Judith Hurdman

Pulmonary hypertension in COPD: results from the ASPIRE registry

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-naïve 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.

Noninvasive estimation of PA pressure, flow, and resistance with CMR imaging: derivation and prospective validation study from the ASPIRE registry.

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 (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; p < 0.0001). 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; p < 0.0001). 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.

Diagnostic accuracy of cardiovascular magnetic resonance imaging of right ventricular morphology and function in the assessment of suspected pulmonary hypertension results from the ASPIRE registry

BackgroundCardiovascular 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.MethodsWe 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.ResultsVentricular 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.ConclusionCMR 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.

3D contrast-enhanced lung perfusion MRI is an effective screening tool for chronic thromboembolic pulmonary hypertension: results from the ASPIRE Registry

Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism potentially curable by surgery. Perfusion scintigraphy is currently advocated as the imaging modality of choice to exclude CTEPH due to its high sensitivity. We have evaluated the diagnostic utility of lung perfusion MRI. Methods Consecutive patients attending a pulmonary hypertension referral centre undergoing lung perfusion MRI, perfusion scintigraphy, CT pulmonary angiography (CTPA) and right heart catheterisation within 14 days were identified. Results Of 132 patients, 78 were diagnosed as having CTEPH. Lung perfusion MRI correctly identified 76 patients as having CTEPH with an overall sensitivity of 97%, specificity 92%, positive predictive value 95% and negative predictive value 96% compared with perfusion scintigraphy (sensitivity 96%, specificity 90%) and CTPA (sensitivity 94%, specificity 98%). No cases of surgically accessible CTEPH were missed with either modality. Conclusions Lung perfusion MRI has high sensitivity equivalent to perfusion scintigraphy in diagnosing CTEPH but does not require ionising radiation, making it an attractive initial imaging modality to assess patients with suspected CTEPH.

Comparison of the Diagnostic Utility of Cardiac Magnetic Resonance Imaging, Computed Tomography, and Echocardiography in Assessment of Suspected Pulmonary Arterial Hypertension in Patients with Connective Tissue Disease

Objective. Pulmonary arterial hypertension (PAH) is a life-threatening complication of connective tissue diseases (CTD). Our aim was to compare the diagnostic utility of noninvasive imaging modalities, i.e., magnetic resonance imaging (MRI), computed tomography (CT), and echocardiography, in evaluation of these patients. Methods. In total, 81 consecutive patients with CTD and suspected PH underwent cardiac MRI, CT, and right heart catheterization (RHC) within 48 hours. Functional cardiac MRI variables [ventricle areas and ratios, delayed myocardial enhancement, position of the interventricular septum, right ventricular mass, ventricular mass index (VMI), and pulmonary artery distensibility] were all evaluated. The pulmonary artery size, pulmonary artery/aortic ratio (PA/Ao), left and right ventricular (RV) diameter ratio, RV wall thickness, and grade of tricuspid regurgitation were measured on CT. Tricuspid gradient (TG) and size of the RV were assessed using echocardiography. Results. In our study of 81 patients with CTD, 55 had PAH, 22 had no PH, and 4 had PH owing to left heart disease. There was good correlation between mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) measured by RHC and VMI derived from MRI (mPAP, r = 0.69, p < 0.001; PVR, r = 0.78, p < 0.001) and systolic area ratio (mPAP, r = 0.69, p < 0.001; PVR, r = 0.68, p < 0.001) and TG derived from echocardiography (mPAP, r = 0.84, p < 0.001; PVR, r = 0.76, p < 0.001). In contrast, CT measures showed only moderate correlation. MRI and echocardiography each performed better as a diagnostic test for PAH than CT-derived measures: VMI ≥ 0.45 had a sensitivity of 85% and specificity 82%; and TG ≥ 40 mm Hg had a sensitivity of 86% and specificity 82%. Univariate Cox regression analysis showed the MRI measurements were better at predicting mortality. Patients with RV end diastolic volume < 135 ml had a better prognosis than those with a value > 135 ml, with a 1-year survival of 95% versus 66%, respectively. Conclusion. In patients with CTD and suspected PAH, cardiac MRI and echocardiography have greater diagnostic utility than CT in the assessment of patients with suspected PAH, and MRI has prognostic value.

Pulmonary artery relative area change detects mild elevations in pulmonary vascular resistance and predicts adverse outcome in pulmonary hypertension.

ObjectiveThe 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). Materials and MethodsA 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. ResultsThe 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 (P < 0.0001) 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). ConclusionsNoninvasive assessment of pulmonary artery RAC is a marker sensitive to early increased vascular resistance in PH and is a predictor of adverse outcome.

Prognostic value of cardiovascular magnetic resonance imaging measurements corrected for age and sex in idiopathic pulmonary arterial hypertension.

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.

Management dilemmas in acute pulmonary embolism

Background Physicians treating acute pulmonary embolism (PE) are faced with difficult management decisions while specific guidance from recent guidelines may be absent. Methods Fourteen clinical dilemmas were identified by physicians and haematologists with specific interests in acute and chronic PE. Current evidence was reviewed and a practical approach suggested. Results Management dilemmas discussed include: sub-massive PE, PE following recent stroke or surgery, thrombolysis dosing and use in cardiac arrest, surgical or catheter-based therapy, failure to respond to initial thrombolysis, PE in pregnancy, right atrial thrombus, role of caval filter insertion, incidental and sub-segmental PE, differentiating acute from chronic PE, early discharge and novel oral anticoagulants. Conclusion The suggested approaches are based on a review of the available evidence and guidelines and on our clinical experience. Management in an individual patient requires clinical assessment of risks and benefits and also depends on local availability of therapeutic interventions.

Lung Morphology Assessment with Balanced Steady-State Free Precession MR Imaging Compared with CT

PURPOSE To evaluate the utility of 1.5-T noncontrast magnetic resonance (MR) imaging of the lung parenchyma and to compare it with computed tomography (CT) in the assessment of interstitial lung disease and other morphologic lung abnormalities. MATERIALS AND METHODS Institutional review board approval was obtained for retrospective image analysis. A total of 236 patients who underwent MR imaging and CT as part of their assessment for suspected pulmonary hypertension were included in this study. Lung MR imaging was performed with a 1.5-T system as a stack of axial two-dimensional balanced steady-state free precession (bSSFP) acquisitions. Two radiologists independently evaluated CT and MR images for various morphologic abnormalities, such as pulmonary fibrosis, pleural and mediastinal disease, solid lesions, bronchial disease, and emphysema. Κ statistics were used to measure interobserver agreement. RESULTS Sensitivity and specificity of MR imaging in the identification of pulmonary fibrosis (n = 46) were 89% (95% confidence interval: 77%, 96%) and 91% (95% confidence interval: 76%, 98%), respectively, when compared with CT. In comparison to CT, MR imaging depicted 75% of ground-glass opacities. Nine of the 12 noncalcified nodules were identified on MR images. Lung nodules (75%, κ = 0.71) and effusions (100%, κ = 0.89) were also well visualized on MR images. MR imaging was however less effective in depicting emphysema (16%, κ = 0.60) and minor fibrosis (67%, κ = 0.79). CONCLUSION This study shows bSSFP MR imaging is inferior to CT in imaging parenchymal lung disease; however, this study does demonstrate for the first time a potential role for the bSSFP sequence as an alternative radiation-free noncontrast imaging modality for use in patients with pulmonary fibrosis.

CT features of pulmonary arterial hypertension and its major subtypes: a systematic CT evaluation of 292 patients from the ASPIRE Registry

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.