Stent thrombosis (ST) is a serious complication following coronary stenting. Intravascular optical coherence tomography (OCT) may provide insights into mechanistic processes leading to ST. We ...performed a prospective, multicenter study to evaluate OCT findings in patients with ST.
Consecutive patients presenting with ST were prospectively enrolled in a registry by using a centralized telephone registration system. After angiographic confirmation of ST, OCT imaging of the culprit vessel was performed with frequency domain OCT. Clinical data were collected according to a standardized protocol. OCT acquisitions were analyzed at a core laboratory. Dominant and contributing findings were adjudicated by an imaging adjudication committee.
Two hundred thirty-one patients presenting with ST underwent OCT imaging; 14 (6.1%) had image quality precluding further analysis. Of the remaining patients, 62 (28.6%) and 155 (71.4%) presented with early and late/very late ST, respectively. The underlying stent type was a new-generation drug-eluting stent in 50.3%. Mean reference vessel diameter was 2.9±0.6 mm and mean reference vessel area was 6.8±2.6 mm
. Stent underexpansion (stent expansion index <0.8) was observed in 44.4% of patients. The predicted average probability (95% confidence interval) that any frame had uncovered (or thrombus-covered) struts was 99.3% (96.1-99.9), 96.6% (92.4-98.5), 34.3% (15.0-60.7), and 9.6% (6.2-14.5) and malapposed struts was 21.8% (8.4-45.6), 8.5% (4.6-15.3), 6.7% (2.5-16.3), and 2.0% (1.2-3.3) for acute, subacute, late, and very late ST, respectively. The most common dominant finding adjudicated for acute ST was uncovered struts (66.7% of cases); for subacute ST, the most common dominant finding was uncovered struts (61.7%) and underexpansion (25.5%); for late ST, the most common dominant finding was uncovered struts (33.3%) and severe restenosis (19.1%); and for very late ST, the most common dominant finding was neoatherosclerosis (31.3%) and uncovered struts (20.2%). In patients presenting very late ST, uncovered stent struts were a common dominant finding in drug-eluting stents, and neoatherosclerosis was a common dominant finding in bare metal stents.
In patients with ST, uncovered and malapposed struts were frequently observed with the incidence of both decreasing with longer time intervals between stent implantation and presentation. The most frequent dominant observation varied according to time intervals from index stenting: uncovered struts and underexpansion in acute/subacute ST and neoatherosclerosis and uncovered struts in late/very late ST.
The hypertrophy of vascular smooth muscle cells as well as neointimal proliferation is critical in vascular remodeling, whereas leptin has proved to play an important role recently. The aim of the ...study was to investigate possible associations of two common leptin gene polymorphisms with restenosis after percutaneous coronary intervention (PCI). To study the association of two promoter polymorphisms, LEP -2548 G/A and LEP -188 C/A (dbSNP ID rs7799039 and rs791620) with neointimal proliferation in humans, 98 consecutive patients undergoing stenting into small coronary arteries (<3 mm) were genotyped. After a 6-month follow-up, the restenosis rate was estimated. Restenosis >50% occurred in 33.3% of patients carrying both A alleles, 33.3% of carriers of A and C alleles, and 31.4% of carriers of two CC alleles of LEP -188 C/A polymorphism; and in 25.0% of patients with AA, 32.7% with AG, and 30.4% with GG genotype of LEP -2548 G/A polymorphism. Interestingly, the heterozygote AG genotype of LEP -2548 polymorphism represented a highly significant risk for multiple-vessel disease when compared to both homozygote genotypes AA/GG (odds ratio = 4.038, 95% confidence interval: 1.732-9.465, P(corr) = 0.001). Based on our findings, the AG genotype of LEP -2548 G/A polymorphism might be considered a genetic marker for multiple-vessel disease but not for restenosis after PCI. The role of the leptin gene polymorphisms as genetic markers of restenosis will require further investigation to elucidate the underlying pathophysiological consequences.
Coronary angiography is still the most widely used method for the assessment of lumen of coronary arteries and for diagnosis and treatment of coronary artery disease. New imaging modalities of ...coronary arteries play an increasing role in interventional cardiology. Intravascular ultrasound (IVUS) is the oldest technology, however due to its high tissue penetration remains very important for imaging of left main coronary artery and saphenous vein grafts. IVUS was used in many clinical trials and clinical experience with it is huge. Optical coherence tomography (OCT) is a new, very fast developing method. It has ten times higher axial resolution than IVUS. It gives us the opportunity to assess the inner structures of coronary artery wall, to evaluate the characteristics of atherosclerotic plaques, quality of stent implantation and its healing. It helps us to find the culprit lesion of acute coronary syndrome in some cases, to diagnose the cause of stent thrombosis, and to evaluate stent apposition which has a direct relation to prognosis. We use it to perform complex percutaneous coronary interventions and after heart transplantation to diagnose the vascular graft disease. We strongly believe that OCT is important for the assessment of plaque instability and patient´s prognosis. Near infrared spectroscopy combined with IVUS can distinguish fibrous from lipid core plaques. Lipid core burden index is in relation to a risk of periprocedural myocardial infarction and to prognosis. It is the only method which can sufficiently detect the amount of lipids in coronary wall.
This study used optical coherence tomography to investigate the mechanism of false lumen (FL) formation in spontaneous coronary artery dissection (SCAD) by studying: 1) differences between ...fenestrated and nonfenestrated SCAD; 2) vasa vasorum density; and 3) light attenuation characteristics of the FL.
SCAD is an increasingly recognized cause of acute coronary syndromes, characterized by FL formation and compression of the true lumen (TL). The mechanisms underlying FL formation remain poorly understood.
A total of 65 SCAD patients (68 vessels) who underwent acute OCT imaging as part of routine clinical care were included. Images were classified by the absence or presence of a connection (fenestration) between the TL and FL. Indexed measurements of TL stenosis, external elastic lamina (EEL) area, FL area, and light attenuation of the FL were assessed. Vasa vasorum densities of SCAD cases were compared with those in control non-SCAD myocardial infarction cases.
In nonfenestrated cases, there was significantly larger expansion of the EEL area (9.1% vs. -1.9%; p <0.05) and a larger FL area (73.6% vs. 53.2%, respectively; p <0.05) in dissected segments. No significant differences were found between vasa vasorum density in SCAD and those in control subjects. The FL contents were heterogeneous but attenuated less light than whole blood or thrombus (4.28 ± 0.55 mm
vs. 5.08 ± 0.56 mm
; p < 0.05; vs. 4.96 ± 0.56 mm
; p < 0.05).
These observational data suggest that the absence of a fenestration leads to increased FL pressure and compression of the TL. Although vasa vasorum may still be implicated in pathogenesis, increased vasa vasorum density could be an epiphenomenon of vascular healing.
Observational and small, randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease.
We conducted an investigator-initiated, ...randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infarction (MI; 99.7% of patients) or high-risk stable coronary heart disease (0.3%). The primary end point was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary end points: all-cause death, cardiovascular death, MI, and stent thrombosis.
Because of the COVID-19 pandemic, the data safety and monitoring board recommended to halt the trial before attaining the prespecified sample size. Between October 1, 2016, and March 1, 2020, 2571 participants were randomized at 30 centers across 8 countries. Participants assigned to influenza vaccine totaled 1290 and individuals assigned to placebo equaled 1281; of these, 2532 received the study treatment (1272 influenza vaccine and 1260 placebo) and were included in the modified intention to treat analysis. Over the 12-month follow-up, the primary outcome occurred in 67 participants (5.3%) assigned influenza vaccine and 91 participants (7.2%) assigned placebo (hazard ratio, 0.72 95% CI, 0.52-0.99;
=0.040). Rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59 95% CI, 0.39-0.89;
=0.010), rates of cardiovascular death were 2.7% and 4.5%, (hazard ratio, 0.59 95% CI, 0.39-0.90;
=0.014), and rates of MI were 2.0% and 2.4% (hazard ratio, 0.86 95% CI, 0.50-1.46;
=0.57) in the influenza vaccine and placebo groups, respectively.
Influenza vaccination early after an MI or in high-risk coronary heart disease resulted in a lower risk of a composite of all-cause death, MI, or stent thrombosis, and a lower risk of all-cause death and cardiovascular death, as well, at 12 months compared with placebo. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02831608.
Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and ...could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI.
The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300–600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290.
Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio OR 0·97, 95% CI 0·80–1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 11% of 941 patients in the ticagrelor group vs 71 8% of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12–2·11; p=0·0070).
Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI.
ACTION Study Group and AstraZeneca.
Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with ...superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.
•Magnetic stent-grafts were made from 2205 steel stents and polyurethane nanofibers.•Stent-grafts remained patent and formed a thin and uniform neointima when implanted.•Stent-grafts captured endothelial cells labeled with magnetic nanoparticles.•Device refinements are needed in order to improve endothelial cell capture.
Yes-associated protein 1 (YAP1) is a transcriptional co-activator downstream of Hippo pathway. The pathway exerts crucial roles in organogenesis and its dysregulation is associated with the spreading ...of different cancer types. YAP1 gene encodes for multiple protein isoforms, whose specific functions are not well defined. We demonstrate the splicing of isoform-specific mRNAs is controlled in a stage- and tissue-specific fashion. We designed expression vectors encoding for the most-represented isoforms of YAP1 with either one or two WW domains and studied their specific signaling activities in YAP1 knock-out cell lines. YAP1 isoforms display both common and unique functions and activate distinct transcriptional programs, as the result of their unique protein interactomes. By generating TEAD-based transcriptional reporter cell lines, we demonstrate individual YAP1 isoforms display unique effects on cell proliferation and differentiation. Finally, we illustrate the complexity of the regulation of Hippo-YAP1 effector in physiological and in pathological conditions of the heart.
•YAP1 is known as an oncogene involved in the spreading of multiple cancer types.•The splicing of isoform-specific Yap1 mRNAs is controlled in a stage- and tissue-specific fashion.•CRISPR/Cas9 complementation highlights specific protein interactors and unique transcriptional activities for YAP1 isoforms.•Individual YAP1 isoforms display unique effects on cell proliferation and differentiation.•The splicing of isoform-specific Yap1 mRNAs is altered in cardiac pathologies.
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