magnetic resonance imaging (MRI) perfusion against perfusion single photon emission tomography (SPECT) screening for chronic thromboembolic pulmonary hypertension (CTEPH). Ventilation/perfusion (V/Q) scintigraphy is recommended to screen for suspected CTEPH. It has previously been shown that 3D dynamic contrast‐enhanced (DCE) lung perfusion MRI has a similar sensitivity for diagnosing CTEPH in comparison to planar perfusion scintigraphy; however, planar scintigraphy has now been largely replaced by SPECT, due to higher spatial resolution and sensitivity. Materials and Methods Consecutive patients with suspected CTEPH or unexplained pulmonary hypertension attending a referral center, who underwent lung DCE perfusion MRI at 1.5T, perfusion SPECT, and computed tomography pulmonary angiography (CTPA) within 14 days of right heart catheterization, from April 2013 to April 2014, were included. DCE‐MR, SPECT, and CTPA were independently analyzed by two blinded radiologists. Disagreements were corrected by consensus. The gold standard reference for the diagnosis of chronic thromboemboli was based on a review of multimodality imaging and clinical findings. Results In all, 74 patients with suspected CTEPH underwent all three modalities. Forty‐six were diagnosed with CTEPH (36) or chronic thromboembolic disease (CTED) (10). 3D DCE perfusion MRI correctly identified all patients (sensitivity of 100%), compared with a 97% sensitivity for SPECT. Conclusion DCE lung perfusion MRI has increased sensitivity when compared with perfusion scintigraphy in screening for CTEPH. As MRI does not use ionizing radiation, it should be considered as a first‐line imaging modality in suspected CTEPH. Level of Evidence: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1693–1697.

Introduction: Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a life shortening condition that may be cured by pulmonary endarterectomy.However, patients may not undergo surgery due to disease distribution, comorbidities or patient choice. Aims and objectives: To compare long term survival of patients with CTEPH undergoing pulmonary endarterectomy (CTEPH-surgical-operated), surgically accessible disease not undergoing endarterectomy due to comorbidities/patient choice (CTEPH-surgical-not-operated) and surgically inaccessible disease (CTEPH-non-surgical). Methods: Data was retrieved from the Sheffield ASPIRE Registry for consecutive, treatment-naive patients with CTEPH diagnosed between 2001 and 2015. Results: 613 patients, mean age(±standard deviation), 62±15 years, mean pulmonary arterial pressure 46±11mmHg and pulmonary vascular resistance 622±348dynes were identified and followed for 4.5±3.5 years. 5 year survival was significantly (p Conclusions: For patients with operable CTEPH pulmonary endarterectomy is associated with an excellent long term survival as previously reported. In addition we have shown that long-term survival of patients with surgical disease who decline surgery is significantly better than previously reported.

Introduction: Survival in SSc-PAH is worse than IPAH despite milder haemodynamics. Methods: 651 patients fulfilling criteria for PAH were identified. Patients with ≥2 cardiovascular risk factors or evidence of >limited lung disease were excluded leaving 183 IPAH and 192 SSc-PAH patients. MRI and CT assessment was performed in a subset. Results: Compared with IPAH, SSc-PAH patients were older with milder haemodynamics but lower exercise capacity and DLco and poorer survival (5-yr 35% v 65%, p

CTEPH is a potentially curable cause of pulmonary hypertension. V/Q scintigraphy is recommended for screening but requires exposure to ionising radiation. 3D lung perfusion MRI has been shown to have similar sensitivity for diagnosing CTEPH, compared to planar perfusion scintigraphy, however planar imaging has now been largely replaced by SPECT. Our aim was to assess the diagnostic accuracy of MRI perfusion against perfusion SPECT in CTEPH screening. METHODS & RESULTS: One year of consecutive suspected CTEPH patients attending a PH centre with perfusion MRI, perfusion SPECT and CTPA within 14 days were included. MR, SPECT and CTPA were independently analysed by two blinded radiologists. Disagreements were corrected by consensus. 74 suspected CTEPH patients attended for perfusion MRI, SPECT and CTPA. 46 were diagnosed with CTEPH/CTED at the PH MDT. 3D MRI lung perfusion correctly identified all patients, (100% sensitivity), compared to 96% sensitivity for SPECT. There was 1 indeterminate SPECT case and 2 indeterminate MRI cases. DISCUSSION: Lung perfusion MRI has increased sensitivity compared with perfusion scintigraphy in CTEPH. As MRI does not use ionising radiation and is an established part of the PH patient pathway it is a worthy screening test for suspected CTEPH.

Previous studies have identified survival in systemic sclerosis (SSc)-associated pulmonary arterial hypertension (SSc-PAH) as being worse than in idiopathic pulmonary arterial hypertension (IPAH). We investigated differences between these conditions by comparing demographic, hemodynamic, and radiological characteristics and outcomes in a large cohort of incident patients.Six hundred fifty-one patients diagnosed with IPAH or SSc-associated precapillary pulmonary hypertension were included. Patients with pulmonary disease or two or more risk factors for left heart disease were identified, leaving a primary analysis set of 375 subjects. Subgroup analysis using cardiac magnetic resonance (CMR) imaging was performed.Median survival was 7.8 years in IPAH and 3 years in SSc-PAH (P .001). Patients with SSc-PAH were older with less severe hemodynamics but lower gas transfer (diffusing capacity for carbon monoxide [Dlco]). Independent prognostic factors were age, SSc, Dlco, pulmonary artery saturation, and stroke volume. After excluding patients with normal or only mildly elevated resistance, there was no difference in the relationship between pulmonary vascular resistance (PVR) and compliance in IPAH and SSc-PAH. The relationship between mean pulmonary arterial pressure (mPAP) and systolic pulmonary arterial pressure (sPAP) in IPAH was identical to that previously reported (mPAP = 0.61 sPAP + 2 mm Hg). The relationship in SSc-PAH was similar: mPAP = 0.58 sPAP + 2 mm Hg (P value for difference with IPAH = 0.095). The correlation between ventricular mass index assessed at CMR imaging and PVR was stronger in SSc-PAH.The reasons for poorer outcomes in SSc-PAH are likely to be multifactorial, including but not limited to older age and reduced gas transfer.