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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 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.

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

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.

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 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=

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.

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.

The aim of this study was to assess the effect on neonatal thyroid function of iodinated contrast media administered for CT pulmonary angiography (CTPA) in babies whose mothers were investigated for suspected pulmonary embolism during pregnancy.Retrospective review of 115 pregnant patients investigated for suspected pulmonary embolism. The patient cohort consisted of two groups: Group A consisted of 73 pregnant females who received iodinated contrast agent for CTPA, and Group B (control group) consisted of 42 pregnant females who were investigated by perfusion imaging only. The results of the neonatal thyroid function tests for the babies of the mothers in Groups A and B were compared.All of the neonatal thyroid function tests for both groups were normal with no statistical difference between the two groups.No adverse effect on thyroid function was demonstrated in neonates exposed to in utero iodinated contrast media. However, as our study involves a small patient group, the results should be interpreted with caution.

A 73-year-old retired miner, with 36 years ‘at the coal face’, presented with a 5-year history of exertional dyspnoea on climbing steep inclines. His medical history was limited to quiescent chronic lymphocytic lymphoma, for which he required no chemotherapy or radiotherapy and had annual haematology follow-up. He was a smoker, with a 15 pack-year history, and took no regular medications. The patient had a widely split second heart sound, with accentuation of the pulmonary component, and bilateral intercostal bruits. Echocardiography demonstrated normal left sided chambers, moderate mitral and tricuspid regurgitation, and a raised estimated systolic pulmonary artery pressure of 80 mm Hg. Pulmonary function tests showed an obstructive pattern (FEV1 1.91 L (70% predicted), FVC 3.62 L (101%), FEV1/FVC ratio 53%), with a mildly reduced diffusion capacity (transfer coefficient (KCO) 0.86 mmol/min/KPa/L, 70% predicted). On the incremental shuttle walking test, his oxygen saturations dropped from …

We thank Marloes et al for their comments on our recently published article and their interest in pulmonary artery (PA) size as a potential prognostic marker and also their comments regarding adjusting the measurement for body surface area (BSA).1 First, we do recognise the diagnostic value of PA size and PA to aortic (PA:Ao) ratio in selected subgroups of patients, and we have previously shown that a PA:Ao ratio ≥1 in patients with systemic sclerosis and suspected pulmonary arterial hypertension (PAH) is highly suggestive of …

Background Previous studies have demonstrated survival in systemic sclerosis (SSc)-associated pulmonary arterial hypertension (SSc-PAH) to be worse than in idiopathic pulmonary arterial hypertension (IPAH). Possible explanations include age, differences in the underlying pulmonary vasculopathy and the ability of the right ventricle to compensate for the increased afterload.1 We investigated differences between these conditions by comparing demographic, haemodynamic and cardiac magnetic resonance imaging (MRI) characteristics and outcomes in a large cohort of incident, treatment-naive patients. Methods 183 patients with IPAH and 192 patients with SSc-PAH were identified from departmental databases including the ASPIRE registry.2 Sub-group analysis in 83 patients who had undergone cardiac MRI within 14 days of right heart catheterisation was performed. Results Median survival in IPAH was 7.8 years and in SSc-PAH was 3 years (p Conclusion The reasons for poorer outcomes in SSc-PAH are likely to be multifactorial including, but not limited to, older age, increased pulmonary arterial stiffness and reduced gas transfer. References Condliffe R, Howard LS. Connective tissue disease-associated pulmonary arterial hypertension. F1000 Prime Rep. 2015;7:06. Hurdman J, Condliffe R, Elliot CA, et al. ASPIRE registry: assessing the spectrum of pulmonary hypertension Identified at a REferral centre. Eur Respir J. 2012;39(4):945–955.

Dynamic contrast-enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for detecting reduced CI (FWHM area under the curve [AUC] at receiver operating characteristic analysis = 0.91 and PTT AUC = 0.92, respectively) and for detecting elevated PVRI (FWHM AUC = 0.88 and PTT AUC = 0.84, respectively). During the follow-up period, 25 patients died. Patients with longer measurements of FWHM (P = 0.0014) and PTT (P = 0.004) were associated with poor outcome at Kaplan-Meier analysis, and both parameters were strong predictors of adverse outcome from Cox proportional hazards analysis (P = 0.013 and 0.010, respectively). At bivariate analysis, DCE measurements predicted mortality independent of age, gender, and World Health Organization functional class; however, invasive hemodynamic indexes CI, PVRI, and DCE measurements were not independent of one another. In conclusion, DCE-MR transit times predict mortality in patients with PAH and are closely associated with clinical gold standards CI and PVRI.

Background— There are limited data on the prognostic value of cardiovascular magnetic resonance measurements in idiopathic pulmonary arterial hypertension, with no studies investigating the impact of correction of cardiovascular magnetic resonance indices for age and sex on prognostic value. Methods and Results— Consecutive patients with idiopathic pulmonary arterial hypertension underwent cardiovascular magnetic resonance imaging at 1.5T. Steady-state free precession cardiac volumes and mass measurements were corrected for age, sex, and body surface area according to reference data and prognostic significance assessed. A total of 80 patients with idiopathic pulmonary arterial hypertension were identified, and 23 patients died during the mean follow-up of 32±14 months. Corrected for age, sex, and body surface area, right ventricular end-systolic volume ( P =0.004) strongly predicted mortality, independent of World Health Organization functional class, mean right atrial pressure, cardiac index, and mixed venous oxygen saturations. Conclusions— Consideration should be given to correcting cardiovascular magnetic resonance measures for age, sex, and body surface area, particularly given the changing demographics of patients with idiopathic pulmonary arterial hypertension. Corrected right ventricular end-systolic volume is a strong prognostic marker in idiopathic pulmonary arterial hypertension, independent of invasively derived measurements, mean right atrial pressure cardiac index, and mixed venous oxygen saturations.

The phenotype and outcome of severe pulmonary hypertension in chronic obstructive pulmonary disease (COPD) is described in small numbers, and predictors of survival are unknown. Data was retrieved for 101 consecutive, treatment-naive cases of pulmonary hypertension in COPD. Mean ± SD follow-up was 2.3 ± 1.9 years. 59 patients with COPD and severe pulmonary hypertension, defined by catheter mean pulmonary artery pressure ≥40 mmHg, had significantly lower carbon monoxide diffusion, less severe airflow obstruction but not significantly different emphysema scores on computed tomography compared to 42 patients with mild-moderate pulmonary hypertension. 1- and 3-year survival for severe pulmonary hypertension, at 70% and 33%, respectively, was inferior to 83% and 55%, respectively, for mild-moderate pulmonary hypertension. Mixed venous oxygen saturation, carbon monoxide diffusion, World Health Organization functional class and age, but not severity of airflow obstruction, were independent predictors of outcome. Compassionate treatment with targeted therapies in 43 patients with severe pulmonary hypertension was not associated with a survival benefit, although improvement in functional class and/or fall in pulmonary vascular resistance >20% following treatment identified patients with improved survival. Standard prognostic markers in COPD have limited value in patients with pulmonary hypertension. This study identifies variables that predict outcome in this phenotype. Despite poor prognosis, our data suggest that further evaluation of targeted therapies is warranted.

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).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.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.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 (R(2) = 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; p0.0001). CMR-estimated PVR reliably identified invasive PVR ≥3 Wood units (WU) with a high degree of accuracy, the area under the ROC curve was 0.94 (0.88 to 0.99; p0.0001).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.

Background Collateral ventilation has been proposed as a mechanism of compensation of respiratory function in obstructive lung diseases but observations of it in vivo are limited. The assessment of collateral ventilation with an imaging technique might help to gain insight into lung physiology and assist the planning of new bronchoscopic techniques for treating emphysema. Objective To obtain images of delayed ventilation that might be related to collateral ventilation over the period of a single breath-hold in patients with chronic obstructive pulmonary disease (COPD). Methods Time-resolved breath-hold hyperpolarised 3 He MRI was used to obtain images of the progressive influx of polarised gas into initially non-ventilated defects. Results A time-series of images showed that 3 He moves into lung regions which were initially non-ventilated. Ventilation defects with delayed filling were observed in 8 of the 10 patients scanned. Conclusions A method for direct imaging of delayed ventilation within a single breath-hold has been demonstrated in patients with COPD. Images of what is believed to be collateral ventilation and slow filling of peripheral airspaces due to increased flow resistance are presented. The technique provides 3D whole-lung coverage with sensitivity to regional information, and is non-invasive and non-ionising.

Echocardiography is widely used in the investigation of patients with suspected SSc-associated pulmonary arterial hypertension (SSc-PAH). We investigated whether CT pulmonary angiography (CTPA) provides additive diagnostic value.Data for 89 consecutive patients with suspected SSc-PAH undergoing echocardiography, CTPA and right heart catheterization were reviewed. Pulmonary artery diameter (dPA) and ascending aorta diameter (dAA), right and left ventricular diameter (dRV and dLV) and grade of tricuspid regurgitation (TR(CT)) measured at CTPA and tricuspid gradient (TG(ECHO)) at echocardiography were retrieved. A predictive equation for mean pulmonary arterial pressure (mPAP) was derived using multivariate linear regression. Multivariate Cox regression analysis was then used to assess the prognostic strength of CTPA parameters and TG(ECHO).Absolute measures of dPA and dRV correlated weakly with mPAP. However, dPA : dAA and dRV : dLV showed stronger correlations with mPAP (dPA : dAA r = 0.42, P 0.001; dRV : dLV r = 0.51, P 0.001). dRV : dLV correlated more strongly with pulmonary vascular resistance than did dPA : dAA (r = 0.63 vs 0.39, P both0.001). dPA : dAA and TG(ECHO) were independent predictors of mPAP. A derived CT/echo composite index had a higher predictive accuracy (area under the curve = 0.95) than dPA : dAA or TG(ECHO) although negative predictive value (NPV) was only 77%. Combining the CT/echo composite index with presence or absence of TR(CT) increased NPV to 100% although this observation requires further validation. dRV : dLV was the strongest prognostic factor.In suspected SSc-PAH, cardiac chamber and great vessel measurements at CTPA correlate with pulmonary haemodynamics and predict survival. In combination with echocardiography CTPA increases diagnostic accuracy and may identify other potential causes of breathlessness.

Introduction Recent studies have suggested that the coexistence of emphysema and fibrosis alters clinical outcome. The aim of this study was to investigate the comparative clinical characteristics, pulmonary function, haemodynamics and right ventricular (RV) function and outcome in patients with pulmonary hypertension associated with combined pulmonary fibrosis and emphysema (PH-CPFE), chronic obstructive pulmonary disease (PH-COPD) and interstitial lung disease (PH-ILD). Methods In 79, incident patients with pulmonary hypertension associated with respiratory disease, cardiovascular magnetic resonance imaging was performed at 1.5T. Emphysema and fibrosis were scored on high resolution computed tomography scans. Demographic data, lung function tests and right heart catheterisation were also performed. Results Patients with pulmonary hypertension associated with combined pulmonary fibrosis and emphysema syndrome had lower right ventricular ejection fraction when compared to both patients with PH-COPD and PH –ILD (p < 0.05). At Kaplan-Meier analysis, patients with PH-CPFE patients had significantly worse outcome than those with PH-COPD (p = 0.015), and borderline worse outcome than patients with PH-ILD (p = 0.050), [Figure][1] . 48 of 94 patients were diagnosed with severe PH-RESP, defined at mPAP≥40 mmHg. WHO functional class (p = 0.036), TLCO (p = 0.019), RVEF (p = 0.033) were significant independent predictors of outcome in patients with severe PH-RESP. Conclusion Patients with severe PH-RESP have a dire clinical outcome. RVEF is an independent predictor of adverse outcome in these patients and may be a powerful biomarker for use in clinical trials of targeted therapy in patients with pulmonary hypertension associated with lung disease, particularly given the unreliable performance of echocardiography in patients with advanced lung disease. ![Abstract S120 Figure 1][2] Abstract S120 Figure 1 Kaplan Meier plot showing survival of patients with pulmonary hypertension associated with combined fibrosis and emphysema (PH-CPFE) in comparison to pulmonary hypertension interstitial lung disease (PH-ILD) and pulmonary hypertension associated with COPD (PH-COPD) [1]: #F1 [2]: pending:yes