Publications

<b>Background:</b> COVID-19 is associated with long-term risk of cardiovascular disease (CVD), particularly after severe disease. The long-term consequences of SARS-CoV-2 infection on endothelium are poorly understood. Senescent endothelial cells are dysfunctional, exhibit a proinflammatory 'senescence-associated-secretory-phenotype' (SASP) and promote CVD. We hypothesised that endothelium post-COVID is senescent and dysfunctional, promoting cardiovascular comorbidities. <b>Methods:</b> Endothelial colony forming cells (ECFC) are circulating endothelial progenitors and provide non-invasive access to endothelial cells. We collected blood samples from individuals who recovered from COVID-19 (n=6, 8-13 months post infection, 5 had critical disease) and age-matched healthy controls for ECFC isolation. ECFC were characterised for endothelial markers, proliferation, senescence and selected SASP mediators by immunofluorescence (IF). We used a high-throughput 'organ-on-a-chip' microfluidic platform (OrganoPlate-MIMETAS) that allows formation of microvessels for functional and IF analysis. <b>Results:</b> Post-COVID ECFC exhibited reduced proliferation (Ki-67), increased expression of senescence markers (senescence-associated-β-galactosidase activity, p21), IFN-γ-inducible-protein-10, plasminogen activator inhibitor-1 and von Willebrand Factor compared to control ECFC. In 3D cultures maintained for 14 days, microvessels formed with post-COVID ECFC showed increased permeability and disruption of endothelial junctions. <b>Conclusion:</b> We demonstrate that ECFC from patients post-COVID exhibit a dysfunctional, senescent and prothrombotic phenotype that may contribute to the increased risk of cardiovascular comorbidities.

Sirolimus-eluting stent (SES) implantation has been shown to reduce repeat revascularization in various randomized trials. The present study evaluated the outcomes after SES implantation in 46 octogenarian patients. SES implantation in octogenarians appears to be feasible and is associated with very small subsequent need for repeat target vessel revascularization at 1 year.

We compared the measurement of aortic leaflet calcification on contrast and non-contrast MSCT and investigated predictors of the need for balloon post-dilatation after TAVI.In 110 patients, who had TAVI with a Medtronic CoreValve prosthesis (MCS) for symptomatic aortic stenosis, calcification of the aortic root was measured on non-contrast MSCT (conventionally) and on contrast MSCT (signal attenuation >450 Houndsfield units). Calcium volume was underestimated on contrast- when compared to non-contrast MSCT: median (IQ-range)=759 (466 to 1295) vs. 2016 (1376 to 3262) and the difference between the two methods increased with higher calcium volumes (correlation coefficient r=0.90). Calcium mass was only slightly underestimated on contrast vs. non-contrast MSCT: median (IQ-range)=441 (268 to 809) vs. 555 (341 to 950) and there was no association between the differences and increasing calcium mass (r=0.17). Balloon post-dilatation was performed for significant aortic regurgitation after TAVI in 11 of 110 patients. When compared to controls, the patients who required balloon post-dilatation had higher aortic leaflet calcium on contrast CT (p<0.01), higher aortic annulus diameters (p<0.01) and higher annulus to prosthesis area ratio (p=0.01). ROC curves demonstrated that aortic root or aortic leaflet calcium measured on either contrast- or non-contrast MSCT showed excellent discrimination for the requirement of balloon post-dilatation (area under ROC >0.80 for all), whereas the discriminatory value of aortic annulus dimensions was moderate (area under ROC=0.69) and that of prosthesis to annulus ratio was poor (area under ROC=0.36).Dense aortic leaflet calcification measured on contrast MSCT discerned well the need for balloon post-dilatation after TAVI with an MCS for significant PAR. Non-contrast MSCT may no longer be needed to quantify aortic root calcium before TAVI.

<h3>OBJECTIVE</h3> To describe the long term clinical outcome (up to 11 years) after coronary stenting. <h3>DESIGN</h3> A single centre observational study encompassing 1000 consecutive patients with a first stent implantation (1560 stents) between 1986 and 1996, who were followed for at least one year with a median follow up of 29 months (range 12–132 months). <h3>RESULTS</h3> Up to July 1997 the cumulative incidence of the major adverse cardiac events (MACE) of death, non-fatal acute myocardial infarction, coronary artery bypass grafting, and repeat percutaneous transluminal coronary angioplasty was 8.2%, 12.8%, 13.1%, and 22.4%, respectively. Survival at one, three, and five years was 95%, 91%, and 86%, respectively. Comparison of MACE incidence during the "anticoagulant era" and the "ticlopidine era" revealed significantly improved event free survival with ticlopidine (27% <i>v</i>13%; p &lt; 0.005). Multivariable analyses showed that ejection fraction &lt; 50% (relative risk (RR) 4.1), multivessel disease (RR 3.0), diabetes (RR 2.9), implantation in saphenous vein graft (RR 2.1), indication for unstable angina (RR 1.9), and female sex (RR 1.7) were independent predictors of increased mortality after stenting. Independent predictors of any MACE were multivessel stenting (RR 2.0), implantation in saphenous bypass graft (RR 1.6), diabetes (RR 1.5), anticoagulant treatment (versus ticlopidine and aspirin) (RR 1.5), bailout stenting (RR 1.5), multivessel disease (RR 1.4), and multiple stent implantation (RR 1.5). <h3>CONCLUSIONS</h3> Long term survival and infarct free survival was good, particularly in non-diabetic men with single vessel disease and good ventricular function, who had a single stent implanted in a native coronary artery. A dramatic improvement was observed in event free survival, both early and late, with the replacement of anticoagulation by ticlopidine. This, of course, cannot be separated from improved stent implantation techniques between 1986 and 1995. Ultimately, almost 40% of the patients experienced an adverse cardiac event (mainly repeat intervention) in the long term. New advances in restenosis treatments and in secondary prevention must be directed at this aspect of patient management after stenting.

No abstract is provided for this article.

Critically evaluating the methodology of the adventitial delivery of stem cells, some specific options should be underlined. Adventitia as the most superficial layer, consisting of connective tissue has to be distinguished of perivascular tissues. By strict definition, an adventitia is the outermost connective tissue covering any organ, or vessel. The “adventitial” delivery of stem cells with a 1mm micro-needle means a delivery to superficial so called pericardial myocardium, perivascular fat tissues, including a risk of perforation and injury of soft tissues. In fact, the mapping of the artery with visualization of the three-layer vessel structure and perivascular tissues as well as pericardial space with the state-of-the-art imaging approaches including IVUS (intravascular ultrasound) or OCT (optical coherence tomography) allows to find an optimal site for injection, prevents any technical complications and improves efficacy. NOGA magnetic navigation system still remains the optimal tool for the stem cell delivery to myocardium with appropriate visualization of necrosis and peri-infarct tissues. Potentially, more advanced imaging provides a chance to deliver infusate to the adventitial layer, which is a gate to the vessel wall for inflammation as well as a source of stem and progenitor cells, and myofibroblasts.

No abstract is provided for this article.

To assess the fate of incomplete stent apposition (ISA) after deployment of sirolimus-eluting stents (SESs). Thirty-two patients having intravascular ultrasound (IVUS)-guided PCI with SESs underwent assessment of stent deployment with quantitative coronary angiography, IVUS, and optical coherence tomography (OCT) pre-procedure, post-procedure, and at 10 months follow-up. Incomplete stent apposition was defined as separation of a stent strut from the inner vessel wall by >160 µm. At follow-up, 4.67% of struts with ISA at deployment failed to heal and 7.59% which were well apposed did not develop neointimal hyperplasia even after 10 months. Lesion remodelling was responsible for the development of late ISA in only 0.37% of struts. Failure of adequate neointimal hyperplasia was quantitatively the most important mechanism responsible for persistent acute ISA, classified in previous studies, which relied only on follow-up OCT, as late ISA. Thrombus was visualized in 20.6% of struts with ISA at follow-up and in 2.0% of struts with a good apposition (P < 0.001). In patients with SESs, ISA can fail to heal and even complete apposition can be associated with no neointimal hyperplasia. Incomplete stent apposition without neointimal hyperplasia was significantly associated with the presence of OCT-detected thrombus at follow-up, and may constitute a potent substrate for late stent thrombosis.

The miniaturization of medical devices and the progress in image processing have allowed the development of a multitude of intravascular imaging modalities that permit more meticulous examination of coronary pathology. However, these techniques have significant inherent limitations that do not allow a complete and thorough assessment of coronary anatomy. To overcome these drawbacks, fusion of different invasive and noninvasive imaging modalities has been proposed. This integration has provided models that give a more detailed understanding of coronary artery pathology and have proved useful in the study of the atherosclerotic process. In this review, the authors describe the currently available hybrid imaging approaches, discuss the technological innovations and efficient algorithms that have been developed to integrate information provided by different invasive techniques, and stress the advantages of the obtained models and their potential in the study of coronary atherosclerosis.