Impact of immune checkpoint inhibitors on atherosclerosis progression in patients with lung cancer.

BACKGROUND: Patients with lung cancer face a heightened risk of atherosclerosis-related cardiovascular events. Despite the strong scientific rationale, there is currently a lack of clinical evidence examining the impact of immune checkpoint inhibitors (ICIs) on the advancement of atherosclerosis in patients with lung cancer. The objective of our study was to investigate whether there is a correlation between ICIs and the accelerated progression of atherosclerosis among individuals with lung cancer. METHODS: In this case-control (2:1 matched by age and gender) study, total, non-calcified, and calcified plaque volumes were measured in the thoracic aorta using sequential contrast-enhanced chest CT scans. Univariate and multivariate rank-based estimation regression models were developed to estimate the effect of ICI therapy on plaque progression in 40 cases (ICI) and 20 controls (non-ICI). RESULTS: The patients had a median age of 66 years (IQR: 58-69), with 50% of them being women. At baseline, there were no significant differences in plaque volumes between the groups, and their cardiovascular risk profiles were similar. However, the annual progression rate for non-calcified plaque volume was 7 times higher in the ICI group compared with the controls (11.2% vs 1.6% per year, p=0.001). Conversely, the controls showed a greater progression in calcified plaque volume compared with the ICI group (25% vs 2% per year, p=0.017). In a multivariate model that considered cardiovascular risk factors, the use of an ICI was associated with a more substantial progression of non-calcified plaque volume. Additionally, individuals treated with combination ICI therapy exhibited greater plaque progression. CONCLUSIONS: ICI therapy was associated with more non-calcified plaque progression. These findings underscore the importance of conducting studies aimed at identifying the underlying mechanisms responsible for plaque advancement in patients undergoing ICI treatment. TRIAL REGISTRATION NUMBER: NCT04430712.

Pericardial disease in patients treated with immune checkpoint inhibitors.

BACKGROUND: There are limited data on the occurrence, associations and outcomes of pericardial effusions and pericarditis on or after treatment with immune checkpoint inhibitors (ICIs). METHODS: This was a retrospective study at a single academic center that compared 2842 consecutive patients who received ICIs with 2699 age- and cancer-type matched patients with metastatic disease who did not receive ICI. A pericardial event was defined as a composite outcome of pericarditis and new or worsening moderate or large pericardial effusion. The endpoints were obtained through chart review and were blindly adjudicated. To identify risk factors associated with a pericardial event, we compared patients who developed an event on an ICI with patients treated with an ICI who did not develop a pericardial event. Cox proportional-hazard model and logistical regression analysis were performed to study the association between ICI use and pericardial disease as well as pericardial disease and mortality. An additional 6-week landmark analysis was performed to account for lead-time bias. RESULTS: There were 42 pericardial events in the patients treated with ICI (n=2842) over 193 days (IQR: 64-411), yielding an incidence rate of 1.57 events per 100 person-years. There was a more than fourfold increase in risk of pericarditis or a pericardial effusion among patients on an ICI compared with controls not treated with ICI after adjusting for potential confounders (HR 4.37, 95% CI 2.09 to 9.14, p<0.001). Patients who developed pericardial disease while on an ICI had a trend for increased all-cause mortality compared with patients who did not develop a pericardial event (HR 1.53, 95% CI 0.99 to 2.36, p=0.05). When comparing those who developed pericardial disease after ICI treatment with those who did not, a higher dose of corticosteroid pre-ICI (>0.7 mg/kg prednisone) was associated with increased risk of pericardial disease (HR 2.56, 95% CI 1.00 to 6.57, p=0.049). CONCLUSIONS: ICI use was associated with an increased risk of development of pericardial disease among patients with cancer and a pericardial event on an ICI was associated with a trend towards increase in mortality.

Calcium scoring: a personalized probability assessment predicts the need for additional or alternative testing to coronary CT angiography.

OBJECTIVE: To assess whether anthropometrics, clinical risk factors, and coronary artery calcium score (CACS) can predict the need of further testing after coronary CT angiography (CTA) due to non-diagnostic image quality and/or the presence of significant stenosis. METHODS: Consecutive patients who underwent coronary CTA due to suspected coronary artery disease (CAD) were included in our retrospective analysis. We used multivariate logistic regression and receiver operating characteristics analysis containing anthropometric factors: body mass index, heart rate, and rhythm irregularity (model 1); and parameters used for pre-test likelihood estimation: age, sex, and type of angina (model 2); and also added total calcium score (model 3) to predict downstream testing. RESULTS: We analyzed 4120 (45.7% female, 57.9 ± 12.1 years) patients. Model 3 significantly outperformed models 1 and 2 (area under the curve, 0.84 [95% CI 0.83-0.86] vs. 0.56 [95% CI 0.54-0.58] and 0.72 [95% CI 0.70-0.74], p < 0.001). For patients with sinus rhythm of 50 bpm, in case of non-specific angina, CACS above 435, 756, and 944; in atypical angina CACS above 381, 702, and 890; and in typical angina CACS above 316, 636, and 824 correspond to 50%, 80%, and 90% probability of further testing, respectively. However, higher heart rates and arrhythmias significantly decrease these cutoffs (p < 0.001). CONCLUSION: CACS significantly increases the ability to identify patients in whom deferral from coronary CTA may be advised as CTA does not lead to a final decision regarding CAD management. Our results provide individualized cutoff values for given probabilities of the need of additional testing, which may facilitate personalized decision-making to perform or defer coronary CTA. KEY POINTS: • Anthropometric parameters on their own are insufficient predictors of downstream testing. Adding parameters of the Diamond and Forrester pre-test likelihood test significantly increases the power of prediction. • Total CACS is the most important independent predictor to identify patients in whom coronary CTA may not be recommended as CTA does not lead to a final decision regarding CAD management. • We determined specific CACS cutoff values based on the probability of downstream testing by angina-, arrhythmia-, and heart rate-based groups of patients to help individualize patient management.

Computed Tomographic Angiography for Risk Stratification in Patients with Acute Chest Pain - The Triple Rule-out Concept in the Emergency Department.

BACKGROUND: Acute chest pain is one of the most common reasons for Emergency Department (ED) visits and hospital admissions. As this could represent the first symptom of a lifethreatening condition, urgent identification of the etiology of chest pain is of utmost importance in emergency settings. Such high-risk conditions that can present with acute chest pain in the ED include Acute Coronary Syndromes (ACS), Pulmonary Embolisms (PE) and Acute Aortic Syndromes (AAS). DISCUSSION: The concept of Triple Rule-out Computed Tomographic Angiography (TRO-CTA) for patients presenting with acute chest pain in the ED is based on the use of coronary computed tomographic angiography as a single imaging technique, able to diagnose or exclude three lifethreatening conditions in one single step: ACS, AAS and PE. TRO-CTA protocols have been proved to be efficient in the ED for diagnosis or exclusion of life-threatening conditions and for differentiation between various etiologies of chest pain, and application of the TRO-CTA protocol in the ED for acute chest pain of uncertain etiology has been shown to improve the further clinical evaluation and outcomes of these patients. CONCLUSION: This review aims to summarize the main indications and techniques used in TRO protocols in EDs, and the role of TRO-CTA protocols in risk stratification of patients with acute chest pain.

Effect of image reconstruction algorithms on volumetric and radiomic parameters of coronary plaques.

BACKGROUND: Volumetric and radiomic analysis of atherosclerotic plaques on coronary CT angiography have been shown to predict high-risk plaque morphology and to predict patient outcomes. However, there is limited information whether image reconstruction algorithms and preprocessing steps (type of binning, number of bins used for discretization) may influence parameter values. METHODS: We retrospectively identified 60 coronary lesions on coronary CT angiography (CTA). All images were reconstructed using filtered back projection (FBP), hybrid (HIR) and model-based (MIR) iterative reconstruction. Plaques were segmented manually on HIR images and copied to FBP and MIR images to ensure identical voxels were analyzed. Overall, 4 volumetric and 169 radiomic parameters were calculated. Intra-class correlation coefficient (ICC) was used to assess reproducibility between image reconstructions, while linear regression analysis was used to assess the effect of preprocessing steps done before calculating radiomic metrics. RESULTS: All volumetric and radiomic metrics had ICC>0.90 except for first-order statistics: mode, harmonic mean, minimum (0.45, 0.76, 0.84; respectively) and gray level co-occurrence (GLCM) parameters: inverse difference sum and sum variance (0.01, 0.04; respectively). Among GLCM parameters 90% were significantly affected by the type of binning and 100% by the number of bins. In case of gray level run length matrix parameters 100% of metrics were affected by both preprocessing steps. CONCLUSIONS: Volumetric and radiomic statistics are robust to image reconstruction algorithms. However, all radiomic variables were affected by preprocessing steps therefore, showing the need for standardization before being implemented into everyday clinical practice.