Systematic pulmonary embolism follow-up increases diagnostic rates of chronic thromboembolic pulmonary hypertension and identifies less severe disease: results from the ASPIRE Registry.

BACKGROUND: Diagnostic rates and risk factors for the subsequent development of chronic thromboembolic pulmonary hypertension (CTEPH) following pulmonary embolism (PE) are not well defined. METHODS: Over a 10-year period (2010-2020), consecutive patients attending a PE follow-up clinic in Sheffield, UK (population 554 600) and all patients diagnosed with CTEPH at a pulmonary hypertension (PH) referral centre in Sheffield (referral population estimated 15-20 million) were included. RESULTS: Of 1956 patients attending the Sheffield PE clinic 3 months following a diagnosis of acute PE, 41 were diagnosed with CTEPH with a cumulative incidence of 2.10%, with 1.89% diagnosed within 2 years. Of 809 patients presenting with pulmonary hypertension (PH) and diagnosed with CTEPH, 32 were Sheffield residents and 777 were non-Sheffield residents. Patients diagnosed with CTEPH at the PE follow-up clinic had shorter symptom duration (p<0.01), better exercise capacity (p<0.05) and less severe pulmonary haemodynamics (p<0.01) compared with patients referred with suspected PH. Patients with no major transient risk factors present at the time of acute PE had a significantly higher risk of CTEPH compared with patients with major transient risk factors (OR 3.6, 95% CI 1.11-11.91; p=0.03). The presence of three computed tomography (CT) features of PH in combination with two or more out of four features of chronic thromboembolic pulmonary disease at the index PE was found in 19% of patients who developed CTEPH and in 0% of patients who did not. Diagnostic rates and pulmonary endarterectomy (PEA) rates were higher at 13.2 and 3.6 per million per year, respectively, for Sheffield residents compared with 3.9-5.2 and 1.7-2.3 per million per year, respectively, for non-Sheffield residents. CONCLUSIONS: In the real-world setting a dedicated PE follow-up pathway identifies patients with less severe CTEPH and increases population-based CTEPH diagnostic and PEA rates. At the time of acute PE diagnosis the absence of major transient risk factors, CT features of PH and chronic thromboembolism are risk factors for a subsequent diagnosis of CTEPH.

Identification of Cardiac Magnetic Resonance Imaging Thresholds for Risk Stratification in Pulmonary Arterial Hypertension.

Rationale: Pulmonary arterial hypertension (PAH) is a life-shortening condition. The European Society of Cardiology and European Respiratory Society and the REVEAL (North American Registry to Evaluate Early and Long-Term PAH Disease Management) risk score calculator (REVEAL 2.0) identify thresholds to predict 1-year mortality.Objectives: This study evaluates whether cardiac magnetic resonance imaging (MRI) thresholds can be identified and used to aid risk stratification and facilitate decision-making.Methods: Consecutive patients with PAH (n = 438) undergoing cardiac MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Center) MRI database. Thresholds were identified from a discovery cohort and evaluated in a test cohort.Measurements and Main Results: A percentage-predicted right ventricular end-systolic volume index threshold of 227% or a left ventricular end-diastolic volume index of 58 ml/m2 identified patients at low (<5%) and high (>10%) risk of 1-year mortality. These metrics respectively identified 63% and 34% of patients as low risk. Right ventricular ejection fraction >54%, 37-54%, and <37% identified 21%, 43%, and 36% of patients at low, intermediate, and high risk, respectively, of 1-year mortality. At follow-up cardiac MRI, patients who improved to or were maintained in a low-risk group had a 1-year mortality <5%. Percentage-predicted right ventricular end-systolic volume index independently predicted outcome and, when used in conjunction with the REVEAL 2.0 risk score calculator or a modified French Pulmonary Hypertension Registry approach, improved risk stratification for 1-year mortality.Conclusions: Cardiac MRI can be used to risk stratify patients with PAH using a threshold approach. Percentage-predicted right ventricular end-systolic volume index can identify a high percentage of patients at low-risk of 1-year mortality and, when used in conjunction with current risk stratification approaches, can improve risk stratification. This study supports further evaluation of cardiac MRI in risk stratification in PAH.

Mild parenchymal lung disease and/or low diffusion capacity impacts survival and treatment response in patients diagnosed with idiopathic pulmonary arterial hypertension.

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<0.0001). In the combined group of IPAHno-LD and IPAHmild-LD, independent predictors of higher mortality were increasing age, lower diffusing capacity of the lung for carbon monoxide (D LCO), lower exercise capacity and a diagnosis of IPAHmild-LD (all p<0.05). Exercise capacity and quality of life improved (both p<0.0001) following treatment in patients with IPAHno-LD, but not IPAHmild-LD A proportion of patients with IPAHno-LD had a D LCO <45%; these patients had poorer survival than patients with D LCO ≥45%, although they demonstrated improved exercise capacity following treatment.The presence of even mild parenchymal lung disease in patients who would be classified as IPAH according to current recommendations has a significant adverse effect on outcomes. This phenotype can be identified using lung function testing and clinical CT reports. Patients with IPAH, no lung disease and severely reduced D LCO may represent a further distinct phenotype. These data suggest that randomised controlled trials of targeted therapies in patients with these phenotypes are required.

Partial anomalous pulmonary venous drainage in patients presenting with suspected pulmonary hypertension: A series of 90 patients from the ASPIRE registry.

BACKGROUND AND OBJECTIVE: There are limited data regarding patients with PAPVD with suspected and diagnosed PH. METHODS: Patients with PAPVD presenting to a large PH referral centre during 2007-2017 were identified from the ASPIRE registry. RESULTS: 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 < 0.05). Sixty-five patients were diagnosed with PH (defined as mPAP ≥ 25 mm Hg), which was post-capillary in 24 (37%). No additional causes of PH were identified in 28 patients; 17 of these (26% of those patients with PH) had a PVR > 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. CONCLUSION: 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.

The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension.

Pulmonary endarterectomy (PEA) is the gold standard treatment for operable chronic thromboembolic pulmonary hypertension (CTEPH). However, a proportion of patients with operable disease decline surgery. There are currently no published data on this patient group. The aim of this study was to identify outcomes and prognostic factors in a large cohort of consecutive patients with CTEPH.Data were collected for consecutive, treatment-naive CTEPH patients at the Pulmonary Vascular Disease Unit of the Royal Hallamshire Hospital (Sheffield, UK) between 2001 and 2014.Of 550 CTEPH patients (mean±sd age 63±15 years, follow-up 4±3 years), 49% underwent surgery, 32% had technically operable disease and did not undergo surgery (including patient choice n=72 and unfit for surgery n=63), and 19% had inoperable disease due to disease distribution. The 5-year survival was superior in patients undergoing PEA (83%) versus technically operable disease who did not undergo surgery (53%) and inoperable due to disease distribution (59%) (p<0.001). Survival was superior in patients following PEA compared with those offered but declining surgery (55%) (p<0.001). In patients offered PEA, independent prognostic factors included mixed venous oxygen saturation, gas transfer and patient decision to proceed to surgery.Outcomes in CTEPH following PEA are excellent and superior to patients declining surgery, and strongly favour consideration of a surgical intervention in eligible patients.

Long-term outcomes of domiciliary intravenous iloprost in idiopathic and connective tissue disease-associated pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: There are few published data on the efficacy of i.v. iloprost in pulmonary arterial hypertension (PAH). We present long-term outcomes in PAH patients receiving i.v. iloprost in a large UK referral centre. METHODS: Eighty patients with idiopathic PAH (iPAH, n = 46) or PAH associated with connective tissue disease (CTD-PAH, n = 34) were identified as receiving domiciliary i.v. iloprost between January 1999 and April 2015. Baseline characteristics, doses achieved, functional class at follow-up and survival data were retrieved from hospital databases. RESULTS: Median maximum dose achieved was 4.6 ng/kg/min in the iPAH group and 5.0 ng/kg/min in CTD-PAH patients. Exercise capacity significantly improved in the first 6 months of therapy in IPAH patients. Overall 1-, 3- and 5-year survival was 78%, 64% and 52% in iPAH (P = 0.002) and 64%, 26% and 21% in CTD-PAH. Independent predictors of survival were age and exercise capacity. CONCLUSION: We report improved survival to that previously reported in iPAH patients treated with domiciliary i.v. iloprost. This may be in part related to higher administered doses. Patients with CTD-PAH had poorer survival, reinforcing the need for early transplantation referral in suitable patients.

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.

Pericardial actinomycosis.

A man in his 50s, with a history of night sweats and weight loss, presented acutely with dyspnoea and chest pain. Imaging revealed right middle lobe consolidation and a large pericardial effusion. The diagnosis of actinomycosis was made using endobronchial ultrasound-guided sampling from the pericardial effusion. An orthopantomogram demonstrated that the source was a large cavity in the left lower wisdom tooth. This tooth was extracted before the completion of his antibiotic course, and the patient made a full recovery. Cardiac actinomycosis is rare, and there are few case reports describing endobronchial ultrasound-guided sampling of pericardial fluid.

Pulmonary Hypertension: Intensification and Personalization of Combination Rx (PHoenix): A phase IV randomized trial for the evaluation of dose-response and clinical efficacy of riociguat and selexipag using implanted technologies.

Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital-based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory-approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 × 2 randomized crossover trial, patients with PAH established on guideline-recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory-approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra-patient efficacy of the two treatment approaches.

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.

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.

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.

Black blood MRI has diagnostic and prognostic value in the assessment of patients with pulmonary hypertension.

OBJECTIVES: 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). METHODS: 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. RESULTS: PFA >1 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). CONCLUSIONS: PFA scoring is of diagnostic and prognostic value in the assessment of patients with suspected PH. and is a predictor of mortality. KEY POINTS: • 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.

Diagnostic accuracy of contrast-enhanced MR angiography and unenhanced proton MR imaging compared with CT pulmonary angiography in chronic thromboembolic pulmonary hypertension.

OBJECTIVE: To evaluate the diagnostic accuracy of contrast-enhanced MR angiography (CE-MRA) and the added benefit of unenhanced proton MR angiography compared with CT pulmonary angiography (CTPA) in patients with chronic thromboembolic disease (CTE). METHODS: A 2 year retrospective study of 53 patients with chronic thromboembolic pulmonary hypertension who underwent CTPA and MRI for suspected pulmonary hypertension and a control group of 36 patients with no CT evidence of pulmonary embolism. The MRI was evaluated for CTE and the combined diagnostic accuracy of ce-MRA and unenhanced proton MRA was determined. CE-MRA generated lung perfusion maps were also assessed. RESULTS: The overall sensitivity and specificity of CE-MRA in diagnosing proximal and distal CTE were 98% and 94%, respectively. The sensitivity improved from 50% to 88% for central vessel disease when CE-MRA images were analysed with unenhanced proton MRA. The CE-MRA identified more stenoses (29/18), post-stenosis dilatation (23/7) and occlusions (37/29) compared with CTPA. The CE-MRA perfusion images showed a sensitivity of 92% for diagnosing CTE. CONCLUSION: CE-MRA has high sensitivity and specificity for diagnosing CTE. The sensitivity of CE-MRA for visualisation of adherent central and lobar thrombus significantly improves with the addition of unenhanced proton MRA which delineates the vessel wall.

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.

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 48 hours. 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.

10,589 CT pulmonary angiograms: evaluating the yield of acute pulmonary embolism.

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

CT pulmonary angiography combined with echocardiography in suspected systemic sclerosis-associated pulmonary arterial hypertension.

OBJECTIVE: 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. METHODS: 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). RESULTS: 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 both <0.001). 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. CONCLUSION: 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.

Maximal Exercise Testing Using the Incremental Shuttle Walking Test Can Be Used to Risk-Stratify Patients with Pulmonary Arterial Hypertension.

Rationale: Exercise capacity predicts mortality in pulmonary arterial hypertension (PAH), but limited data exist on the routine use of maximal exercise testing.Objectives: This study evaluates a simple-to-perform maximal test (the incremental shuttle walking test) and its use in risk stratification in PAH.Methods: Consecutive patients with pulmonary hypertension were identified from the ASPIRE (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) registry (2001-2018). Thresholds for levels of risk were identified at baseline and tested at follow-up, and their incorporation into current risk stratification approaches was assessed.Results: Of 4,524 treatment-naive patients with pulmonary hypertension who underwent maximal exercise testing, 1,847 patients had PAH. A stepwise reduction in 1-year mortality was seen between levels 1 (≤30 m; 32% mortality) and 7 (340-420 m; 1% mortality) with no mortality for levels 8-12 (≥430 m) in idiopathic and connective tissue disease-related PAH. Thresholds derived at baseline of ≤180 m (>10%; high risk), 190-330 m (5-10%; intermediate risk), and ≥340 m (<5%; low risk of 1-yr mortality) were applied at follow-up and also accurately identified levels of risk. Thresholds were incorporated into the REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management) 2.0 risk score calculator and French low-risk approach to risk stratification, and distinct categories of risk remained.Conclusions: We have demonstrated that maximal exercise testing in PAH stratifies mortality risk at baseline and follow-up. This study highlights the potential value of the incremental shuttle walking test as an alternative to the 6-minute walking test, combining some of the advantages of maximal exercise testing and maintaining the simplicity of a simple-to-perform field test.

The incremental shuttle walk test predicts mortality in non-group 1 pulmonary hypertension: results from the ASPIRE Registry.

Pulmonary hypertension (PH) is classified into five groups based on disease etiology but there is only limited information on the prognostic value of exercise testing in non-group 1 PH. In group 1 PH, the incremental shuttle walking test (ISWT) distance has been shown to correlate with pulmonary hemodynamics and predict survival without a ceiling effect. This study assessed the ISWT in non-group 1 PH. Data were retrieved from the ASPIRE Registry (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) for consecutive patients diagnosed with PH. Patients were required to have been systematically assessed as group 2-5 PH and to have a baseline ISWT within three months of cardiac catheterization. Patients were stratified according to incremental shuttle walk test distance (ISWD) and ISWT distance percent predicted (ISWD%pred). A total of 479 patients with non-group 1 PH were identified. ISWD and ISWD%pred correlated significantly with symptoms and hemodynamic severity. ISWD and ISWD%pred predicted survival with no ceiling effect. The test was prognostic in groups 2, 3, and 4. ISWD and ISWD%pred and change in ISWD and ISWD%pred at one year were all significant predictors of outcome. In patients with non-group 1 PH the ISWT is a simple non-invasive test that is easy to perform, is predictive of survival at baseline and follow-up, reflects change, and can be used in the assessment of PH of any etiology.