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.

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.

Do Hemodynamic Definitions of Chronic Thromboembolic Pulmonary Hypertension Distinguish Between Distinct Phenotypes of Chronic Thromboembolic Pulmonary Disease?

BACKGROUND: Chronic thromboembolic pulmonary disease (CTEPD) is defined by chronic organized thrombi in the pulmonary circulation without or with pulmonary hypertension (CTEPH). The current definition of CTEPH has adopted lower mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) thresholds. Our aim was to identify its impact on the characterization of patients with CTEPD. METHODS: All consecutive CTEPD patients referred for cardiopulmonary exercise testing (CPET) in a PH center were divided into four groups based on pulmonary haemodynamics. Group A: mPAP≤20 mmHg, Group B: mPAP>20 mmHg with PVR>2 and ≤3 WU, Group C: mPAP>20 mmHg with PVR>3 WU, Group D: mPAP>20 mmHg with PVR<2 WU (''unclassified''). We compared CPET, CT pulmonary angiography, and MRI data across the groups. RESULTS: There was mild aerobic capacity impairment, mild/moderate ventilatory inefficiency, and no significant cardiac limitation on CPET in all groups. However, patients in Groups A and D had better ventilatory efficiency and less oxygen desaturation on exercise due to lower dead-space ventilation. There was no difference in chronic pulmonary emboli burden and distribution, or resting RV function between the groups. Seventeen patients were reclassified as having ''CTEPH'' based on the current definition. No functional deterioration was noted within a median period of 13 months on repeat CPET. CONCLUSIONS: CTEPD patients with similar clot burden and RV function without or with mild/moderate PH displayed a similar pattern of cardiopulmonary limitation, except for ventilatory efficiency. The current definition for CTEPH may lead to reclassification of CTEPH in a considerable number of patients.

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.

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.

Incremental Shuttle Walking Test Distance Is Reduced in Patients With Pulmonary Hypertension in World Health Organisation Functional Class I.

Background: There is increasing interest in screening for and diagnosing pulmonary hypertension earlier in the course of disease. However, there is limited data on cardiopulmonary abnormalities in patients with pulmonary hypertension newly diagnosed in World Health Organization Function Class (WHO FC) I. Methods: Data were retrieved from the ASPIRE registry (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral center) for consecutive treatment naïve patients diagnosed with pulmonary hypertension by cardiac catheterization between 2001 and 2010 who underwent incremental shuttle walk exercise testing. Results: Eight hundred and ninety-five patients were diagnosed with Group 1-5 pulmonary hypertension. Despite the absence of symptoms, patients in WHO FC I (n = 9) had a significant reduction in exercise capacity (Incremental shuttle walk distance percent predicted (ISWD%pred) 65 ± 13%, Z score -1.77 ± 1.05), and modest pulmonary hypertension with a median (interquartile range) pulmonary artery pressure 31(20) mmHg and pulmonary vascular resistance 2.1(8.2) Wood Units, despite a normal diffusion of carbon monoxide adjusted for age and sex (DLco)%pred 99 ± 40%. Compared to patients in WHO FC I, patients in WHO FC II (n = 162) had a lower ISWD%pred 43 ± 22 and lower DLco%pred 65 ± 21%. Conclusion: Our results demonstrate that patients with newly diagnosed pulmonary hypertension with no or minimal symptomatic limitation have a significant reduction of exercise capacity.

Incremental shuttle walk test distance and autonomic dysfunction predict survival in pulmonary arterial hypertension.

BACKGROUND: To ensure effective monitoring of pulmonary arterial hypertension (PAH), a simple, reliable assessment of exercise capacity applicable over a range of disease severity is needed. The aim of this study was to assess the ability of the incremental shuttle walk test (ISWT) to correlate with disease severity, measure sensitivity to change, and predict survival in PAH. METHODS: We enrolled 418 treatment-naïve patients with PAH with baseline ISWT within 3 months of cardiac catheterization. Clinical validity and prognostic value of ISWT distance were assessed at baseline and 1 year. RESULTS: ISWT distance was found to correlate at baseline with World Health Organization functional class, Borg score, and hemodynamics without a ceiling effect (all p < 0.001). Walking distance at baseline and after treatment predicted survival; the area under the receiver operating characteristic curve for ability of ISWT distance to predict mortality was 0.655 (95% confidence interval 0.553-0.757; p = 0.004) at baseline and 0.737 (95% confidence interval 0.643-0.827; p < 0.001) at 1 year after initiation of treatment. Change in ISWT distance also predicted survival (p = 0.04). Heart rate (HR) and systolic blood pressure (SBP) parameters reflecting autonomic response to exercise (highest HR, change in HR, HR recovery at 1 minute >18 beats/min, highest SBP, change in SBP, and 3-minute SBP ratio) were significant predictors of survival (all p < 0.05). CONCLUSIONS: In patients with PAH, the ISWT is simple to perform, allows assessment of maximal exercise capacity, is sensitive to treatment effect, predicts outcome, and has no ceiling effect. Also, measures of autonomic function made post-exercise predict survival in PAH.