New Technologies for the Treatment of Coronary and Structural Heart Diseases

There has been significant progress in the field of interventional cardiology, from the development of newer devices to newer applications of technology, resulting in improved cardiovascular outcomes. The goal of this Special Issue is to update practicing clinicians and provide a comprehensive collection of original articles, reviews, and editorials. To this end, we invited state-of-the-art reviews, including reviews of new technology and therapeutics, as well as original research in this area to be considered for inclusion in this issue. Examples include the history and evolution of interventional techniques, reviews of specific devices and technologies for coronary artery disease (i.e., stent technology, atherectomy devices, coronary physiology, intracoronary imaging, and robotics), structural heart diseases (i.e., ASD: atrial septal defect; LAAC: left atrial appendage closure; MC: MitraClip; PFO: patent foramen ovale; TAVI: transcatheter aortic valve implantation), advances in the management of challenging coronary anatomy, new biomarkers of cardiovascular disease (noncoding RNAs, etc.), and interventional techniques in the management of heart failure, peripheral arterial diseases, and pulmonary embolism. This Special Issue presents the most recent advances in the field of coronary and structural heart diseases as well as their implications for future patient care

Added value of acute multimodal CT-based imaging (MCTI) : a comprehensive analysis

Introduction: MCTI is used to assess acute ischemic stroke (AIS) patients.We postulated that use of MCTI improves patient outcome regardingindependence and mortality.Methods: From the ASTRAL registry, all patients with an AIS and a non-contrast-CT (NCCT), angio-CT (CTA) or perfusion-CT (CTP) within24 h from onset were included. Demographic, clinical, biological, radio-logical, and follow-up caracteristics were collected. Significant predictorsof MCTI use were fitted in a multivariate analysis. Patients undergoingCTA or CTA&CTP were compared with NCCT patients with regards tofavourable outcome (mRS ≤ 2) at 3 months, 12 months mortality, strokemechanism, short-term renal function, use of ancillary diagnostic tests,duration of hospitalization and 12 months stroke recurrence

Generating Reliable and Responsive Observational Evidence: Reducing Pre-analysis Bias

A growing body of evidence generated from observational data has demonstrated the potential to influence decision-making and improve patient outcomes. For observational evidence to be actionable, however, it must be generated reliably and in a timely manner. Large distributed observational data networks enable research on diverse patient populations at scale and develop new sound methods to improve reproducibility and robustness of real-world evidence. Nevertheless, the problems of generalizability, portability and scalability persist and compound. As analytical methods only partially address bias, reliable observational research (especially in networks) must address the bias at the design stage (i.e., pre-analysis bias) including the strategies for identifying patients of interest and defining comparators. This thesis synthesizes and enumerates a set of challenges to addressing pre-analysis bias in observational studies and presents mixed-methods approaches and informatics solutions for overcoming a number of those obstacles. We develop frameworks, methods and tools for scalable and reliable phenotyping including data source granularity estimation, comprehensive concept set selection, index date specification, and structured data-based patient review for phenotype evaluation. We cover the research on potential bias in the unexposed comparator definition including systematic background rates estimation and interpretation, and definition and evaluation of the unexposed comparator. We propose that the use of standardized approaches and methods as described in this thesis not only improves reliability but also increases responsiveness of observational evidence. To test this hypothesis, we designed and piloted a Data Consult Service - a service that generates new on-demand evidence at the bedside. We demonstrate that it is feasible to generate reliable evidence to address clinicians’ information needs in a robust and timely fashion and provide our analysis of the current limitations and future steps needed to scale such a service

Towards rational treatments in subarachnoid haemorrhage

This thesis investigates two equivocal treatment strategies in subarachnoid haemorrhage (SAH). The first is administration of tranexamic acid (TXA), previously shown to have no beneficial effect on the clinical outcome. In three studies we investigate whether TXA is beneficial in a subgroup of patients (patients with a proven ruptured aneurysm; using different timing intervals from ictus to TXA treatment; good-grade and poor-grade aneurysmal SAH). None of the subgroup analyses shows a beneficial effect of TXA on clinical outcome. The second strategy is hypertension-induction, a non-evidence-based, though worldwide applied, treatment of delayed cerebral ischemia (DCI). The results show that hypertension-induction more frequently leads to clinical improvement on day one after DCI, however, improvement rates were similar on day five, due to spontaneous reversal of DCI-symptoms in patients treated without hypertension-induction. Clinical outcome also did not differ between both groups after three or six months. Part two focuses on biomarkers of DCI. An extensive literature review resulted in a selection of seven promising biomarkers of clinical DCI (haptoglobin polymorphism 2-1 and 2-2, ADAMTS13, neutrophil/lymphocyte ratio, P-selectin and von Willebrand Factor in blood; and F2-isoprostane in urine), and one biomarker of radiological DCI (lactate/pyruvate ratio in microdialysate). The combination of a review on viscoelastic testing in SAH patients and our prospective study on rotational thromboelastometry (ROTEM) in aneurysmal SAH showed that hypercoagulability, as detected by ROTEM, has good predictive test characteristics for DCI and excellent predictive test characteristics for poor clinical outcome. Lastly, we show that platelet RNA profiles significantly differ between patients with and without radiological DCI, and selected a radiological DCI-specific 13 platelet RNA panel, which was already apparent within the first 24 hours after SAH