Ultra-high-resolution photon-counting detector CT in evaluating coronary stent patency: a comparison to invasive coronary angiography.

OBJECTIVES: To determine the diagnostic accuracy of ultra-high-resolution photon-counting detector CT angiography (UHR PCD-CTA) for evaluating coronary stent patency compared to invasive coronary angiography (ICA). METHODS: Consecutive, clinically referred patients with prior coronary stent implantation were prospectively enrolled between August 2022 and March 2023 and underwent UHR PCD-CTA (collimation, 120 × 0.2 mm). Two radiologists independently analyzed image quality of the in-stent lumen using a 5-point Likert scale, ranging from 1 ("excellent") to 5 ("non-diagnostic"), and assessed all coronary stents for the presence of in-stent stenosis (≥ 50% lumen narrowing). The diagnostic accuracy of UHR PCD-CTA was determined, with ICA serving as the standard of reference. RESULTS: A total of 44 coronary stents in 18 participants (mean age, 83 years ± 6 [standard deviation]; 12 women) were included in the analysis. In 3/44 stents, both readers described image quality as non-diagnostic, whereas reader 2 noted a fourth stent to have non-diagnostic image quality. In comparison to ICA, UHR PCD-CTA demonstrated a sensitivity, specificity, and accuracy of 100% (95% CI [confidence interval] 47.8, 100), 92.3% (95% CI 79.1, 98.4), and 93.2% (95% CI 81.3, 98.6) for reader 1 and 100% (95% CI 47.8, 100), 87.2% (95% CI 72.6, 95.7), and 88.6% (95% CI 75.4, 96.2) for reader 2, respectively. Both readers observed a 100% negative predictive value (36/36 stents and 34/34 stents). Stent patency inter-reader agreement was 90.1%, corresponding to a substantial Cohen's kappa value of 0.72. CONCLUSIONS: UHR PCD-CTA enables non-invasive assessment of coronary stent patency with high image quality and diagnostic accuracy. CLINICAL RELEVANCE STATEMENT: Ultra-high-resolution photon-counting detector CT angiography represents a reliable and non-invasive method for assessing coronary stent patency. Its high negative predictive value makes it a promising alternative over invasive coronary angiography for the rule-out of in-stent stenosis. KEY POINTS: • CT-based evaluation of coronary stent patency is limited by stent-induced artifacts and spatial resolution. • Ultra-high-resolution photon-counting detector CT accurately evaluates coronary stent patency compared to invasive coronary angiography. • Photon-counting detector CT represents a promising method for the non-invasive rule-out of in-stent stenosis.

Nonpreferential but Detrimental Accumulation of Macrophages With Clonal Hematopoiesis-Driver Mutations in Cardiovascular Tissues-Brief Report.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is an acquired genetic risk factor for both leukemia and cardiovascular disease. It results in proinflammatory myeloid cells in the bone marrow and blood; however, how these cells behave in the cardiovascular tissue remains unclear. Our study aimed at investigating whether CHIP-mutated macrophages accumulate preferentially in cardiovascular tissues and examining the transcriptome of tissue macrophages from DNMT3A (DNA methyltransferase 3 alpha) or TET2 (Tet methylcytosine dioxygenase 2) mutation carriers. METHODS: We recruited patients undergoing carotid endarterectomy or heart surgeries to screen for CHIP mutation carriers using targeted genomic sequencing. Myeloid and lymphoid cells were isolated from blood and cardiovascular tissue collected during surgeries using flow cytometry. DNA and RNA extracted from these sorted cells were subjected to variant allele frequency measurement using droplet digital polymerase chain reaction and transcriptomic profiling using bulk RNA sequencing, respectively. RESULTS: Using droplet digital polymerase chain reaction, we detected similar variant allele frequency of CHIP in monocytes from blood and macrophages from atheromas and heart tissues, even among heart macrophages with and without CCR2 (C-C motif chemokine receptor 2) expression. Bulk RNA sequencing revealed a proinflammatory gene profile of myeloid cells from DNMT3A or TET2 mutation carriers compared with those from noncarriers. CONCLUSIONS: Quantitatively, CHIP-mutated myeloid cells did not preferentially accumulate in cardiovascular tissues, but qualitatively, they expressed a more disease-prone phenotype.

Photon-counting computed tomography - clinical application in oncological, cardiovascular, and pediatric radiology. / Photon-Counting Computertomographie ­ klinische Anwendungen in der onkologischen, kardiovaskulären und pädiatrischen Radiologie.

BACKGROUND: Photon-counting detector computed tomography (PCD-CT) is a promising new technology with the potential to fundamentally change workflows in the daily routine and provide new quantitative imaging information to improve clinical decision-making and patient management. METHOD: The contents of this review are based on an unrestricted literature search of PubMed and Google Scholar using the search terms "photon-counting CT", "photon-counting detector", "spectral CT", "computed tomography" as well as on the authors' own experience. RESULTS: The fundamental difference with respect to the currently established energy-integrating CT detectors is that PCD-CT allows for the counting of every single photon at the detector level. Based on the identified literature, PCD-CT phantom measurements and initial clinical studies have demonstrated that the new technology allows for improved spatial resolution, reduced image noise, and new possibilities for advanced quantitative image postprocessing. CONCLUSION: For clinical practice, the potential benefits include fewer beam hardening artifacts, a radiation dose reduction, and the use of new or combinations of contrast agents. In particular, critical patient groups such as oncological, cardiovascular, lung, and head & neck as well as pediatric patient collectives benefit from the clinical advantages. KEY POINTS: · Photon-counting computed tomography (PCD-CT) is being used for the first time in routine clinical practice, enabling a significant dose reduction in critical patient populations such as oncology, cardiology, and pediatrics.. · Compared to conventional CT, PCD-CT enables a reduction in electronic image noise.. · Due to the spectral data sets, PCD-CT enables fully comprehensive post-processing applications.. CITATION FORMAT: · Hagen F, Soschynski M, Weis M et al. Photon-counting computed tomography - clinical application in oncological, cardiovascular, and pediatric radiology. Fortschr Röntgenstr 2024; 196: 25 - 34.

Accuracy of Ultrahigh-Resolution Photon-counting CT for Detecting Coronary Artery Disease in a High-Risk Population.

Background Recently introduced photon-counting CT may improve noninvasive assessment of patients with high risk for coronary artery disease (CAD). Purpose To determine the diagnostic accuracy of ultrahigh-resolution (UHR) coronary CT angiography (CCTA) in the detection of CAD compared with the reference standard of invasive coronary angiography (ICA). Materials and Methods In this prospective study, participants with severe aortic valve stenosis and clinically indicated CT for transcatheter aortic valve replacement planning were consecutively enrolled from August 2022 to February 2023. All participants were examined with a dual-source photon-counting CT scanner using a retrospective electrocardiography-gated contrast-enhanced UHR scanning protocol (tube voltage, 120 or 140 kV; collimation, 120 × 0.2 mm; 100 mL of iopromid; no spectral information). Subjects underwent ICA as part of their clinical routine. A consensus assessment of image quality (five-point Likert scale: 1 = excellent [absence of artifacts], 5 = nondiagnostic [severe artifacts]) and a blinded independent reading for the presence of CAD (stenosis ≥50%) were performed. UHR CCTA was compared with ICA using area under the receiver operating characteristic curve (AUC). Results Among 68 participants (mean age, 81 years ± 7 [SD]; 32 male, 36 female), the prevalence of CAD and prior stent placement was 35% and 22%, respectively. The overall image quality was excellent (median score, 1.5 [IQR, 1.3-2.0]). The AUC of UHR CCTA in the detection of CAD was 0.93 per participant (95% CI: 0.86, 0.99), 0.94 per vessel (95% CI: 0.91, 0.98), and 0.92 per segment (95% CI: 0.87, 0.97). Sensitivity, specificity, and accuracy, respectively, were 96%, 84%, and 88% per participant (n = 68); 89%, 91%, and 91% per vessel (n = 204); and 77%, 95%, and 95% per segment (n = 965). Conclusion UHR photon-counting CCTA provided high diagnostic accuracy in the detection of CAD in a high-risk population, including subjects with severe coronary calcification or prior stent placement. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Williams and Newby in this issue.

Elevated platelet-leukocyte complexes are associated with, but dispensable for myocardial ischemia-reperfusion injury.

AIMS: P-selectin is an activatable adhesion molecule on platelets promoting platelet aggregation, and platelet-leukocyte complex (PLC) formation. Increased numbers of PLC are circulating in the blood of patients shortly after acute myocardial infarction and predict adverse outcomes. These correlations led to speculations about whether PLC may represent novel therapeutic targets. We therefore set out to elucidate the pathomechanistic relevance of PLC in myocardial ischemia and reperfusion injury. METHODS AND RESULTS: By generating P-selectin deficient bone marrow chimeric mice, the post-myocardial infarction surge in PLC numbers in blood was prevented. Yet, intravital microscopy, flow cytometry and immunohistochemical staining, echocardiography, and gene expression profiling showed unequivocally that leukocyte adhesion to the vessel wall, leukocyte infiltration, and myocardial damage post-infarction were not altered in response to the lack in PLC. CONCLUSION: We conclude that myocardial infarction associated sterile inflammation triggers PLC formation, reminiscent of conserved immunothrombotic responses, but without PLC influencing myocardial ischemia and reperfusion injury in return. Our experimental data do not support a therapeutic concept of selectively targeting PLC formation in myocardial infarction.

Circulating Autoantibodies Recognizing Immunodominant Epitopes From Human Apolipoprotein B Associate With Cardiometabolic Risk Factors, but Not With Atherosclerotic Disease.

Rationale: Atherosclerosis is a chronic inflammatory disease of large arteries that involves an autoimmune response with autoreactive T cells and auto-antibodies recognizing Apolipoprotein B (ApoB), the core protein of low-density lipoprotein (LDL). Here, we aimed to establish a clinical association between circulating human ApoB auto-antibodies with atherosclerosis and its clinical risk factors using a novel assay to detect auto-antibodies against a pool of highly immunogenic ApoB-peptides. Methods and Results: To detect polyclonal IgM- and IgG-antibodies recognizing ApoB, we developed a chemiluminescent sandwich ELISA with 30 ApoB peptides selected by an in silico assay for a high binding affinity to MHC-II, which cover more than 80% of known MHC-II variants in a Caucasian population. This pre-selection of immunogenic self-peptides accounted for the high variability of human MHC-II, which is fundamental to allow T cell dependent generation of IgG antibodies. We quantified levels of ApoB-autoantibodies in a clinical cohort of 307 patients that underwent coronary angiography. Plasma anti-ApoB IgG and IgM concentrations showed no differences across healthy individuals (n = 67), patients with coronary artery disease (n = 179), and patients with an acute coronary syndrome (n = 61). However, plasma levels of anti-ApoB IgG, which are considered pro-inflammatory, were significantly increased in patients with obesity (p = 0.044) and arterial hypertension (p < 0.0001). In addition, patients diagnosed with the metabolic syndrome showed significantly elevated Anti-ApoB IgG (p = 0.002). Even when normalized for total plasma IgG, anti-ApoB IgG remained highly upregulated in hypertensive patients (p < 0.0001). We observed no association with triglycerides, total cholesterol, VLDL, or LDL plasma levels. However, total and normalized anti-ApoB IgG levels negatively correlated with HDL. In contrast, total and normalized anti-ApoB IgM, that have been suggested as anti-inflammatory, were significantly lower in diabetic patients (p = 0.012) and in patients with the metabolic syndrome (p = 0.005). Conclusion: Using a novel ELISA method to detect auto-antibodies against ApoB in humans, we show that anti-ApoB IgG associate with cardiovascular risk factors but not with the clinical appearance of atherosclerosis, suggesting that humoral immune responses against ApoB are shaped by cardiovascular risk factors but not disease status itself. This novel tool will be helpful to develop immune-based risk stratification for clinical atherosclerosis in the future.

Myeloid cell-specific Irf5 deficiency stabilizes atherosclerotic plaques in Apoe-/- mice.

OBJECTIVE: Interferon regulatory factor (IRF) 5 is a transcription factor known for promoting M1 type macrophage polarization in vitro. Given the central role of inflammatory macrophages in promoting atherosclerotic plaque progression, we hypothesize that myeloid cell-specific deletion of IRF5 is protective against atherosclerosis. METHODS: Female Apoe-/-LysmCre/+Irf5fl/fl and Apoe-/-Irf5fl/fl mice were fed a high-cholesterol diet for three months. Atherosclerotic plaque size and compositions as well as inflammatory gene expression were analyzed. Mechanistically, IRF5-dependent bone marrow-derived macrophage cytokine profiles were tested under M1 and M2 polarizing conditions. Mixed bone marrow chimeras were generated to determine intrinsic IRF5-dependent effects on macrophage accumulation in atherosclerotic plaques. RESULTS: Myeloid cell-specific Irf5 deficiency blunted LPS/IFNγ-induced inflammatory gene expression in vitro and in the atherosclerotic aorta in vivo. While atherosclerotic lesion size was not reduced in myeloid cell-specific Irf5-deficient Apoe-/- mice, plaque composition was favorably altered, resembling a stable plaque phenotype with reduced macrophage and lipid contents, reduced inflammatory gene expression and increased collagen deposition alongside elevated Mertk and Tgfß expression. Irf5-deficient macrophages, when directly competing with wild type macrophages in the same mouse, were less prone to accumulate in atherosclerotic lesion, independent of monocyte recruitment. Irf5-deficient monocytes, when exposed to oxidized low density lipoprotein, were less likely to differentiate into macrophage foam cells, and Irf5-deficient macrophages proliferated less in the plaque. CONCLUSION: Our study provides genetic evidence that selectively altering macrophage polarization induces a stable plaque phenotype in mice.

Outcome Prediction in Patients with Severe COVID-19 Requiring Extracorporeal Membrane Oxygenation-A Retrospective International Multicenter Study.

The role of veno-venous extracorporeal membrane oxygenation therapy (V-V ECMO) in severe COVID-19 acute respiratory distress syndrome (ARDS) is still under debate and conclusive data from large cohorts are scarce. Furthermore, criteria for the selection of patients that benefit most from this highly invasive and resource-demanding therapy are yet to be defined. In this study, we assess survival in an international multicenter cohort of COVID-19 patients treated with V-V ECMO and evaluate the performance of several clinical scores to predict 30-day survival. METHODS: This is an investigator-initiated retrospective non-interventional international multicenter registry study (NCT04405973, first registered 28 May 2020). In 127 patients treated with V-V ECMO at 15 centers in Germany, Switzerland, Italy, Belgium, and the United States, we calculated the Sequential Organ Failure Assessment (SOFA) Score, Simplified Acute Physiology Score II (SAPS II), Acute Physiology And Chronic Health Evaluation II (APACHE II) Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score, Predicting Death for Severe ARDS on V­V ECMO (PRESERVE) Score, and 30-day survival. RESULTS: In our study cohort which enrolled 127 patients, overall 30-day survival was 54%. Median SOFA, SAPS II, APACHE II, RESP, and PRESERVE were 9, 36, 17, 1, and 4, respectively. The prognostic accuracy for all these scores (area under the receiver operating characteristic-AUROC) ranged between 0.548 and 0.605. CONCLUSIONS: The use of scores for the prediction of mortality cannot be recommended for treatment decisions in severe COVID-19 ARDS undergoing V-V ECMO; nevertheless, scoring results below or above a specific cut-off value may be considered as an additional tool in the evaluation of prognosis. Survival rates in this cohort of COVID-19 patients treated with V­V ECMO were slightly lower than those reported in non-COVID-19 ARDS patients treated with V-V ECMO.

Cardiogenic shock: incidence, survival and mechanical circulatory support usage 2007-2017-insights from a national registry.

BACKGROUND: A central element in the management of cardiogenic shock (CS) comprises mechanical circulatory support (MCS) systems to maintain cardiac output (CO). This study aims to quantify incidence, outcome and influence of MCS in CS over the last decade. METHODS: All patients hospitalized with CS in a tertiary university hospital in Germany between 2007 and 2017 were identified utilizing the international coding system ICD-10 with code R57.0. Application of MCS was identified via German procedure classification codes (OPS). RESULTS: 383,983 cases of cardiogenic shock were reported from 2007 to 2017. Patients had a mean age of 71 years and 38.5% were female. The incidence of CS rose by 65.6% from 26,828 cases in 2007 (33.1 per 100,000 person-years, hospital survival 39.2%) to 44,425 cases in 2017 (53.7 per 100,000 person-years, survival 41.2%). In 2007, 16.0% of patients with CS received MCS (4.6 per 100,000 person-years, survival 46.6%), dropping to 13.9% in 2017 (6.6 per 100,000 person-years, survival 38.6%). Type of MCS changed over the years, with decreasing use of the intra-aortic balloon pump (IABP), an increase in extracorporeal membrane oxygenation (VA-ECMO) and percutaneous ventricular assist device (pVAD) usage. Significant differences regarding in-hospital survival were observed between the devices (survival: overall: 40.2%; medical treatment = 39.5%; IABP = 49.5%; pVAD = 36.2%; VA-ECMO = 30.5%; p < 0.001). CONCLUSIONS: The incidence of CS is increasing, but hospital survival remains low. MCS was used in a minority of patients, and the percentage of MCS usage in CS has decreased. The use rates of the competing devices change over time.

Predictors of survival in patients with acute coronary syndrome undergoing percutaneous coronary intervention of unprotected left main coronary artery stenosis.

OBJECTIVE: Aim of this study was to investigate predictors of survival in unstable patients with high SYNTAX-1-score. BACKGROUND: In significant unprotected left main coronary artery (ULMCA) stenosis, treatment options include percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). While CABG is recommended for stable patients with ULMCA stenosis and a SYNTAX-1-score > 32, PCI may be preferable in unstable or high operative risk patients. METHODS: Retrospective single-center all-comers registry study. RESULTS: A total of 142 patients underwent ULMCA-PCI (~72.9 years, 23.2% females, 54.2% survival in 2-year follow-up), 84 of whom had a SYNTAX-1 > 32 (37.4 ± 12.8). Patients in the high-SYNTAX-1-group (score > 32) were more often in an acute condition compared to low-SYNTAX-2-group (score ≤ 32) including acute myocardial infarction (76.2% vs. 57.4%, p = .024), cardiogenic shock (48.2% vs. 14.8%, p = .001), or need for mechanical support (36.1% vs. 11.1%, p = .001). Survival was predicted by the acute condition including cardiogenic shock (OR 0.06 and 0.05) and myocardial infarction (OR 0.03 and 0.34) in both groups. Performance of the SYNTAX-1-score was limited in our patient collective in both groups (c-index 0.65 vs. 0.63) while SYNTAX-2-PCI-score performed better (c-index 0.67 vs. 0.67). EuroScore II had the best discriminative ability (c-index 0.87 vs. 0.78). CONCLUSIONS: The majority of patients undergoing ULMCA-PCI presented in acute conditions with high SYNTAX-1-score, and is therefore underrepresented in clinical trials. Prognosis was best predicted by the acute condition and the EuroScore II. These data suggest that therapy in unstable patients should be guided by clinical condition over the anatomical SYNTAX-1-score.

Imaging assessment of bioresorbable vascular scaffolds.

Vascular reparative therapy has become a reality with bioresorbable scaffolds (BRSs). To assess acute and long-term performance of the device, multimodality imaging would be essential. Radiopacity of metal hinders the imaging assessment, whereas radiolucent polymeric scaffolds allow for a precise imaging assessment with either invasive or non-invasive modality at baseline and at follow-up, which is one of the advantages of polymeric BRSs. Recent large trials evaluating clinical results of the first-generation BRS technology raised concerns about the safety and efficacy of these devices, namely, scaffold thrombosis. Intensive research with multimodality imaging in the field is being conducted to have in-depth understanding of the issues, which will facilitate the improvement of implantation techniques and the development of the next-generation BRSs. The current review focuses on the clinical application of the imaging modalities to assess the short- and long-term performance of the Absorb BVS.