A new approach for improving coronary plaque component analysis based on intravascular ultrasound images

Virtual histology intravascular ultrasound (VH-IVUS) is a clinically available technique for atherosclerosis plaque characterization. It, however, suffers from a poor longitudinal resolution due to electrocardiogram (ECG)-gated acquisition. This article presents an effective algorithm for IVUS image-based histology to overcome this limitation. After plaque area extraction within an input IVUS image, a textural analysis procedure consisting of feature extraction and classification steps is proposed. The pixels of the extracted plaque area excluding the shadow region were classified into one of the three plaque components of fibro-fatty (FF), calcification (CA) or necrotic core (NC) tissues. The average classification accuracy for pixel and region based validations is 75% and 87% respectively. Sensitivities (specificities) were 79% (85%) for CA, 81% (90%) for FF and 52% (82%) for NC. The kappa (kappa) = 0.61 and p value = 0.02 indicate good agreement of the proposed method with VH images. Finally, the enhancement in the longitudinal resolution was evaluated by reconstructing the IVUS images between the two sequential IVUS-VH images

Manifold learning for image-based gating of intravascular ultrasound(IVUS) pullback sequences

Intravascular Ultrasound(IVUS) is an imaging technology which provides cross-sectional images of internal coronary vessel struc- tures. The IVUS frames are acquired by pulling the catheter back with a motor running at a constant speed. However, during the pullback, some artifacts occur due to the beating heart. These artifacts cause inaccu- rate measurements for total vessel and lumen volume and limitation for further processing. Elimination of these artifacts are possible with an ECG (electrocardiogram) signal, which determines the time interval cor- responding to a particular phase of the cardiac cycle. However, using ECG signal requires a special gating unit, which causes loss of impor- tant information about the vessel, and furthermore, ECG gating function may not be available in all clinical systems. To address this problem, we propose an image-based gating technique based on manifold learning. Quantitative tests are performed on 3 different patients, 6 different pull- backs and 24 different vessel cuts. In order to validate our method, the results of our method are compared to those of ECG-Gating method

Angiotensin-converting enzyme insertion/deletion polymorphism does not influence the restenosis rate after coronary stent implantation

Background. Experimental studies have shown an activation of the angiotensin-converting enzyme (ACE) system as a response to endothelial injury. Recent publications have elucidated the hypothesis that the ACE gene polymorphism may influence the level of late luminal loss after coronary stent implantation. It is still unclear whether the polymorphism of the angiotensin gene is a major predictor of the extent of neointimal hyperplasia. In this multicenter study, we therefore tested the relationship between the ACE gene polymorphism and the restenosis rate after coronary stent implantation. Methods: As a substudy of the optimization with intracoronary, ultrasound (ICUS) to reduce stent restenosis (OPTICUS) study, we analyzed ACE serum levels and the ACE gene polymorphism in 154 patients at 9 different centers. All patients underwent elective coronary stent implantation in a stenosis of a major coronary vessel. Balloon inflations were repeated until a satisfactory result was achieved in on-line quantitative coronary angiography or ICUS fulfilling the OPTICUS study criteria. After follow-up of 6 months, all patients underwent reangiography tinder identical projections as the baseline procedure. A blinded quantitative analysis of the initial procedure as well as the follow-up examinations were performed by an independent core laboratory. ACE gene polymorphism and ACE serum activity were measured at the 6-month follow-up in a double-blinded setting. Results: With respect to the ACE gene polymorphism, there were three subgroups: DID genotype (48 patients), ID (83 patients) and 11 (23 patients). The subgroups did not differ in regard to age, gender, extent of coronary artery disease, stenosis length, initial degree of stenosis or degree of stenosis after stent implantation. In all, 39 patients (25.3%) had significant restenosis: 12 DD patients (25.0%), 18 ID patients (21.7%) and 9 II patients (39.1%) (odds ratio 2.164, 95% confidence interval 0.853-5.493). We obtained the following results for ACE serum levels: 0.53 mumol/l/s in the DD subgroup, 0.29 mumol/l/s in the ID

Coronary Computed Tomography Angiography Based Assessment of Endothelial Shear Stress and Its Association with Atherosclerotic Plaque Distribution In-Vivo

Purpose The relationship between low endothelial shear stress (ESS) and coronary atherosclerosis is well established. ESS assessment so far depended on invasive procedures. The aim of this study was to demonstrate the relationship between ESS and coronary atherosclerosis by using non-invasive coronary computed tomography angiography (CTA) for computational fluid dynamics (CFD) simulations. Methods A total number of 7 consecutive patients with suspected coronary artery disease who received CTA and invasive angiography with IVUS analysis were included in this study. CTA examinations were performed using a dual-source scanner. These datasets were used to build a 3D mesh model. CFD calculations were performed using a validated CFD solver. The presence of plaque was assumed if the thickness of the intima-media complex exceeded 0.3 mm in IVUS. Plaque composition was derived by IVUS radiofrequency data analysis. Results Plaque was present in 32.1% of all analyzed cross-sections. Plaque prevalence was highest in areas of low ESS (49.6%) and high ESS (34.8%). In parts exposed to intermediate-low and intermediate-high ESS few plaques were found (20.0% and 24.0%) (p<0.001). Wall thickness was closely associated with local ESS. Intima-media thickness was 0.43 +/- 0.34mm in low and 0.38 +/- 0.32mm in high ESS segments. It was significantly lower when the arterial wall was exposed to intermediate ESS (0.25 +/- 0.18mm and 0.28 +/- 0.20mm) (p<0.001). Fibrofatty tissue was predominately found in areas exposed to low ESS (p <= 0.023). Conclusions In this study a close association of atherosclerotic plaque distribution and ESS pattern could be demonstrated in-vivo. Adding CFD analysis to coronary CTA offers the possibility to gather morphologic and physiologic data within one non-invasive examination

Do Acute Coronary Events Affect Lipid Management and Cholesterol Goal Attainment in Germany?

Objective To document utilization of lipid-lowering therapy, attainment of low-density lipoprotein cholesterol target values, and cardiovascular outcomes in patients hospitalized for acute coronary syndrome in Germany. Methods The Dyslipidemia International Study II was a multicenter, observational study of the prevalence of dyslipidemia and lipid target value attainment in patients surviving any acute coronary syndrome event. Among patients on lipid-lowering therapy for ≥3 months, use of lipid-lowering therapy and lipid profiles were assessed at admission and again at 120 ± 15 days after admission (the follow-up time point). Multivariate logistic regression was used to identify variables predictive of low-density lipoprotein cholesterol target value attainment in patients using lipid-lowering therapy. Results A total of 461 patients hospitalized for acute coronary syndrome were identified, 270 (58.6%) of whom were on lipid-lowering therapy at admission. Among patients on lipid-lowering therapy, 90.7% and 85.9% were receiving statin monotherapy at admission and follow-up, respectively. Mean (SD) lowdensity lipoprotein cholesterol levels in patients on lipid-lowering therapy were 101 (40) mg/dl and 95 (30) mg/dl at admission and follow-up, respectively. In patients with data at both admission and followup (n= 61), low-density lipoprotein cholesterol target value attainment rates were the same (19.7%) at both time points. Smoking was associated with a 77% lower likelihood of attaining the low-density lipoprotein cholesterol target value. Conclusion Hospitalization for an acute event does not greatly alter lipid management in acute coronary syndrome patients in Germany. Both lipid-lowering therapy doses and rates of low-density lipoprotein cholesterol target value attainment remained essentially the same several months after the event

Measurement of fractional flow reserve to guide decisions for percutaneous coronary intervention

Background Coronary artery disease (CAD) is one of the leading causes of premature death in Germany. Percutaneous coronary interventions (PCI) are frequently performed in patients with angiographically intermediate stenoses. However, the necessity of PCI has not been proven for all patients. Pressure-based fractional flow reserve (FFR) is an invasive test that can be used to assess the functional significance of intermediate coronary stenoses in order to guide decisions on PCI. Objectives This health technology assessment (HTA) aims to evaluate (1) the diagnostic accuracy, (2) the risk-benefit trade-off and (3) the long-term cost-effectiveness of FFR measurement to guide the decision on PCI in patients with stable angina pectoris and intermediate coronary stenoses. Methods We performed a literature search in medical and HTA databases. We used the DIMDI instruments (DIMDI = Deutsches Institut für Medizinische Dokumentation und Information/German Institute for Medical Information and Documentation) to assess study quality and to extract and summarize the information in evidence tables. We performed a meta-analysis to calculate the pooled overall estimate for sensitivity and specificity of FFR with 95% confidence intervals (95% CI). Individual studies' case numbers were used as weights. The influence of single studies and important covariates on the results was tested in sensitivity analyses. We developed the German Coronary Artery Disease Outcome Model (German CADOM), a decision-analytic Markov model, to estimate the long-term effectiveness and cost-effectiveness of FFR measurement in the context of the German healthcare system. Results Our literature search identified twelve studies relevant to this HTA-report including ten diagnostic accuracy studies of FFR measurement, one randomized clinical trial (RCT) investigating the clinical benefits of this technique as well as one economic evaluation. Pooled estimates for sensitivity and specificity were 81.7% (95% CI: 77.0-85.7%) and 78.7% (95% CI: 74.3-82.7%). Sensitivity analyses indicated robust results. The RCT investigating the efficacy of an FFR-based treatment strategy provided evidence of the advantages of this strategy for patients with respect to freedom from angina and major adverse cardiac events. The published cost-effectiveness study demonstrates that the FFR-based strategy is cost-saving in the US context. Based on our own decision analysis for the German context, the FFR-based strategy improves (quality-adjusted) life-expectancy when compared to universal PCI and is cost-effective in the German healthcare context. This HTA is limited by the use of poor gold standards in several of the included diagnostic studies as well as the ongoing advance of technology and treatment options in interventional cardiology. Results of the decision analysis are limited by the necessary underlying assumptions and the uncertainty regarding long-term mortality reduction associated with PCI. Further research should focus on the acquisition of long-term data for disease progression in patients with and without functional coronary stenoses as well as the benefits and risks of PCI. Conclusions Based on actual evidence and our decision analysis, the use of FFR measurement to guide the decision on PCI should lead to better short- and long-term clinical outcomes in patients with stable angina and single-vessel disease without documented myocardial ischemia and it should provide a cost-effective use of resources in the German healthcare system. FFR measurement should be introduced in routine clinical practice. However, appropriate reimbursement strategies are necessary to avoid wrong incentives.Hintergrund Die koronare Herzkrankheit gehört zu den wichtigsten Mortalitätsursachen in Deutschland. Es wird zunehmend bezweifelt, ob alle der zahlreich durchgeführten perkutanen Koronarinterventionen (PCI) bei angiographisch mittelgradigen Stenosen medizinisch sinnvoll und notwendig sind. Für die Abwägung von medizinischem Nutzen, Risiko und Kosten zwischen PCI und medikamentöser Behandlung kann die druckbasierte Messung der koronaren fraktionierten Flussreserve (FFR) eine wichtige Entscheidungshilfe sein. Ziele Dieses Health Technology Assessment (HTA) dient der Bewertung (1) der diagnostischen Genauigkeit, (2) der Nutzen-Risiko-Abschätzung und (3) der Langzeitkosteneffektivität der FFR zur Indikationsstellung der PCI bei stabiler Angina pectoris und angiographisch mittelgradigen Stenosen. Methoden Es erfolgte eine Literaturrecherche in medizinischen und HTA-Datenbanken. Relevante Literaturstellen wurden mit Hilfe des DIMDI-Instrumentariums (DIMDI = Deutsches Institut für Medizinische Dokumentation und Information) auf Studienqualität geprüft, die Ergebnisse wurden systematisch beschrieben und in Evidenztabellen zusammenfassend dargestellt. Im Rahmen einer Metaanalyse wurden die gepoolten Schätzer für Sensitivität und Spezifität der FFR mit 95%-Konfidenzintervallen (95% KI) berechnet. Potenzielle Einflussfaktoren der Testgüte wurden in Sensitivitätsanalysen untersucht. Für die Bestimmung der klinischen und gesundheitsökonomischen Langzeitkonsequenzen der FFR-Messung im Kontext des deutschen Gesundheitssystems wurde ein entscheidungsanalytisches Markov-Modell entwickelt, das German Coronary Artery Disease Outcome Model (German CADOM). Ergebnisse Die Literaturrecherche ergab insgesamt zwölf relevante Studien: zehn Studien zur diagnostischen Testgüte von FFR, eine randomisierte klinische Studie (RCT) zum medizinischen Nutzen und eine gesundheitsökonomische Evaluation. Die gepoolte Sensitivität von FFR beträgt 81,7% (95% KI: 77,0-85,7%), die gepoolte Spezifität 78,7% (95% KI: 74,3-82,7%). Sensitivitätsanalysen deuten auf robuste Ergebnisse hin. Das RCT zum klinischen Nutzen einer FFR-basierten Behandlungsstrategie zeigt Vorteile für Patienten hinsichtlich Anginafreiheit und schwerwiegender kardialer Ereignisse. Die publizierte gesundheitsökonomische Evaluation deutet darauf hin, dass die FFR-Messung im US-amerikanischen Kontext kostensparend ist. Basierend auf den Ergebnissen des deutschen Entscheidungsmodells (German CADOM) führt die FFR-basierte Strategie zu einer höheren (qualitätsadjustierten) Lebenserwartung und ist im Kontext des deutschen Gesundheitssystems kosteneffektiv. Dieser HTA-Bericht ist limitiert durch die Verwendung eingeschränkter Goldstandards in einigen diagnostischen Studien sowie durch die fortwährende Weiterentwicklung von Technologie und Behandlungsmöglichkeiten in der interventionellen Kardiologie. Die Aussagen der Entscheidungsanalyse werden eingeschränkt durch die verwendeten Annahmen und Unsicherheit zur Wirksamkeit der PCI bezüglich Langzeitmortalität. Forschungsbedarf besteht in der Erhebung und Auswertung von Langzeitdaten zur Krankheitsprogression bei Patienten mit und ohne funktioneller Stenose sowie zu Nutzen und Risiken der PCI. Schlussfolgerungen und Empfehlungen Basierend auf der aktuellen Evidenz und der entscheidungsanalytischen Modellierung ist davon auszugehen, dass bei Patienten mit stabiler Angina pectoris und Eingefäßerkrankung ohne kardialen Ischämienachweis die FFR-Messung zur Indikationsstellung der PCI zu verbesserten kurz- und langfristigen klinischen Ergebnissen führt sowie einen kosteneffektiven Einsatz von Ressourcen im deutschen Gesundheitssystem darstellt. Ein breiterer Einsatz der FFR-Messung erscheint sinnvoll, erfordert jedoch die Vereinbarung angemessener Entgelte zur Vermeidung möglicher Fehlanreize und Fehlsteuerungen

Pathogenic Fungi Regulate Immunity by Inducing Neutrophilic Myeloid-Derived Suppressor Cells

Peer reviewedPublisher PD

Whole brain radiation therapy alone versus radiosurgery for patients with 1–10 brain metastases from small cell lung cancer (ENCEPHALON Trial): study protocol for a randomized controlled trial

Background: Conventional whole brain radiotherapy (WBRT) has been established as the treatment standard in patients with cerebral metastases from small-cell lung cancer (SCLC), however, it has only modest efficacy and limited prospective data is available for WBRT as well as local treatments such as stereotactic radiosurgery (SRS). Methods/design: The present single-center prospective randomized study, conducted at Heidelberg University Hospital, compares neurocognitive function, as objectively measured by significant deterioration in Hopkins Verbal Learning Test – Revised total recall at 3 months. Fifty-six patients will be randomized to receive either SRS of all brain metastases (up to ten lesions) or WBRT. Secondary endpoints include intracranial progression (local tumor progression and number of new cerebral metastases), extracranial progression, overall survival, death due to brain metastases, local (neurological) progression-free survival, progression-free survival, changes in other cognitive performance measures, quality of life and toxicity. Discussion: Recent evidence suggests that SRS might be a promising treatment option for SCLC patients with brain metastases. The present trial is the first to prospectively investigate the treatment response, toxicity and neurocognition of WBRT and SRS in SCLC patients. Trial registration: Clinicaltrials.gov NCT03297788 . Registered September 29, 2017