Hendrik W. van Es’s research while affiliated with St. Antonius Ziekenhuis and other places

Screening for obstructive coronary artery disease (CAD) with coronary computed tomography angiography (CCTA) could prevent unnecessary invasive coronary angiography (ICA) procedures during work-up for trans-catheter aortic valve implantation (TAVI). CT-derived fractional flow reserve (CT-FFR) improves CCTA accuracy in chest pain patients. However, its reliability in the TAVI population is unknown. This systematic review and meta-analysis assesses CCTA and CT-FFR in TAVI candidates. PubMed, Embase and Web of Science were searched for studies regarding CCTA and/or CT-FFR in TAVI candidates. Primary endpoint was correct identification and rule-out of obstructive CAD. Results were pooled in a meta-analysis. Thirty-four articles were part of the meta-analysis, reporting results for CCTA and CT-FFR in 7235 and 1269 patients, respectively. Reference standard was mostly anatomical severity of CAD. At patient level, pooled CCTA sensitivity was 94.0% and specificity 72.4%. CT-FFR sensitivity was 93.2% and specificity 70.3% with substantial variation between studies. However, in studies that compared both, CT-FFR performed better than CCTA. Sensitivity of CCTA versus CT-FFR was 74.9% versus 83.9%, and specificity was 65.5% versus 89.8%. Negative CCTA accurately rules out CAD in the TAVI population. CCTA could lead to significant reduction in pre-TAVI ICA, but false positives remain high. Diagnostic accuracy of CT-FFR was comparable to that of CCTA in our meta-analyses, but in studies performing a direct comparison, CT-FFR performed better than CCTA. However, as most studies were small and used CT-FFR software exclusively available for research, a large study on CT-FFR in TAVI work-up using commercially available CT-FFR software would be appropriate before considering routine implementation. Question Coronary artery disease (CAD) screening with invasive coronary angiography before trans-catheter aortic valve implantation (TAVI) is often retrospectively unnecessary, revealing no obstructive CAD. Findings Coronary CTA ruled out CAD in approximately half of TAVI candidates. CT-derived fractional flow reserve (CT-FFR) performed similarly overall but better than coronary CTA in direct comparison. Clinical relevance Addition of coronary CTA to TAVI planning-CT to screen for obstructive CAD could reduce negative invasive coronary angiographies in TAVI work-up. CT-FFR could reduce false-positive coronary CTA results, improving its gatekeeper function in this population, but more data is necessary.

Introduction Early detection of cardiac sarcoidosis (CS) is crucial due to its association with severe complications such as ventricular arrhythmias, heart failure, and sudden cardiac death. Advanced imaging techniques like cardiac magnetic resonance imaging (CMR) and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) are effective in detecting CS but not easily accessible. The optimal method for selecting patients for advanced screening remains uncertain. Methods In this retrospective cohort study, all extracardiac sarcoidosis patients screened for CS were reviewed. CS was defined as a multidisciplinary team (MDT) consensus diagnosis. Univariate and multivariate binary logistic regressions were used to identify factors associated with CS, assessing their diagnostic performance, and integrating them into a diagnostic model. Results Out of 354 patients (average age 51.5 years, 52.5% male), 18.4% were diagnosed with CS. In our cohort, male gender, a QRS duration > 120 ms, and nsVT on Holter monitoring were identified as significant markers associated with CS. Combining age, gender, AV-block or QRS > 120ms on ECG, and nsVT on Holter monitoring provided the highest diagnostic accuracy (AUC of 0.82). Cardiac biomarkers NT-proBNP and troponin T did not improve the diagnostic performance. Conclusion In our cohort, male gender, a QRS duration > 120 ms, and nsVT on Holter monitoring were identified as significant markers associated with the presence of cardiac sarcoidosis. These clinical markers may aid in selecting sarcoidosis patients for screening with advanced cardiac imaging, potentially leading to earlier detection and management of the disease.

Objectives To perform a systematic review and meta-analysis on diagnostic accuracy and other outcomes of coronary computed tomography angiography (CCTA) and CT-derived fractional flow reserve (CT-FFR) in candidates for trans-catheter aortic valve implantation (TAVI). Background Screening for obstructive coronary artery disease (CAD) with CCTA during TAVI work-up could prevent unnecessary invasive coronary angiography (ICA). This becomes increasingly relevant as the TAVI-population grows. CT-FFR improves CCTA accuracy in chest pain patients, but its reliability is unknown in the TAVI-population. Methods Pubmed, Embase and Web of Science were searched for studies regarding CCTA and/or CT-FFR in TAVI-candidates. Primary endpoint was correct identification and rule-out of obstructive CAD. Results were pooled in a meta-analysis. Results Twenty-four of the 29 included articles were part of the meta-analysis, reporting results for CCTA and CT-FFR in 3.494 and 797 patients respectively. Reference standard was anatomical severity of CAD in most studies. At patient-level, pooled CCTA sensitivity was 94.3% and specificity 74.8%. CT-FFR sensitivity was 91.5% and specificity 60.3% with strong variation between studies. CCTA correctly ruled out CAD in 52% of all patients, but 42% of positive CCTAs were false positives. CT-FFR correctly ruled out CAD in 47% of all patients included in this meta-analysis, but showed better accuracy than CCTA in studies that compared both. In these studies, sensitivity of CCTA versus CT-FFR was 70.7% versus 79.0% and specificity was 64.4% versus 92.9%. Conclusions Negative CCTA effectively rules-out CAD in the TAVI-population. Adding CCTA to TAVI work-up could lead to significant reduction in pre-TAVI ICA procedures, but the proportion of false-positives remains high. In studies performing a direct comparison, CT-FFR performed better than CCTA. This is not reflected in the CT-FFR meta-analysis. Therefore, diagnostic accuracy of CT-FFR and added value over CCTA in the TAVI-population remains unclear. Further research regarding validation and reliability is warranted.Meta-analysis of CCTA and CT-FFR

Computed tomography-derived fractional flow reserve (CT-FFR) enhances the specificity of coronary computed tomography angiography (CCTA) to that of the most specific non-invasive imaging techniques, while maintaining high sensitivity in stable coronary artery disease (CAD). As gatekeeper for invasive coronary angiography (ICA), use of CT-FFR results in a significant reduction of negative ICA procedures and associated costs and complications, without increasing cardiovascular events. It is expected that CT-FFR algorithms will continue to improve, regarding accuracy and generalisability, and that introduction of new features will allow further treatment guidance and reduced invasive diagnostic testing. Advancements in CCTA quality and artificial intelligence (AI) are starting to unfold the incremental diagnostic and prognostic capabilities of CCTA’s attenuation-based images in CAD, with future perspectives promising additional CCTA parameters which will enable non-invasive assessment of myocardial ischaemia as well as CAD activity and future cardiovascular risk. This review discusses practical application, interpretation and impact of CT-FFR on patient care, and how this ties into the CCTA ‘one stop shop’ for coronary assessment and patient prognosis. In this light, selective adoption of the most promising, objective and reproducible techniques and algorithms will yield maximal diagnostic value of CCTA without overcomplicating patient management and guideline recommendations.

Background Idiopathic pulmonary fibrosis (IPF) with co-existent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts. Methods Visual emphysema presence (>0% emphysema) scored on computed tomography identified CPFE patients (CPFE:non-CPFE: derivation cohort=317:183; replication cohort=358:152), who were subgrouped using 10%, or 15% visual emphysema thresholds, and an unsupervised machine learning model considering emphysema and ILD extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide (DLco) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups. Results In both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baseline DLco compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year DLco decline showed stronger mortality associations than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials and in subjects subgrouped by ≥15% emphysema and using unsupervised machine learning. Importantly, the unsupervised machine learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines ≥5% and ≥10% showed strong mortality associations. Conclusion When assessing disease progression in IPF, DLco decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.

Background Progressive pulmonary fibrosis (PPF) is characterized by deterioration of respiratory symptoms, lung function decline and progressive fibrosis on high-resolution computed tomography (HRCT). It is associated with poor prognosis. Patients with connective tissue disease-related interstitial lung disease (CTD-ILD) may also develop PPF and need intensified clinical management. However, different criteria for PPF are used in trials (i.e. INBUILD and RELIEF) and the ATS/ERS/JRS/ALAT 2022 guideline. [1-3] This variety in criteria complicates study comparison and clinical implication. Objectives To explore the prognostic relevance for mortality of different PPF criteria in patients with CTD-ILD. Methods This is a single center retrospective cohort study in patients with CTD-ILD or interstitial pneumonia with autoimmune features between 2005 and 2021. The prognostic relevance was compared between the INBUILD criteria [1] , the ATS/ERS/JRS/ALAT 2022 criteria [3] , and the simplified progressive fibrosing (simplified PF) criteria used in a previous cohort (≥10% relative decline in FVC, ≥15% relative decline in DLCO, or progression of fibrosis on HRCT within two years) [4] in the time-dependent receiver operator characteristic model. Results The cohort consisted of 230 patients. The median age was 63 years (IQR 54—69), and 122 (53%) were female. The most prevalent CTD was rheumatoid arthritis (n=77, 33%), followed by 38 (17%) patients with idiopathic inflammatory myopathies and 33 (14%) with primary Sjögren’s syndrome. Various HRCT patterns were observed at baseline: UIP in 63 (27%) patients, fibrotic NSIP in 21 (9%), cellular NSIP in 25 (11%), mixed NSIP in 79 (34%), OP in 34 (15%), two (1%) mixed NSIP/OP, and other patterns in six. The median follow-up period was 6 (3—9) years. Mortality risk was independently associated with age (adjusted HR 1.07, p < 0.001), smoking history (adjusted HR 1.90, p = 0.045), extent of fibrosis on HRCT at baseline (adjusted HR 1.05, p = 0.018) and baseline DLCO % of predicted (adjusted HR 0.97, p = 0.013). PPF was observed in 61 (27%) patients meeting INBUILD criteria, 53 (23%) meeting ATS/ERS/JRS/ALAT 2022 criteria, 136 (59%) meeting simplified PF criteria and 125 (54%) when using simplified PF criteria with a threshold for HRCT ≥ 5% increase in the extent of fibrosis. The prognostic relevance for mortality did not differ between simplified PF criteria, INBUILD and ATS/ERS/JRS/ALAT 2022 criteria; the prognostic relevance improved when the simplified PF criteria defined HRCT progression with a ≥5% increase in fibrosis. (Figure 1) Conclusion Higher age, smoking, increased extent of fibrosis and low baseline DLCO were associated with poor prognosis. The prognostic value was similar between the different PPF criteria and increased during the first three years and achieved a plateau thereafter. References [1]KR Flaherty, AU Wells, V Cottin, et al. N Engl J Med. 2019;381(18):1718-27. [2]J Behr, A Prasse, M Kreuter, et al. Lancet Respir Med. 2021;9(5):476-86. [3]G Raghu, M Remy-Jardin, L Richeldi, et al. Am J Respir Crit Care Med. 2022;205(9):e18-e47. [4]YH Chiu, J Spierings, PA de Jong, et al. Respir Med. 2021;187:106579. Figure 1. Acknowledgements NIL. Disclosure of Interests Yu-Hsiang Chiu: None declared, Maaike Koops: None declared, Mareye Voortman: None declared, H. Wouter van Es: None declared, Lucianne Langezaal: None declared, Paco Welsing: None declared, Anna Jamnitski: None declared, Anne Wind: None declared, Jacob M. van Laar Grant/research support from: Grant from Boehringer, Astra Zeneca, MSD, Roche, J.C. Grutters: None declared, Julia Spierings Grant/research support from: A grant from Boehringer.

Background: Idiopathic pulmonary fibrosis (IPF) with co-existent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may be associated with reduced FVC decline compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts. Methods: Visual emphysema extent (CPFE:non-CPFE: derivation cohort=317:183; replication cohort=358:152), scored on computed tomography imaging subgrouped CPFE patients using either a) 10%, or b) 15% visual emphysema threshold, or c) an unsupervised machine learning model considering emphysema and ILD extents. Baseline characteristics, 1-year forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLco) decline (linear mixed effects models), and their associations with mortality (multivariable Cox regression models) were compared across CPFE and non-CPFE subgroups. Results: In both IPF cohorts, CPFE patients with >10% emphysema had a greater smoking history and lower baseline DLco compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with >10% emphysema, 1-year DLco decline was a better indicator of mortality than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials. Results were replicated in the >15% emphysema population and using unsupervised machine learning. Importantly, the unsupervised machine learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines >5% and >10% showed comparable mortality associations. Conclusion: When assessing disease progression in IPF, DLco decline should be considered in patients with >10% emphysema and a >5% 1-year FVC decline threshold considered in non-CPFE IPF patients.

Background: Connective tissue diseases-associated interstitial lung disease (CTD-ILD) is a heterogeneous condition that impairs quality of life and is associated with premature death. Progressive pulmonary fibrosis (PPF) has been identified as an important risk factor for poor prognosis. However, different criteria for PPF are used in clinical studies, which may complicate comparison between trials and translation of study findings into clinical practice. Methods: This is a retrospective single center study in patients with CTD-ILD. The prognostic relevance of PPF definitions, including INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified progressive fibrosing (simplified PF) criteria, were examined in this cohort and validated in the other reported Dutch CTD-ILD cohort. Results: A total of 230 patients with CTD-ILD were included and the median follow-up period was six (3-9) years. Mortality risk was independently associated with age (adjusted HR 1.07, p < 0.001), smoking history (adjusted HR 1.90, p = 0.045), extent of fibrosis on high-resolution computed tomography (HRCT) at baseline (adjusted HR 1.05, p = 0.018) and baseline DLCO (adjusted HR 0.97, p = 0.013). Patients with regular pulmonary function tests in the first 2 years (adjusted HR 0.42, p = 0.002) had a better survival. The prognostic relevance for survival was similar between the three PPF criteria in the two cohorts. Conclusion: Higher age, smoking, increased extent of fibrosis and low baseline DLCO were associated with poor prognosis, while regular pulmonary function evaluation was associated with better survival. The INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified PF criteria revealed similar prognostication.

Background Computer quantification of baseline computed tomography (CT) radiologic pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP). Methods Two CT scans 6–36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiologic PPFE-like lesions (Δ-PPFE) was calculated. Δ-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Δ-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, gender, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change. Findings Δ-PPFE associated weakly with ILD and FVC change. 22–26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (HR=1.25, 95% CI 1.16–1.34, p<0.0001) and the FHP cohort (HR=1.16, 95% CI 1.00–1.35, p=0.045). Interpretation Progression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression.