Search

Aims Pulmonary arterial hypertension (PAH) is a rare but serious disease associated with high mortality if left untreated. This study aims to assess the prognostic cardiac magnetic resonance (CMR) features in PAH using machine learning. Methods and results Seven hundred and twenty-three consecutive treatment-naive PAH patients were identified from the ASPIRE registry; 516 were included in the training, and 207 in the validation cohort. A multilinear principal component analysis (MPCA)-based machine learning approach was used to extract mortality and survival features throughout the cardiac cycle. The features were overlaid on the original imaging using thresholding and clustering of high- and low-risk of mortality prediction values. The 1-year mortality rate in the validation cohort was 10%. Univariable Cox regression analysis of the combined short-axis and four-chamber MPCA-based predictions was statistically significant (hazard ratios: 2.1, 95% CI: 1.3, 3.4, c-index = 0.70, P = 0.002). The MPCA features improved the 1-year mortality prediction of REVEAL from c-index = 0.71 to 0.76 (P ≤ 0.001). Abnormalities in the end-systolic interventricular septum and end-diastolic left ventricle indicated the highest risk of mortality. Conclusion The MPCA-based machine learning is an explainable time-resolved approach that allows visualization of prognostic cardiac features throughout the cardiac cycle at the population level, making this approach transparent and clinically interpretable. In addition, the added prognostic value over the REVEAL risk score and CMR volumetric measurements allows for a more accurate prediction of 1-year mortality risk in PAH.

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.

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

Introduction: For clinical trials it is important to know the repeatability and sensitivity to change of study end-points. The aim of this study was to compare non-invasive candidate end-points in patients with pulmonary arterial hypertension (PAH). Methods: We examined 2 field walking tests: the six minute walk test (6MWT) and the incremental shuttle walking test (ISWT) and 2 tests of RV function: NT-proBNP and cardiac magnetic resonance imaging (cMRI). Patients with PAH underwent 6MWT, ISWT, NT-proBNP and cMRI (visit 1). At follow-up at around 6 months the investigations were repeated x2 within 24 hours (visits 2 and 3). Test-retest repeatability (visits 2 vs 3) and change with therapy (visit 2 minus visit 1) were assessed by the intraclass correlation coefficient (ICC) and a paired t-test respectively. Results: Of 44 patients, 40 completed the study; 27 patients underwent initiation or escalation of PAH therapy and 13 were stable on therapy. For all patients the ICC for the ISWT was 0.99, 6MWT 0.99, NT-proBNP 0.72, right ventricular end-systolic volume (RVESV) 0.98 and right ventricular ejection fraction (RVEF) 0.83. Following initiation or escalation of therapy there was an increase in ISWT, mean difference +40m (standard deviation (SD) 79), p=0.02 and 6MWT distance, +35m (SD 79) p=0.04, a reduction in RVESV -20ml (SD 30) p=0.002, and an increase in RVEF, +4% (SD 9), p=0.04 respectively. There was no significant change in NT-proBNP, -206 pg/m (SD 684), p=0.15. Conclusion: ISWT and 6MWT had excellent repeatability and are sensitive to change in PAH. CMRI but not NT-proBNP has excellent repeatability and is sensitive to change.

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

Pulmonary hypertension is a condition of varied etiology, commonly associated with poor clinical outcome. Patients are categorized on the basis of pathophysiological, clinical, radiologic, and therapeutic similarities. Pulmonary arterial hypertension (PAH) is often diagnosed late in its disease course, with outcome dependent on etiology, disease severity, and response to treatment. Recent advances in quantitative magnetic resonance imaging (MRI) allow for better initial characterization and measurement of the morphologic and flow-related changes that accompany the response of the heart-lung axis to prolonged elevation of pulmonary arterial pressure and resistance and provide a reproducible, comprehensive, and noninvasive means of assessing the course of the disease and response to treatment. Typical features of PAH occur primarily as a result of increased pulmonary vascular resistance and the resultant increased right ventricular (RV) afterload. Several MRI-derived diagnostic markers have emerged, such as ventricular mass index, interventricular septal configuration, and average pulmonary artery velocity, with diagnostic accuracy similar to that of Doppler echocardiography. Furthermore, prognostic markers have been identified with independent predictive value for identification of treatment failure. Such markers include large RV end-diastolic volume index, low left ventricular end-diastolic volume index, low RV ejection fraction, and relative area change of the pulmonary trunk. MRI is ideally suited for longitudinal follow-up of patients with PAH because of its noninvasive nature and high reproducibility and is advantageous over other biomarkers in the study of PAH because of its sensitivity to change in morphologic, functional, and flow-related parameters. Further study on the role of MRI image based biomarkers in the clinical environment is warranted.

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.

Pulmonary arterial hypertension (PAH) is a severe, low survival and rapidly progressive disease, characterised by an increase in the distal pulmonary vascular resistance and decrease in pulmonary compliance. The current standard procedure for PAH diagnosis and therapy response assessment is right heart catheterisation (RHC). Although if performed in a specialist centre, the severe complications associated with RHC are reduced, non-invasive alternatives are desirable. Windkessel models have been previously proposed[1], [2] to estimate the overall pulmonary system resistance and compliance.

Introduction: In contrast to the systemic arterial system, the association between age and compliance in the pulmonary circulation has to date not been investigated in vivo. The aim of this study was to evaluate the impact of age on pulmonary arterial compliance in health and in patients with pulmonary arterial hypertension (PAH). Methods: Consecutive patients with No PH (mPAP Results: 151 patients with PAH (57 underwent follow up RHC), 83 patients with No PH were identified and 34 healthy volunteers were included. Main pulmonary artery compliance correlated with age in patients with No PH (r=0.491, p Discussion: Advancing age is independently associated with pulmonary arterial compliance in health and disease. In contrast to younger patients, pulmonary arterial compliance does not increase in response to PAH therapy in older patients.

Background In contrast to the considerable literature on the prognostic value of right ventricular metrics at baseline and follow-up in PAH, the prognostic value of right atrial size and function has been less well studied. The aim of this study was to compare the prognostic value of right atrial length, area and volume measurements in treatment naive patients with PAH and the impact of treatment. Methods Patients with PAH who underwent MRI at baseline and follow up on a 1.5 T MRI scanner were identified. Maximum and minimum right atrial length, area and volume were measured on two and four chamber images. Survival analysis, using univariate and multivariate Cox proportional hazards regression analysis was performed. Results 154 patients were identified, of whom 18 died. Change in minimal right atrial volume predicted mortality (p=0.028). Change in maximal right atrial volume, stroke volume and ejection fraction did not predict mortality, p=0.228, p=0.229 and p=0.915 respectively. Other than change in minimum two chamber right atrial area predicting mortality (p=0.049), individual changes in length and area measurements in the 4 chamber images were not prognostic. Right atrial length and area measures were highly reproducible intraclass correlation coefficient 0.910 to 0.984. Conclusion Change in minimal right atrial volume predicts mortality and maybe of value in the serial evaluation of patients on PAH therapy.

Introduction: Pulmonary arterial hypertension is defined at cardiac catheterization as a mPAP≥ 25 mmHg and a pulmonary arterial wedge pressure (PAWP) ≤15mmHg. The presence of cardiac comorbidities is associated with a poorer response to therapy in patients with PAH and left ventricular diastolic dysfunction may exist even in the presence of a normal resting PAWP. The aim of this study was to use left atrial volume as a surrogate of left ventricular diastolic dysfunction in patients with normal PAWP and assess its impact on treatment response in PAH. Methods: We studied 85 treatment naive patients with PAH with an MRI at baseline and follow up at 1 year (median 1year IQR 0.8). Patients were grouped by LA volume threshold of 34ml/m2 based on established literature. Changes in biventricular volume, mass and function were compared. Results: Compared to patients with elevated LA volume (n=31), those with normal LA volume (n=54) had greater treatment response with increase in change in RV ejection fraction, LV stroke volume, LV end diastolic volume and diastolic interventricular septal angle (p=0.032, p=0.001, p=0.001 and p=0.025 respectively). Patients with normal LA volume had a significant improvement in RV ejection fraction between baseline and follow up (mean increase 9%, p Conclusion: This study shows that in patients meeting the haemodynamic criteria for PAH, patients with an elevated LA volume had poor response to PAH therapy. Further work to better characterize this PAH phenotype and recognize the importance of comorbidities in predicting response to therapy is required.

Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (mPAP) ≥ 25mmHg at right heart catheterization. An mPAP of 21-24mmHg is termed borderline PH. This study investigates cardiac magnetic resonance (CMR) imaging characteristics of patients with borderline PH. Consecutive patients who underwent CMR at 1.5T at a PH centre between April 2012 and January 2016 were identified. Exclusion criteria were non-diagnostic imaging or RHC >48 hours from CMR. All variables were compared between patients with normal mPAP (≤ 20mmHg) and a borderline group (21-24 mmHg) using an independent samples t-test and bilogistic regression. Of 1800 consecutive patients with suspected PH, 128 patients met the inclusion criteria. In the full cohort, large RVEDVI (p Subgroup analysis of patients with connective tissue disease (N=49) revealed raised systolic IVS angle (p=0.048) in borderline patients (N=22). In patients with lung disease (N=60), borderline patients (N=32) had raised RVEDVI (p=0.001), RV mass index (p=0.028) and IVS angle (p=0.05). LHD patients (N=16) with borderline pressures (N=9) had raised RVEDVI (p=0.022) and RV mass index (p=0.041). Patients with thromboembolic disease (N=36) with borderline pressures (N=18) had raised RV mass index (p=0.026). Patients with borderline PH have evidence of RV remodelling but preserved RV functional metrics when compared to patients with normal PA pressure.

Pulmonary hypertension (PH) is important in COPD as it is a predictor of hospitalization and death. The gold standard for diagnosis is right heart catheterisation (RHC), an invasive test. Patients are screened using echo, but this is less successful in COPD due to hyperinflation. The aim of this study was to assess a noninvasive model of mPAP estimation using cardiopulmonary MRI. Consecutive patients with COPD referred to a PH centre from 2012 to 2016 were reviewed. Biventricular volumes, mass and function, PA flow measurements and black blood pulmonary flow phenomenon were recorded as previously described [1, 2]. 145 of the 1864 patients in the period analysed had COPD. 80 had MRI and RHC data available. The first 40 were used as a training cohort to derive the regression equation: MRImPAP = -15.6 + (0.25xinterventricular septal angle) + (4.4xblack blood score). This equation was validated in the subsequent 40 patients. The correlation between MRI-mPAP and RHC-mPAP was 0.78 (p = 0.00). ROC in the validation cohort gave area under the curve 0.975. Using a cut-off of MR predicted mPAP of ≥25mm in the validation cohort gave 97% sensitivity and 83% specificity for the diagnosis of pulmonary hypertension in COPD. In COPD patients referred for assessment of PH a composite MRI model of black blood pulmonary flow phenomenon score and interventricular septal angle can be used as a surrogate for mPAP to diagnose PH.

Pulmonary hypertension (PH) is a heterogeneous condition. To date, no registry data exists reflecting the spectrum of disease across the five diagnostic groups encountered in a specialist referral centre. Data was retrieved for consecutive, treatment-naive cases diagnosed between 2001 and 2010 using a catheter-based approach. 1,344 patients were enrolled, with a mean follow-up of 2.9 yrs. The 3-yr survival was 68% for pulmonary arterial hypertension (PAH), 73% for PH associated with left heart disease, 44% for PH associated with lung disease (PH-lung), 71% for chronic thromboembolic PH (CTEPH) and 59% for miscellaneous PH. Compared with PAH, survival was inferior in PH-lung and superior in CTEPH (p

Introduction: Mean right atrial pressure (mRAP) is a strong haemodynamic prognostic marker in patients with pulmonary arterial hypertension. Non-invasive alternatives are desirable. The aim of this study was to evaluate trans-tricuspid flow indices as candidate cardiac magnetic resonance (CMR) imaging predictors of mRAP. Methods: 19 patients with suspected pulmonary hypertension underwent MRI and right heart catheterisation (RHC) within 24 hours. Trans-tricuspid phase contrast was performed with flow quantification. Early diastolic (E) and atrial (A) filling velocities and E wave deceleration time (DT) were measured. Results: The strongest association was between DT and mRAP (r=0.729, p=0.001), this association was independent of covariates at multivariate analysis (standardized coefficient=0.494, p=0.028). DT correlated with right ventricle (RV) volume measurements, RV end diastolic volume (r=0.603, p=0.013) and end systolic volume (r=0.513, p=0.042). E/A ratio was not significantly associated with mRAP (r=0.156, p=0.579). DT had excellent diagnostic accuracy for detection of elevated mRAP greater than or equal to 12mmHg, area under the receiver operating curve 0.98 (0.913 to 1.000). Good interobserver reproducibility was demonstrated for MR derived DT and E/A, intraclass correlation coefficients, 0.946 (0.869 to0.977) and 0.939 (0.856 to 0.976), respectively. Discussion This preliminary experience suggests that deceleration time of the E wave using trans-tricuspid phase contrast is a promising, reproducible tool in the non-invasive haemodynamic evaluation of patients with pulmonary hypertension.

Introduction: MRI is a promising tool for the prognostication of patients with pulmonary arterial hypertension (PAH). The aim of this study was to investigate the prognostic value of measurements made in the right ventricle (RV) and the pulmonary vasculature in comparison to invasive haemodynamics. Methods: Kaplan-Meier and multivariate Cox proportional hazards regression analysis evaluation of demographic data, MRI measurements of RV and pulmonary artery (PA) size and PA relative area change (RAC), and right heart catheterisation (RHC) data, before and after 2 years follow-up. Results: 482 patients were identified, 122 (25%) patients died during the follow up period of 2 ± 1.2 years. At Kaplan-Meier analysis, RV ejection fraction (RVEF) and RV end systolic volume index (RVESVI) were predictors of mortality within 2 years (log rank 14.6, p Conclusions: MRI right ventricular and pulmonary arterial metrics predict mortality independent of RHC. Loss of right ventricular function indicates high risk of mortality within 2 years, whereas loss of PA relative area change is a marker of longer term outcome.

Introduction: An MRI model derived from right ventricular (RV) measurements has been proposed for the evaluation of mean pulmonary arterial pressure (mPAP) with MRI has been proposed in the evaluation of patients with pulmonary hypertension (PH). The aim of this study was to estimate mPAP using MRI using metrics from both the RV and pulmonary artery (PA). Methods: A derivation cohort of 300 consecutive patients with suspected PH underwent RHC and MRI within 48 hours. An estimate of mPAP was derived using multivariate regression analysis of MRI measurements. The model was tested in an independent validation cohort of 140 patients with suspected PH. Comparative diagnostic accuracy of estimated mPAP derived from RV and PA indices, versus estimated mPAP derived from RV metrics alone was assessed. Results: The derivation cohort included 247 patients with PH and 53 patients with mPAP Conclusion: In addition to RV indices, PA diastolic area and relative area change measured by MRI, have incremental value for estimation of mPAP. A model using RV and PA metrics improves diagnostic accuracy over RV measurements alone.

Introduction: A cardiac MRI model has been proposed for estimation of mPAP in patients with suspected pulmonary hypertension (PH). The aim of this study was to evaluate the accuracy of MRI in PH subgroups compared to echocardiography. Methods: Patients with suspected PH between 2012 and 2014 who underwent MRI and right heart catheterisation (RHC) within 48hrs. MRI estimated mPAP (A) was defined as: -4.6 + (inter-ventricular septal angle x 0.23) + (ventricular mass index (diastolic right ventricular mass/left ventricular mass) x 16.3). Estimated mPAP was also derived using VMI measured in systole (B). Results: 440 patients with suspected PH were identified. RHC-mPAP correlated well with MRI estimated mPAP in pulmonary arterial hypertension (PAH) [r=0.70 (A) and r=0.78 (B)], patients with PH associated with respiratory disease (PH-RESP) [r=0.70 (A) and r=0.84 (B)] and patients with chronic thromboembolic PH (CTEPH) [r=0.63 (A) and r=0.74 (B)]. RHC-mPAP correlated weakly with MRI estimated mPAP (A and B) in patients with PH-left heart disease (LHD) [r=0.35 (A) and r=0.43 (B)]. MRI estimated mPAP was accurate for detecting PH in patients with PAH, PH-RESP and CTEPH (AUC 0.86-0.92), though inaccurate in patients with PH-LHD (AUC 0.68-0.73). Echocardiography had the strongest diagnostic accuracy in all subgroups (AUC 0.912-0.945). Conclusion: Echocardiography is more diagnostic than MRI in all patient subgroups. Except in patients with PH-LHD MRI derived mPAP tended to correlate more strongly with RHC-mPAP than echocardiography. This MRI model is not recommended for estimating mPAP in patients with PH-LHD, however may be a useful alternative to echocardiography in PAH, PH-RESP and CTEPH.

Introduction: Non-invasive diagnosis of pulmonary hypertension(PH) is highly desirable to eliminate right heart catheterisation(RHC) complications. Cardiopulmonary measurements of morphology and functions of the heart using MRI have shown promising results. Additional information is incorporated with MRI based mathematical models of pulse wave transmission and impedance of the pulmonary circulation. The aim of this study is to evaluate the added diagnostic value obtained by combining mathematical and cardiopulmonary metrics together with artificial intelligence(AI) classifiers. Methods: 72 patients suspected of PH, underwent RHC and MRI within 48hrs. 57 patients(mPAP≥25mmHg) were included in the PH group (44±14 mmHg) while 17 formed the control group (21±3 mmHg). A 0D and a 1D model(Lungu et.al,2014 Biomech 47:2941-2947) were applied to estimate: reflected (wasted) energy in the pulmonary circuit(W pb /W ptotal ), distal pulmonary resistance(R d ) and total pulmonary compliance(C). Cardiopulmonary MRI markers were also derived: MPA relative area change(RAC), right ventricular mass index(RVMI) and systolic septal angle. All metrics were passed to a random forest classifier and trained to decide between PH and NoPH individuals. Results: The classifier results, validated with leave-one-out-cross-validation, showed that 92% of patients were correctly classified, whereas the performance of the individual markers was∼75%, tested by maximisation of the Youden index. Conclusions: The findings support the hypothesis that combining PH biomarkers with AI classification algorithms increases the diagnostic power of these non-invasive measurements and models in PH.

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 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.

The aim of this study was to evaluate the clinical use of magnetic resonance imaging measurements related to pulmonary artery stiffness in the evaluation of pulmonary hypertension (PH).A total of 134 patients with suspected PH underwent right heart catheterization (RHC) and magnetic resonance imaging on a 1.5-T scanner within 2 days. Phase contrast imaging at the pulmonary artery trunk and cine cardiac views were acquired. Pulmonary artery area change (AC), relative AC (RAC), compliance (AC/pulse pressure from RHC), distensibility (RAC/pulse pressure from RHC), right ventricular functional indices, and right ventricular mass were all derived. Regression curve fitting identified the statistical model of best fit between RHC measurements and pulmonary artery stiffness indices. The diagnostic accuracy and prognostic value of noninvasive AC and RAC were also assessed.The relationship between pulmonary vascular resistance and pulmonary artery RAC was best reflected by an inverse linear model. Patients with mild elevation in pulmonary vascular resistance (4 Woods units) demonstrated reduced RAC (P = 0.02) and increased right ventricular mass index (P0.0001) without significant loss of right ventricular function (P = 0.17). At follow-up of 0 to 40 months, 18 patients with PH had died (16%). Analysis of Kaplan-Meier plots showed that both AC and RAC predicted mortality (log-rank test, P = 0.046 and P = 0.012, respectively). Area change and RAC were also predictors of mortality using univariate Cox proportional hazards regression analysis (P = 0.046 and P = 0.03, respectively).Noninvasive assessment of pulmonary artery RAC is a marker sensitive to early increased vascular resistance in PH and is a predictor of adverse outcome.

Double inversion recovery (DIR) "black blood" MRI suppresses the signal from flowing blood, slow flowing blood causes incomplete suppression resulting in pulmonary blood flow artefact (PFA). This study examines the diagnostic utility and prognostic value of a PFA scoring system in a mixed cohort of patients with pulmonary hypertension (PH).DIR-MRI images were reviewed for 233 patients referred with suspected PH who underwent right heart catheterisation (RHC) within 48 h of MR. The degree of PFA was visually scored in all patients from 0 to 5 (0 = absent, 1 = segmental, 2 = lobar, 3 = distal main, 4 = proximal main and 5 = trunk). Pulmonary artery (PA), aorta (Ao), and PA main branch diameters were measured from which PA/Ao ratios and mean PA branch diameters (MPAB) were calculated.PFA1 demonstrated high sensitivity (86%) and specificity (85%) for the diagnosis PH in our mixed patient cohort. A good correlation was found with PFA and haemodynamic parameters, PVR (r = 0.70), mPAP (r = 0.65) and CI (r = -0.53). PFA predicted mortality (P = 0.005) during the mean follow-up for 19 months. PFA scoring demonstrated good inter-observer agreement (k = 0.83).PFA scoring is of diagnostic and prognostic value in the assessment of patients with suspected PH. and is a predictor of mortality.• A simple magnetic resonance method of assessing pulmonary blood flow is presented • This involves a qualitative scoring system of black blood pulmonary flow artefacts • This is simple to perform and seems reproducible in pulmonary hypertension patients • The degree of artefact correlates well with right heart catheter measurements • Prominent pulmonary flow artefact predicts mortality in patients with pulmonary hypertension.

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

Background: We were finding volunteers for functional magnetic resonance imaging studies with abnormalities requiring referral surprisingly frequently. The bioethics surrounding the incidental findings are not straightforward and every imaging institution will encounter this situation in their normal volunteers. Yet the implications for the individuals involved may be profound. Should all participants have review of their imaging by an expert and who should be informed? Methods: The normal volunteers that were imaged with magnetic resonance (MR) which were reviewed by a consultant neuroradiologist. All participants completed a volunteer consent form in addition to a standard departmental MR safety screening form. The volunteer screening form requires the general practitioner details to be completed and asks the participant to consider closely the possibility and implications of finding an unexpected but potentially serious abnormality before signing. Results: 525 different individuals were scanned as normal volunteers, the mean age was 35-years and 330 were males. Of these 525, 46 had definite significant abnormalities (8.8%), mean age 50-years. Conclusion: We have found a high rate of incidental abnormalities amongst individuals participating in imaging studies at our institution. It is our current practice to inform the research study participant of the findings, counsel them and inform their primary care physician. We think that it is advisable for researchers utilising MR imaging of the brain to have access to trained neuroradiologists, a protocol in place to deal with this problem and take consent in a way that allows the participant to realise the possibility of an abnormal finding.

Purpose Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently affected by the condition but have worse outcome as compared to females. We sought to characterise the sex related differences in right ventricular remodelling in age matched male and female patients with IPAH using cardiac magnetic resonance imaging (MRI). Methods A case controlled pair-matched study was conducted with patients matched by age and sex. Steady state free precession (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass measurements were corrected for age, sex and BSA according to reference data. Results 40 age and sex matched patients with IPAH were identified. The mean age was 57 (SD 17) in both male and female cohorts. Men had proportionally lower right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no significant difference in RV mass or haemodynamic indices of mPAP and PVR between males and females. Conclusion Male patients with IPAH have proportionally worse RV function despite similar afterload. We hypothesise that adaptive remodelling of the RV in response to increased afterload in IPAH is more effective in females.

We investigated the role of magnetic resonance angiography (MRA) in the early follow-up of patients after stereotactic radiosurgery (STRS) for cerebral arteriovenous malformations (AVMs) and determined the influence of individual morphological factors of AVMs in early response to treatment. A group of 40 patients (41 AVMs) consented to a dedicated 1.5-T MR protocol 12 months after receiving STRS for a brain AVM. In addition to standard spin echo sequences, 3-D contrast-enhanced sliding interleaved Ky MRA (CE-SLINKY) and dynamic time-resolved subtraction angiography (MR-DSA) were performed. Nidal volumes were calculated using CE-SLINKY data in patients with a persisting arteriovenous shunt. Planning angiographic data was investigated in all 40 patients. The following AVM factors were used in the statistical analysis to determine their role in nidus obliteration: (1) maximum linear dimension, (2) nidal volume, (3) AVM location (4) nidal morphology, (5) venous drainage, (6) “high-flow angiographic change”, (7) prior embolization, and (8) dose reduction. Complete nidal obliteration was found in 9 patients, 26 showed greater than 50% nidal reduction and 6 had less than 50%. Two AVM factors, venous drainage and AVM location, were found to significantly correlate with rate of obliteration. We successfully demonstrated the use of MRA to quantitatively assess the response of AVMs to STRS. Two AVM factors, venous drainage and AVM location were found to correlate with rate of obliteration prior to the application of the Bonferroni correction, but if this more rigorous statistical test was applied then none of the factors was found to be significant.

Arteriovenous malformations of the brain are complex vascular lesions that are an important cause of death and long-term disability. Currently, catheter angiography (CA) is the reference standard procedure for the diagnosis and follow-up of treated arteriovenous malformations (AVMs). This is an invasive procedure with potential risks. Magnetic resonance angiography (MRA) is commonly used in neurovascular imaging as a non-invasive alternative. Various MRA techniques have been used in the diagnosis and follow-up of AVMs but these have suffered from lack of temporal or spatial resolution. In this 60-patient study we describe the combination of two techniques: dynamic magnetic resonance digital subtraction angiography with a high temporal resolution, and a non-dynamic contrast-enhanced time-of-flight sequence with a high spatial resolution technique, in the assessment of AVM. The results showed an excellent correlation between MRA and CA measurement of both maximum linear dimension and AVM nidus volume.

Purpose The purpose of our study was to assess the diagnostic accuracy and reliability of contrast enhanced MR lung perfusion compared to perfusion scintigraphy in patients with CTEPH. Methods and Materials Retrospective analysis of patients investigated for CTEPH who had MR lung perfusion, perfusion scintigraphy and CTPA performed within a time interval of 5 days. The MR images were acquired using a time resolved 3D spoiled gradient echo sequence. The sequence parameters: TE 1.1 ms, TR 2.5 ms, flip angle of 30°, FOV=48 cm 2 , slice thickness of 5 mm, average of 32 slices and frame rate was 2 acquisitions per second. This was a breathhold sequence obtained after 0.05 ml/kg of Gadovist injection at 5 ml/s followed by a 20 ml saline flush. The subtraction images and positive enhancement dataset were analysed in the coronal plane. Four static views perfusion scintigraphy views were obtained. Final diagnosis of CTEPH or non-CTEPH was made at a multidisciplinary meeting following detailed multi-modality assessment. Results 27 patients had a diagnosis of CTEPH and 55 patients were diagnosed as non-CTEPH. In the CTEPH group, MRI lung perfusion diagnosed 26 patients as CTEPH and 1 patient with distal surgically inaccessible disease as non-CTEPH. In the non-CTEPH group, four patients were diagnosed as CTEPH and 48 patients were identified as non-CTEPH and three MRI were considered non-diagnostic. MR lung perfusion was not performed in 11 patients due to impaired renal function or patient unable to tolerate breathhold. None of the surgically accessible disease was missed with either modality. The MR lung perfusion had a sensitivity of 96%, specificity of 92%, PPV of 87%, NPV of 98% and accuracy of 94% for diagnosing CTEPH. Perfusion scintigraphy had a sensitivity of 93%, specificity of 90%, PPV of 83%, NPV of 96% and accuracy of 91%. Conclusion Our results show that MR lung perfusion compared to 4-view static perfusion scintigraphy has an overall higher accuracy compared to perfusion scintigraphy and has a role in assessment of patients with suspected CTEPH.

Background The incremental prognostic significance of late gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) imaging in the clinical assessment of patients with pulmonary hypertension remains uncertain. We aimed to determine the prognostic value of LGE-CMR imaging in patients with pulmonary hypertension at 1-year follow-up. Methods We studied consecutive patients with suspected pulmonary hypertension at a specialist referral centre who underwent right heart catheterisation and CMR with LGE imaging within 48 h. Short axis late-enhancement imaging was done with a three-dimensional-gradient spoiled echo sequence on a 1.5T scanner. Three groups were identified: no late enhancement of the myocardium, late enhancement at the hinge insertion points (LGE-IP), and late enhancement involving the hinge insertion points and the interventriclar septum (LGE-S). Prognostic significance was assessed with univariate and multivariate Cox proportional hazards regression analysis. Findings Of 194 patients, 162 had pulmonary hypertension. Late gadolinium enhancement was identified in 135 (83%) of 162 patients with pulmonary hypertension; 29% (47/162) demonstrated LGE-S. The presence of LGE-S (hazard ratio 3·66, 95%CI 1·68–7·98; p=0·001), right ventricle ejection fraction (0·97, 0·94–1·00; p=0·042), mixed venous oxygen saturations (0·955, 0·91–1·00; p=0·044), female sex (0·40, 0·18–0·90; p=0·026), and WHO functional class (2·35, 1·14–4·86; p=0·021) predicted mortality at 1 year. In multivariate analysis, LGE-S remained a significant predictor of mortality independent of significant covariate predictors of mortality (p=0·018). Interpretation Late gadolinium enhancement of the interventricular septum in addition to the insertion points is an independent marker of adverse outcome, resulting in a roughly four-fold increase in mortality at 1 year. This CMR technique might prove to be the new gold standard for assessment of disease severity in pulmonary hypertension, with incremental value for the identification of treatment failure. Funding National Institute for Health Research.

Introduction and Objectives The aim of this study was to assess the clinical utility of quantitative MR indices of cardiac morphology and function in a large cohort of patients with pulmonary hypertension (PH). Methods We retrospectively studied 233 consecutive patients with suspected PH who underwent cardiac MRI and right heart catheterisation (RHC) within 48 h. Four chamber and short axis (SA) CINE images were acquired using cardiac gated multi-slice imaging with a steady state free precession sequence at 1.5T. The diagnostic and prognostic significance of quantitative measurements of right ventricular morphology and function were assessed. Results Right ventricular end-diastolic mass index was the measurement with the strongest correlation with mPAP (r=0.74) and the highest diagnostic accuracy for the detection of PH (area under the receiver operator curve of 0.91). During the mean follow-up of 18 months (0–36 months), 36 patients with PH died. Right ventricular ejection fraction (p=0.003), right ventricular stroke volume index (p=0.03) and IVC size (p=0.01) were the MR predictors of mortality across the subgroups of PH. MR measurements of right ventricular ejection fraction (p=0.004), right ventricular stroke volume index (p=0.02), and left ventricular diastolic eccentricity index (p=0.005), all predicted mortality in patients with pulmonary arterial hypertension, Abstract S70 figure 1 below shows the Kaplan–Meier plots the MR predictors of mortality in PAH. IVC size (p=0.018) was an independent predictor of mortality in the full cohort of patients with PH, and diastolic eccentricity index (p=0.037) was an independent predictor of adverse outcome in patients with PAH. Conclusion Cardiac MRI provides a comprehensive assessment of right ventricular morphology and function in patients with PH. This study confirms the diagnostic and prognostic applicability of MRI in unselected patients with PH of varied aetiologies in a practical clinical setting.

Objectives The goal of this study was to determine the prognostic value of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) features in patients with pulmonary hypertension. Background The prognostic significance of LGE in the clinical assessment of patients with pulmonary hypertension remains uncertain. Methods Consecutive patients with suspected pulmonary hypertension seen at a specialist pulmonary hypertension referral center who underwent right heart catheterization and CMR with LGE imaging within 48 h were identified. Short-axis late-enhancement imaging was performed using a 3-dimensional gradient spoiled echocardiography sequence on a 1.5-T scanner. Three groups were identified: 1) no late enhancement of the myocardium; 2) late enhancement at the right ventricular insertion points (LGE-IP); and 3) late enhancement involving the right ventricular insertion points and the interventricular septum (LGE-S). Results Of 194 patients, 162 had pulmonary hypertension. LGE was identified in 135 of 162 (83%) patients with pulmonary hypertension, and 47 (29%) of patients demonstrated LGE-S. Patients with LGE-S had significantly higher right ventricular end-diastolic volume index (p = 0.013) and lower mixed venous oxygen saturation (p = 0.045) than patients with LGE-IP alone. The presence of LGE-S (p = 0.022), but not LGE-IP alone, right ventricular end-systolic volume (p = 0.045), right ventricular ejection fraction (p = 0.034), mixed venous oxygen saturation (p = 0.021), mean right atrial pressure (0.027), and male sex (p = 0.002) predicted mortality. At multivariate analysis, male sex was the only significant predictor of mortality independent of covariate predictors (p = 0.027). Conclusions The presence of LGE at the right ventricular insertion points is suggestive of the presence of pulmonary hypertension. LGE may also be more extensive, involving the septum; however, after multivariable analysis including other factors associated with pulmonary hypertension, septal LGE was not associated with an increase in overall mortality.

Results 30 consecutive patients with suspected pulmonary hypertension were studied by both independent observers. RV mass measured in systole had higher ICC agreement than diastole (0.983 verses 0.947) and showed less bias at Bland-Altman analysis, 1.9g compared to 8.7g, Figure 1. Of note, RV mass measurements were significantly higher when measured in systole than diastole, with a mean difference of 10g (95% confidence interval of 6.6 to 13.2, p

Background Cardiovascular Magnetic Resonance (CMR) imaging is accurate and reproducible for the assessment of right ventricular (RV) morphology and function. However, the diagnostic accuracy of CMR derived RV measurements for the detection of pulmonary hypertension (PH) in the assessment of patients with suspected PH in the clinic setting is not well described. Methods We retrospectively studied 233 consecutive treatment naïve patients with suspected PH including 39 patients with no PH who underwent CMR and right heart catheterisation (RHC) within 48hours. The diagnostic accuracy of multiple CMR measurements for the detection of mPAP ≥ 25 mmHg was assessed using Fisher’s exact test and receiver operating characteristic (ROC) analysis. Results Ventricular mass index (VMI) was the CMR measurement with the strongest correlation with mPAP (r = 0.78) and the highest diagnostic accuracy for the detection of PH (area under the ROC curve of 0.91) compared to an ROC of 0.88 for echocardiography calculated mPAP. Late gadolinium enhancement, VMI ≥ 0.4, retrograde flow ≥ 0.3 L/min/m2 and PA relative area change ≤ 15% predicted the presence of PH with a high degree of diagnostic certainty with a positive predictive value of 98%, 97%, 95% and 94% respectively. No single CMR parameter could confidently exclude the presence of PH. Conclusion CMR is a useful alternative to echocardiography in the evaluation of suspected PH. This study supports a role for the routine measurement of ventricular mass index, late gadolinium enhancement and the use of phase contrast imaging in addition to right heart functional indices in patients undergoing diagnostic CMR evaluation for suspected pulmonary hypertension.