BACKGROUND:Despite a significant association of atherogenic index of plasma (AIP) with plasma atherogenicity as well as insulin resistance and new onset of diabetes, data on the risk of rapid plaque progression (RPP) of major epicardial coronary arteries related to AIP according to established diabetes is limited. METHODS:This study evaluated the association between AIP and RPP according to diabetes in 1485 adults (60.9 ​± ​9.2 years, 58.9% men, 23.8% diabetes) using serial coronary computed tomography angiography. AIP was defined as the base 10 logarithm of the ratio of triglycerides to high-density lipoprotein cholesterol (mmol/L). RPP was defined as a change in percent atheroma volume (PAV) ≥1.0%/year. RESULTS:During a median follow-up of 3.4 years, the incidence of RPP was 26.1%. Compared with non-diabetic subjects, diabetic subjects exhibited significantly higher AIP levels, larger baseline plaque burden, and higher RPP incidence. After adjusting for age, sex, hypertension, overweight or obesity, current smoking, low-density lipoprotein cholesterol and creatinine levels, baseline total PAV, and the use of aspirin, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or statins, AIP (per 0.1-unit increase) was associated with the risk of RPP in non-diabetic subjects (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.13; p ​< ​0.05) but not in diabetic subjects (OR 1.04, 95% CI 0.95-1.14; p ​= ​0.430). CONCLUSION:AIP is independently associated with the risk of RPP in the absence of established diabetes. This finding suggests that AIP may be an effective biomarker for predicting RPP in the population of non-diabetic adults. TRIAL REGISTRATION:ClinicalTrials.govNCT02803411.

BACKGROUND:Complete revascularisation has been associated with improved short-term outcomes in patients with coronary artery disease, but whether these benefits persist long-term and can be defined non-invasively remains uncertain. We investigated the long-term prognostic impact of complete versus incomplete revascularisation determined by coronary CT angiography-derived fractional flow reserve (FFRCT). METHODS:In this prospective multicentre study, 900 patients with new-onset stable angina and at least one coronary stenosis of 30% or greater on coronary CT angiography were followed for a median of 7 years. FFRCT values were obtained for each vessel, and patients were categorised as completely revascularised (all vessels with FFRCT ≤0.80 revascularised), incompletely revascularised (one or more vessels with FFRCT ≤0.80 not revascularised), or with normal physiology (all vessels with FFRCT >0.80). Early revascularisation was defined as treatment within 90 days of the index scan. Quantitative coronary plaque burden was assessed using artificial intelligence-enabled plaque analysis. The primary endpoint was a composite of cardiovascular death or spontaneous myocardial infarction. RESULTS:Of 900 patients, 210 (23%) were classified as incompletely revascularised, 167 (19%) as completely revascularised and 523 (58%) as having normal physiology. The primary endpoint occurred in 34 of 210 (16.2%) incompletely revascularised patients, 13 of 167 (7.8%) completely revascularised patients and 30 of 523 (5.7%) with normal physiology. Incomplete revascularisation was associated with higher risk compared with complete revascularisation (HR 2.33, 95% CI 1.23 to 4.42; p=0.01) and normal physiology (HR 3.54, 95% CI 2.16 to 5.81; p<0.001). These associations remained significant after adjustment for total plaque burden, and the risk difference persisted beyond 3 years of follow-up. CONCLUSION:Complete revascularisation defined by CT-derived fractional flow reserve was associated with a sustained reduction in cardiovascular death and spontaneous myocardial infarction over 7 years, supporting its potential role as a non-invasive tool to guide revascularisation strategies in stable coronary artery disease.

BACKGROUND:The growing popularity of cannabis smoking in an era of legalisation has prompted concerns about respiratory health. OBJECTIVE:To investigate clinical and airway epithelial transcriptomic features associated with cannabis smoking. METHODS:This cross-sectional study analysed data from 139 cannabis-smoking participants categorised by joint-year exposure (low: ≤5; moderate: >5-20; high: >20 joint-years) and 57 never-smokers. We evaluated respiratory symptom questionnaire scores, lung function measurements, chest computed tomography and hyperpolarised 129Xenon pulmonary magnetic resonance imaging measurements across groups. We compared the expression of immune response signatures and mucin genes in airway epithelial brushings collected from bronchoscopy. Using air-liquid interface cell cultures, we quantified epithelial mucin 5AC (MUC5AC) protein and correlated its expression with clinical outcomes. RESULTS:Among cannabis-smoking participants (48% male, median age of 27 years), 84% reported current or former cigarette smoking or vaping. Cannabis-smoking groups reported worse respiratory symptoms than never-smokers. High joint-year cannabis-smoking participants showed lower pre-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio, lower forced expiratory flow at 25-75% of the forced vital capacity, more radiographic emphysema and more ventilation abnormalities than never-smokers. Airway epithelial brushings from cannabis-smoking participants demonstrated an increased type 2 immune response, decreased type 17 immune response and higher MUC5AC gene expression than non-cannabis-smoking participants. Epithelial MUC5AC protein expression in cell cultures correlated with worse clinical outcomes and imaging abnormalities. CONCLUSIONS:Cannabis smoking, particularly at high exposures, is associated with worse respiratory symptoms, lower lung function, functional imaging abnormalities and dysregulated immune responses in the airway epithelium. These observations suggest respiratory harm associated with cannabis smoking and underscore the concerns for future respiratory morbidities related to persistent cannabis use.

Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (CT-FFR) has emerged as a critical tool for assessing functional ischemia in coronary artery disease (CAD). This expert consensus, developed by an international working group, provides a comprehensive overview of the clinical applications, diagnostic performance, and future perspectives of CT-FFR. The consensus highlights the use of CT-FFR as an indicator for abnormal coronary physiology, demonstrating superior diagnostic performance over anatomical CCTA alone, with pooled accuracy of 71

Background:Transcatheter heart valve (THV) underexpansion following transcatheter aortic valve implantation (TAVI) is associated with elevated gradients, paravalvular leak, and/or risk of hypoattenuating leaflet thickening. We aimed to simulate TAVI using pre-TAVI computed tomography (CT) images to predict the extent of THV underexpansion and the effect of staged balloon postdilatation on THV expansion. Methods:Patients who underwent balloon postdilatation as a staged procedure for symptomatic THV dysfunction following native or valve-in-valve TAVI with available pre-TAVI, post-TAVI, and post-balloon aortic valvuloplasty CT between 2016 and 2023 were analyzed. TAVI and postdilatation were simulated computationally in patient-specific models using finite element analysis. Simulations were performed in blinded fashion without information of index procedure. THV expansion was defined as the percentage of THV area achieved by THV in CT or modeling when compared to nominal area defined by THV manufacturer. Results:Among patients with balloon-expandable THVs following TAVI, the differences in expansion between CT and simulation measurements were -0.88% ± 3.27% (p = 0.75), -3.11% ± 4.65% (p = 0.26), and -3.27% ± 4.67% (p = 0.03) at the inflow, mid, and outflow regions, respectively. Following postdilatation, the differences in expansion between CT and simulation measurements were -0.60% ± 4.7% (p = 0.71), -1.64% ± 6.0% (p = 0.99), and -1.13% ± 4.2% (p = 0.55), respectively. Among patients with self-expandable THVs following TAVI, the percentage difference between CT and simulation measurements were 6.2% ± 4.2% (p = 0.99) and 9.3% ± 2.7% (p = 0.99) at the inflow and mid regions, respectively. Following postdilatation, the differences in expansion between CT and simulation measurements were 9.0% ± 3.2% and 8.9% ± 3.4%, respectively. Conclusions:Patient-specific computational modeling can predict THV underexpansion during the index procedure and the effect of postdilatation on THV expansion.

BACKGROUND Transcatheter heart valve (THV) underexpansion following transcatheter aortic valve implantation (TAVI) is associated with elevated gradients, paravalvular leak (PVL), and/or risk of hypoattenuating leaflet thickening. We aimed to simulate TAVI using pre-TAVI computed tomography (CT) images to predict the extent of THV underexpansion and the effect of staged balloon post-dilatation on THV expansion. METHODS Patients who underwent balloon post-dilatation as a staged procedure for symptomatic THV dysfunction following native or valve-in-valve (ViV) TAVI with available pre-TAVI, post-TAVI, and post–balloon aortic valvuloplasty (BAV) CT between 2016–2023 were analyzed. TAVI and post-dilatation were simulated computationally in patient-specific models using finite element analysis. All simulations were performed in blinded fashion without information of index procedure. THV expansion was defined as the percentage of THV area achieved by the THV in CT or modeling when compared to nominal area defined by THV manufacturer. RESULTS Among patients with balloon-expandable THVs following TAVI, the differences in expansion between CT and simulation measurements were −0.88% ± 3.27% (p = 0.75), −3.11% ± 4.65% (p = 0.26), and −3.27% ± 4.67% (p = 0.03) at the inflow, mid, and outflow regions, respectively. Following post-dilatation, the differences in expansion between CT and simulation measurements were −0.60% ± 4.7% (p = 0.71), −1.64% ± 6.0% (p = 0.99), and −1.13% ± 4.2% (p = 0.55), respectively. Among patients with self-expandable THVs following TAVI, the percentage difference between CT and simulation measurements were 6.2% ± 4.2% (p = 0.99) and 9.3% ± 2.7% (p = 0.99) at the inflow and mid regions, respectively. Following post-dilatation, the differences in expansion between CT and simulation measurements were 9.0% ± 3.2% and 8.9% ± 3.4%, respectively. CONCLUSIONS Patient-specific computational modeling can predict THV underexpansion during the index procedure and the effect of post-dilatation on THV expansion.

Left ventricular outflow tract (LVOT) obstruction is a possible complication following transcatheter mitral valve implantation (TMVI). Current geometric screening methods are limited because they do not account for dynamic fluid mechanics. While high-fidelity moving-wall computational models can predict these dynamics, they are too computationally intensive for routine clinical use. This study aims to develop a simplified computational fluid dynamics rigid model capable of accurately predicting post-TMVI LVOT gradient within minutes.Using a cohort of 16 mitral regurgitation patients, we developed moving-wall models as a baseline and compared them against rigid models with varying flow inlet heights. Equivalence tests were then carried out to assess the LVOT gradients obtained by clinical measurements, moving-wall and rigid models.The results demonstrated that a rigid model utilising a flow inlet at 60% LV height best approximated the LVOT gradients of complex moving-wall simulations. Specifically, this simplified model reduced simulation time from 12 hours to just 4 minutes. Equivalence testing showed that the rigid model predicted LVOT gradients with 90% confidence intervals within ±1 mmHg bounds of moving-wall results and ±3 mmHg bounds of clinical echocardiographic measurements.In conclusion, the developed rigid model (60% LV height from apex as flow inlet) reproduced the LVOT gradients using simplified boundary condition without complex wall-motion tracking. This approach goes beyond previous efforts by providing a robust and efficient tool that facilitates real-time clinical integration and large-scale research, ultimately improving patient safety and procedural planning for TMVI.

RATIONALE:Chronic obstructive pulmonary disease (COPD) is characterized by global immune dysregulation. The most abundant immune cells in the distal airways and alveolar compartments are macrophages and lymphocytes. These cells have been poorly characterized in human airways due to their plasticity and numerous subtypes. There is a marked scarcity of information in the COPD airway, limiting our understanding of the inflammatory process that drives COPD progression. OBJECTIVES:The primary aim of this study was to characterize the differences in composition of the immune cells in the alveolar space of patients with COPD versus healthy controls and the relation with severity of airflow limitation at a single-cell resolution. METHODS:Individuals with and without COPD were recruited. All participants underwent bronchoscopy, where a single-cell suspension was created from the retrieved bronchoalveolar lavage and then sequenced using single-cell RNA sequencing technology. Full pulmonary function tests, thoracic computed tomography (CT), and xenon-129 hyperpolarized gas magnetic resonance imaging (MRI) were performed on participants for phenotyping. MEASUREMENTS AND MAIN RESULTS:From 17 participants, a total of 97 254 cells were recovered, with 52 840 cells belonging to the COPD group (N = 10). The COPD immune landscape was perturbed and characterized by an expansion of non-typable macrophages, increased neutrophils and classical monocytes, and significant changes in regulatory and double-negative T lymphocytes compared to controls (FDR < 0.05). The percentage of these cells was further altered with increasing GOLD (Global Initiative for Chronic Obstructive Lung Disease) severity stages. The percentage of double-negative T cells in BAL was significantly related to airway luminal area on CT, whereas that of regulatory T cells was inversely related to MRI gas transfer and DLCO of COPD patients. CONCLUSIONS:The immune cell transcriptomic profile of COPD BAL reveals global immune dysregulation, with increased abundance of proinflammatory and profibrotic macrophages, monocytes, and neutrophils, potentially driving airway remodeling. Regulatory T cells may play a significant role in gas exchange perturbations of COPD.

BACKGROUND:Diabetes mellitus, smoking, hypertension, and hyperlipidemia are well-studied cardiovascular risk factors (CVRF) for coronary artery disease (CAD). However, their combined and individual influence on atherosclerotic total plaque volume (TPV) and plaque subtypes as assessed by coronary computed tomographic angiography (CCTA) has not been well evaluated. PURPOSE:To evaluate the association between CVRF on TPV and plaque subtypes and to develop quantitative plaque nomograms stratified by sex, age, and CVRF using CCTA findings. METHODS:This analysis included participants from the ADVANCE (Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care) registry. Quantitative assessment of TPV and plaque subtypes was performed using an Artificial Intelligence-Enabled Quantitative Coronary Plaque Analysis tool. RESULTS:A total of 4430 patients were included in the analysis, with a median age of 67.0 [59.0-73.0] years, and 1512 (34.1 %) were women. The median TPV was 390 mm3 (IQR: 163-760 mm3) and it was significantly higher in male participants (460 mm3; IQR 197-855 mm3) compared to female participants (280.5 mm3; IQR: 118-583 mm3) (P < 0.0001). Independent of sex, participants with CVRF had higher median TPVs (404.5 mm3; IQR: 175-788.5 mm3) than those without CVRF (187 mm3; IQR: 74-431 mm3) (P < 0.0001). On ROC analysis, age emerged as the strongest predictor of TPV >250 mm3 (AUC 0.62; CI: 0.60-0.64), with only modest improvements in the model after adding male sex (0.67; CI: 0.65-0.69) and CVRF (0.69; CI: 0.68-0.71). CONCLUSIONS:Our data indicate that TPV is significantly higher in participants with CVRF compared to those without. Age demonstrated the strongest association with plaque volume, while the addition of CVRF only modestly increased the AUC. Altogether, age and CVRF were only modestly associated with plaque volume, highlighting the need for further research to fully understand the potential and limitations of plaque imaging assessing the extent and severity of CAD, in patients with and without CVRF.

BACKGROUND:Statins are a cornerstone medication for coronary atherosclerosis. This study assessed whether radiomic analysis of coronary computed tomography angiography (CCTA) could predict patient response to statin therapy. METHODS:Patients from a multinational registry with serial CCTA (≥2-year intervals) on statin therapy were analyzed. Radiomic scores were calculated, categorizing patients as statin responders or non-responders (≥1.0% increase in percent atheroma volume (PAV) per year indicated non-response). Data were split into training (79%) and test (21%) sets based on sites. Four predictive models were developed: Model 1 used clinical risk factors (CRF), Model 2 included CRF, calcified and non-calcified PAV, and number of high-risk plaques. Model 3 used only the radiomic score, and Model 4 combined Models 2 and 3. RESULTS:A total of 386 statin responders (mean age 61.2 ​± ​8.4 years, 60.1% male) and 177 statin non-responders (mean age 63.2 ​± ​9.0 years, 44.1% male) were analyzed. Model 3, based solely on the radiomic score, demonstrated superior predictive power compared to Model 1 (area under the receiver operating characteristic curve [AUC] [95% confidence interval (CI)]: 0.75 [0.67-0.83] vs 0.54 [0.45-0.63], p ​< ​0.05) and was comparable to Model 2 (AUC [95% CI]: 0.82 [0.74-0.88], p ​> ​0.05) in the test set. Model 4 exhibited the highest power (AUC [95% CI]: 0.84 [0.77-0.90], all p ​< ​0.05 compared to Model 2 and Model 3). CONCLUSION:CCTA radiomic features show proof-of-concept for predicting statin response, warranting further validation. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov NCT0280341.

Rapid progression of coronary atherosclerosis is associated with an increased risk of future adverse cardiovascular events. However, evidence regarding the association between glycemic status and rapid plaque progression (RPP) in the major epicardial coronary arteries remains limited. A total of 1296 subjects (mean age, 61 ± 9 years; 56.9

Hyperpolarized xenon 129 (129Xe) MRI uses inhaled 129Xe gas to visualize pulmonary function and microstructure. This review aims to summarize established and emerging quantitative measurements derived from 129Xe MRI and MR spectroscopy (MRS) and illustrate their clinical applications in the characterization and management of cardiopulmonary diseases. They are well tolerated by adults and children with pulmonary disease, employ no ionizing radiation, and their measurements have been validated by correlation with pulmonary function tests in various cardiopulmonary diseases. 129Xe fills unobstructed airspaces, producing three-dimensional maps of ventilation and enabling quantification of ventilation defects, dynamics, and heterogeneity. Leveraging 129Xe's biologic solubility, gas exchange imaging and spectroscopy allow for quantification of gas transfer between airspaces, alveolar membrane, and red blood cells and are sensitive to blood oxygenation and vascular remodeling. Diffusion-weighted imaging quantifies airspace enlargement, providing models of alveolar microstructure. 129Xe MRI can help detect early-stage disease, adding value where reference-standard tools, such as pulmonary function tests, lack sensitivity. The ability of 129Xe MRI to assess function regionally creates opportunities for the detection of localized functional deficits and the improvement of image-guided interventions. Applications of 129Xe MRI and MRS include planning treatment, monitoring disease progression and treatment response, and developing surrogate endpoints for clinical and therapeutic studies. Keywords: MR Imaging, MR Spectroscopy, Thorax, Lung, Hyperpolarized 129Xe, MRI, MRS, Lung Function, Ventilation, Gas Exchange, Alveolar Microstructure © RSNA, 2025.

Background The impact of sex‐related differences in coronary atheroma and flow impairment severity on clinical events and costs remains unclear. Methods and Results This is a secondary analysis of patients with stable coronary artery disease who underwent both coronary computed tomography angiography and fractional flow reserve derived from computed tomography as part of the FORECAST (Fractional Flow Reserve Derived From Computed Tomography Coronary Angiography in the Assessment and Management of Stable Chest Pain) trial, investigating (1) the relationship between coronary stenosis severity on coronary computed tomography angiography and fractional flow reserve derived from computed tomography FFRCT by sex and (2) the association with revascularization, resource usage, and adverse clinical events. A total of 212 patients (64 female participants [32.1%]) and 1245 vessels were included. There was no significant sex difference in the frequencies of significant coronary artery disease (38.2% of women versus 51.3% of men; P=0.073), but female participants had significantly less coronary flow impairment, according to the presence of at least 1 fractional flow reserve derived from computed tomography≤0.8 (47.0% versus 71.5%; P=0.008). Female subjects underwent fewer revascularization procedures (23.5% versus 42.3%; P=0.014), less coronary artery bypass graft surgery (2.9% versus 13.1%; P=0.025) and were less likely to be on statin treatment (72.0% versus 84.7%; P=0.022) by 9‐month follow‐up. This resulted in lower overall health care costs for female participants compared with male counterparts (median total cost, £1276 versus £2051; P=0.014). In multivariable Cox analysis the presence of significant coronary artery disease (hazard ratio [HR], 2.91; 95% CI, 1.30–6.51) and having a positive fractional flow reserve derived from computed tomography (HR, 4.11; 95% CI, 1.15–14.69) were independent predictors of major adverse cardiovascular events at 9 months, whereas sex was not statistically significant (p=0.13). Conclusions There are significant sex differences in the anatomico‐functional assessment of coronary artery disease leading to differences in clinical management, costs, and adverse events.