Coronary heart disease is a common cause of death despite being preventable. To treat the underlying plaque deposits in the arterial walls, intravascular optical coherence tomography can be used by ...experts to detect and characterize the lesions. In clinical routine, hundreds of images are acquired for each patient, which require automatic plaque detection for fast and accurate decision support. So far, automatic approaches rely on classic machine learning methods and deep learning solutions have rarely been studied. Given the success of deep learning methods with other imaging modalities, a thorough understanding of deep learning-based plaque detection for future clinical decision support systems is required. We address this issue with a new data set consisting of in vivo patient images labeled by three trained experts. Using this data set, we employ the state-of-the-art deep learning models that directly learn plaque classification from the images. For improved performance, we study different transfer learning approaches. Furthermore, we investigate the use of Cartesian and polar image representations and employ data augmentation techniques tailored to each representation. We fuse both representations in a multi-path architecture for more effective feature exploitation. Last, we address the challenge of plaque differentiation in addition to detection. Overall, we find that our combined model performs best with an accuracy of 91.7%, a sensitivity of 90.9%, and a specificity of 92.4%. Our results indicate that building a deep learning-based clinical decision support system for plaque detection is feasible.
Background:The association between cardiovascular risk factors (CVRF) and the risk of coronary events is widely acknowledged. Whether individual risk factors may be associated with distinct plaque ...characteristics is currently unclear. We investigated the relationship between CVRF and coronary plaque burden and phenotype.Methods and Results:We assessed coronary atherosclerotic plaque characteristics by optical coherence tomography in 67 patients with stable coronary artery disease undergoing coronary angiography. The plaque burden and the distinct plaque phenotypes were compared with regard to different CVRF. Overall plaque burden was significantly greater in patients with diabetes mellitus (P=0.010), prediabetes (P=0.035) and obesity (P=0.024), and correlated with the number of CVRF (R=0.358, P=0.003). Patients with diabetes had a greater extent of fibroatheroma (P=0.015), calcific fibroatheroma (P=0.031), thin-cap fibroatheroma (TCFA-P=0.011) and plaque erosion (P=0.002). Obese patients showed a greater extent of fibroatheroma (P=0.007), TCFA (P=0.015) and macrophage load (P=0.043). The number of CVRF correlated with fibroatheroma (R=0.425, P<0.001), calcific fibroatheroma (R=0.321, P=0.008), TCFA (R=0.347, P=0.004), macrophage load (R=0.314, P=0.010) and erosion (R=0.271, P=0.029). In the multivariate analysis, altered glycemic status and obesity were the only independent predictors of TCFA (P=0.026 and P=0.046, respectively), whereas altered glycemic status was the only independent predictor of plaque erosion (P=0.001).Conclusions:Patients with diabetes, prediabetes and obesity show more extensive coronary atherosclerosis and more vulnerable plaque phenotypes.
Circulating microRNAs (miRs) may reflect pathophysiologically relevant processes in the atherosclerotically diseased coronary arterial wall. Given the unmet medical need to identify patients with an ...unstable plaque phenotype, we determined the relation of circulating atherosclerosis-regulatory miRs with plaque phenotypes.
We assessed coronary atherosclerotic plaque burden and phenotype by optical coherence tomography in 52 patients and measured the levels of circulating miRs across the transcoronary gradient. The overall plaque load was significantly correlated with transcoronary concentration gradients of miR-126-3p (P = 0.04), miR-145-5p (P = 0.01), miR-155-5p (P < 0.01), and miR-29b-3p (P = 0.02), but not with other miRs such as miR-92a-3p. In patients with a high extent of vulnerable plaques as assessed by the presence of thin-cap fibroatheromas (TCFAs), significantly higher transcoronary gradients were observed, particularly for miR-126-3p, miR-126-5p, and miR-145-5p (all P < 0.02). Transcoronary gradients of miR-126-3p (P < 0.01), miR-126-5p (P < 0.01), miR-145-5p (P = 0.01), miR-29b-3p (P = 0.03), and miR-155-5p (P = 0.02) demonstrated a significant discriminatory power to predict the presence of TCFAs (AUC > 0.7 for all). Moreover, aortic and venous coronary sinus levels of miR-29b-3p were inversely correlated with plaque fibrosis, a finding that is consistent with the anti-fibrotic activity of miR-29b-3p.
The overall plaque burden and plaque phenotypes are associated with changes in the kinetics of miR-concentrations across the transcoronary passage. Transcoronary gradients of the anti-atherosclerotic miR-126-3p and miR-145-5p correlated with the extent of TCFAs, suggesting that instable plaques may affect the local uptake or degradation of these miRs.
Targeted quantitative mass spectrometry metabolite profiling is the workhorse of metabolomics research. Robust and reproducible data are essential for confidence in analytical results and are ...particularly important with large-scale studies. Commercial kits are now available which use carefully calibrated and validated internal and external standards to provide such reliability. However, they are still subject to processing and technical errors in their use and should be subject to a laboratory’s routine quality assurance and quality control measures to maintain confidence in the results. We discuss important systematic and random measurement errors when using these kits and suggest measures to detect and quantify them. We demonstrate how wider analysis of the entire data set alongside standard analyses of quality control samples can be used to identify outliers and quantify systematic trends to improve downstream analysis. Finally, we present the MeTaQuaC software which implements the above concepts and methods for Biocrates kits and other target data sets and creates a comprehensive quality control report containing rich visualization and informative scores and summary statistics. Preliminary unsupervised multivariate analysis methods are also included to provide rapid insight into study variables and groups. MeTaQuaC is provided as an open source R package under a permissive MIT license and includes detailed user documentation.
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IJS, KILJ, NUK, PNG, UL, UM
Abstract
Aims
Mosaic loss of Y chromosome (LOY) in blood cells is the most common acquired mutation, increases with age, and is related to cardiovascular disease. Loss of Y chromosome induces cardiac ...fibrosis in murine experiments mimicking the consequences of aortic valve stenosis, the prototypical age-related disease. Cardiac fibrosis is the major determinant of mortality even after transcatheter aortic valve replacement (TAVR). It was hypothesized that LOY affects long-term outcome in men undergoing TAVR.
Methods and results
Using digital PCR in DNA of peripheral blood cells, LOY (Y/X ratio) was assessed by targeting a 6 bp sequence difference between AMELX and AMELY genes using TaqMan. The genetic signature of monocytes lacking the Y chromosome was deciphered by scRNAseq. In 362 men with advanced aortic valve stenosis undergoing successful TAVR, LOY ranged from −4% to 83.4%, and was >10% in 48% of patients. Three-year mortality increased with LOY. Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off of LOY >17% to predict mortality. In multivariate analysis, LOY remained a significant (P < 0.001) independent predictor of death during follow-up. scRNAseq disclosed a pro-fibrotic gene signature with LOY monocytes displaying increased expression of transforming growth factor (TGF) β-associated signaling, while expression of TGFβ-inhibiting pathways was down-regulated.
Conclusion
This is the first study to demonstrate that LOY in blood cells is associated with profoundly impaired long-term survival even after successful TAVR. Mechanistically, the pro-fibrotic gene signature sensitizing the patient-derived circulating LOY monocytes for the TGFβ signaling pathways supports a prominent role of cardiac fibrosis in contributing to the effects of LOY observed in men undergoing TAVR.
Structured Graphical Abstract
Structured Graphical Abstract
Mosaic loss of Y chromosome and mortality post TAVR.
New ischaemic brain lesions on magnetic resonance imaging (MRI) are reported in up to 86% of patients after transcatheter edge-to-edge repair of the mitral valve (TEER-MV). Knowledge of the exact ...procedural step(s) that carry the highest risk for cerebral embolisation may help to further improve the procedure.
The aim of this study was to identify the procedural step(s) that are associated with an increased risk of cerebral embolisation during TEER-MV with the MitraClip system. Furthermore, the risk of overt stroke and silent brain ischaemia after TEER-MV was assessed.
In this prospective, pre-specified observational study, all patients underwent continuous transcranial Doppler examination during TEER-MV to detect microembolic signals (MES). MES were assigned to specific procedural steps: (1) transseptal puncture and placement of the guide, (2) advancing and adjustment of the clip in the left atrium, (3) device interaction with the MV, and (4) removal of the clip delivery system and the guide. Neurological examination using the National Institutes of Health Stroke Scale (NIHSS) and cerebral MRI were performed before and after TEER-MV.
Fifty-four patients were included. The number of MES differed significantly between the procedural steps with the highest numbers observed during device interaction with the MV. Mild neurological deterioration (NIHSS ≤3) occurred in 9/54 patients. New ischaemic lesions were detected in 21/24 patients who underwent MRI. Larger infarct volume was significantly associated with neurological deterioration.
Cerebral embolisation is immanent to TEER-MV and predominantly occurs during device interaction with the MV. Improvements to the procedure may focus on this procedural step.
IMPORTANCE The modest effects of clinical studies using intracoronary administration of autologous bone marrow–derived mononuclear cells (BMCs) in patients with chronic postinfarction heart failure ...may be attributed to impaired homing of BMCs to the target area. Extracorporeal shock wave treatment has been experimentally shown to increase homing factors in the target tissue, resulting in enhanced retention of applied BMCs. OBJECTIVE To test the hypothesis that targeted cardiac shock wave pretreatment with subsequent application of BMCs improves recovery of left ventricular ejection fraction (LVEF) in patients with chronic heart failure. DESIGN, SETTING, AND PARTICIPANTS The CELLWAVE double-blind, randomized, placebo-controlled trial conducted among patients with chronic heart failure treated at Goethe University Frankfurt, Germany, between 2006 and 2011. INTERVENTIONS Single-blind low-dose (n = 42), high-dose (n = 40), or placebo (n = 21) shock wave pretreatment targeted to the left ventricular anterior wall. Twenty-four hours later, patients receiving shock wave pretreatment were randomized to receive double-blind intracoronary infusion of BMCs or placebo, and patients receiving placebo shock wave received intracoronary infusion of BMCs. MAIN OUTCOMES AND MEASURES Primary end point was change in LVEF from baseline to 4 months in the pooled groups shock wave + placebo infusion vs shock wave + BMCs; secondary end points included regional left ventricular function assessed by magnetic resonance imaging and clinical events. RESULTS The primary end point was significantly improved in the shock wave + BMCs group (absolute change in LVEF, 3.2% 95% CI, 2.0% to 4.4%), compared with the shock wave + placebo infusion group (1.0% 95% CI, −0.3% to 2.2%) (P = .02). Regional wall thickening improved significantly in the shock wave + BMCs group (3.6% 95% CI, 2.0% to 5.2%) but not in the shock wave + placebo infusion group (0.5% 95% CI, −1.2% to 2.1%) (P = .01). Overall occurrence of major adverse cardiac events was significantly less frequent in the shock wave + BMCs group (n = 32 events) compared with the placebo shock wave + BMCs (n = 18) and shock wave + placebo infusion (n = 61) groups (hazard ratio, 0.58 95% CI, 0.40-0.85; P = .02). CONCLUSIONS AND RELEVANCE Among patients with postinfarction chronic heart failure, shock wave–facilitated intracoronary administration of BMCs vs shock wave treatment alone resulted in a significant, albeit modest, improvement in LVEF at 4 months. Determining whether the increase in contractile function will translate into improved clinical outcomes requires confirmation in larger clinical end point trials. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00326989
Aims
We investigated the implementation of new guidelines in ST-segment elevation myocardial infarction (STEMI) patients in a large real-world patient population in the metropolitan area of Berlin ...(Germany) over a 20-year period.
Methods
From January 2000 to December 2019, a total of 25 792 patients were admitted with STEMI to one of the 34 member hospitals of the Berlin-Brandenburg Myocardial Infarction Registry (B2HIR) and were stratified for sex and age < 75 and ≥ 75 years.
Results
The median age of women was 72 years (IQR 61–81) compared to 61 years in men (IQR 51–71). PCI treatment as a standard of care was implemented in men earlier than in women across all age groups. It took two years from the 2017 class IA ESC STEMI guideline recommendation to prefer the radial access route rather than femoral until > 60% of patients were treated accordingly. In 2019, less than 60% of elderly women were treated via a radial access. While the majority of patients < 75 years already received ticagrelor or prasugrel as antiplatelet agent in the year of the class IA ESC STEMI guideline recommendation in 2012, men ≥ 75 years lagged two years and women ≥ 75 three years behind. Amongst the elderly, in-hospital mortality was 22.6% (737) for women and 17.3% (523) for men (
p
< 0.001). In patients < 75 years fatal outcome was less likely with 7.2% (305) in women and 5.8% (833) in men (
p
< 0.001). After adjustment for confounding variables, female sex was an independent predictor of in-hospital mortality in patients ≥ 75 years (OR 1.37, 95% CI 1.12–1.68,
p
= 0.002), but not in patients < 75 years (
p
= 0.076).
Conclusion
In-hospital mortality differs considerably by age and sex and remains highest in elderly patients and in particular in elderly females. In these patient groups, guideline recommended therapies were implemented with a significant delay.
Graphical abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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