Identification of cardiac MRI 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 (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

Incremental Shuttle Walking 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 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

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

Pulmonary hypertension (PH) is classified into 5 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 3 months of cardiac catheterization. Patients were stratified according to incremental shuttle walk test distance (ISWD) and ISWT distance percent predicted (ISWD%pred). 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 1 year were all significant predictors of outcome. In patients with non-Group 1 PH the Incremental Shuttle Walk Test 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

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 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 utility in risk stratification in pulmonary arterial hypertension (PAH). Methods: Consecutive patients with pulmonary hypertension were identified from the ASPIRE registry (2001-2018). Thresholds for levels of risk were identified at baseline, tested at follow-up and incorporation into current risk stratification approaches assessed. Results: Of 4524 treatment-naïve patients with pulmonary hypertension who underwent maximal exercise testing 1,847 patients had PAH. A step-wise reduction in one-year-mortality was seen between levels 1 (≤30m; 32% mortality) and 7 (340-420m; 1% mortality) with no mortality for levels 8-12 (≥430m) in idiopathic and connective tissue disease related PAH. Thresholds derived at baseline of ≤180m (>10%; high-risk), 190-330m (5-10%; intermediate-risk) and ≥340m (<5%; low-risk of one-year mortality) were applied at follow-up and also accurately identified levels of risk. Thresholds were incorporated into the REVEAL 2.0 risk score calculator and French low-risk approach to risk stratification and distinct categories of risk remained. Conclusion: 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-walk-test, combining some of the advantages of maximal exercise testing whilst maintaining the simplicity of a simple to perform field test

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