Thrombotic Lesions Research Articles

P139 RETURN TO THE ORIGINS: WHEN THE THROMBOLYSIS SAVES THE ANGIOPLASTY

Abstract A 62 year old man arrived in PS for typical chest pain radiating to the jugular and associated with sweating for about three hours. History of arterial hypertension and untreated dyslipidemia, family history of CVD. ECG: sinus rithm at rate of 50 bpm with first degree AVB. Inferior ST elevation in inferior leads and ST depression in V2–V3. Echocardiogram: depressed systolic function (EF 48%) in relation to hypo–akinesia of the mid–basal segments of the inferior–posterior–lateral wall. Diagnosed with STEMI inferior–posterior, was sent to the cath lab to undergo to emergency coronary angiography, with findings of non–significant atheromas on IVA and Cx. Multiple unsuccessful attempts to search for the right coronary artery and failure to visualize the aortography in two complementary projections. During the procedure hemodynamic and electrical instability, worsening angor, marked hypotension and extreme bradycardia up to complete AVB with asystole phases. Inotropics and atropine were started, which proved ineffective, and it was therefore decided to proceed with the implantation of a temporary pacemaker. During the placement, the patient presented cardiac arrest from VF (likely an irritating effect from the passage of the lead through the tricuspid) treated with effective DC–shock. Given the technical difficulties in proceeding with mechanical revascularization and given the patient‘s instability, the decision was made to postpone PCI by attempting systemic thrombolysis. Early efficacy of thrombolysis with disappearance of precordial pain, improvement of echo motion and reduction > 50% of the ST–segment elevation to the rare spontaneous QRS displayed at the transient shutdown of the temporary PM. Subsequent emergence of AF at rate of 116 bpm. Approximately 12 hours after thrombolysis: complete ST resolution in absence of Q waves. AngioTC of the coronaries was performed which showed regularl origin of Cdx from the right coronary sinus but higher up and lateralized to the left, with severe lesion in the first segment. So the patient underwent falicitated PCI with detection of ostio–proximal Cdx thrombotic lesion effectively treated with PTCA and drug–eluting stent placement with good final angiographic result. Control echo: preserved global left ventricular motion (FE 55%), hypokinesia of the basal segment of the inferior wall. The remaining stay decurred without any complications and the patient was discharged with indications for a close follow–up.

Genetic, clinical, and pathological study of patients with severe hypertension-associated renal microangiopathy.

Severe hypertension may be a prominent manifestation of complement-mediated thrombotic microangiopathy. Furthermore, patients with severe hypertension-associated thrombotic microangiopathy may present with concurrent hematologic abnormalities that mimic complement-mediated thrombotic microangiopathy. Whether or not severe hypertension-associated thrombotic microangiopathy is associated with genetic susceptibility in complement- and/or coagulation-pathway genes remains unclear, and there is thus a need to identify clinicopathological clues to distinguish between these entities. Forty-five patients with concomitant severe hypertension and thrombotic microangiopathy on kidney biopsy were identified retrospectively. Whole-exome sequencing was performed to identify rare variants in 29 complement- and coagulation-cascade genes. Clinicopathological features were compared between patients with severe hypertension-associated thrombotic microangiopathy and complement-mediated thrombotic microangiopathy with severe hypertension. Three patients with pathogenic variants diagnostic of complement-mediated thrombotic microangiopathy and two with anti-factor H antibody positivity were diagnosed with complement-mediated thrombotic microangiopathy with severe hypertension. Among the 40 patients with severe hypertension-associated thrombotic microangiopathy, 53 rare variants of uncertain significance were found in the analyzed genes in 34 (34/40, 85%) patients, of whom 12 patients harbored two or more variants. Compared with complement-mediated thrombotic microangiopathy patients with severe hypertension, patients with severe hypertension-associated thrombotic microangiopathy were more likely to have left ventricular wall thickening (p < 0.001), less-severe acute glomerular thrombotic microangiopathy lesions including mesangiolysis and subendothelial space widening (both p < 0.001), and less arteriolar thrombosis formation (p < 0.001). Rare genetic variants involving complement and coagulation pathways can be found in patients with severe hypertension-associated thrombotic microangiopathy; their role needs further investigation. Cardiac remodeling and acute glomerular TMA lesions may help to differentiate between severe hypertension-associated thrombotic microangiopathy and complement-mediated thrombotic microangiopathy with severe hypertension.

Thrombus containing lesions strategies during primary percutaneous coronary interventions in ST-segment elevation myocardial infarction: insights from ORPKI National Registry

In the era of potent P2Y12 inhibitors, according to current guidelines, treatment with glycoprotein IIb/IIIa inhibitors (GPIs) should be limited to bail-out and/or highly thrombotic situations. Similarly, the recommendation for aspiration thrombectomy (AT) is downgraded to very selective use. We examine the prevalence, and predictors of GPI and AT use in STEMI patients referred to primary percutaneous coronary intervention (PCI). Data on 116,873 consecutive STEMI patients referred to primary PCI in Poland between 2015 and 2020 were analyzed. GPIs were administered in 29.3%, AT was used in 11.6%, and combined treatment with both in 6.1%. There was a mild trend toward a decrease in GPI and AT usage during the analyzed years. On the contrary, there was a rapid growth of the ticagrelor/prasugrel usage rate from 6.5 to 48.1%. Occluded infarct-related artery at baseline and no-reflow during PCI were the strongest predictors of GPI administration (OR 2.3; 95% CI 2.22–2.38 and OR 3.47; 95% CI 3.13–3.84, respectively) and combined usage of GPI and AT (OR 4.4; 95% CI 4.08–4.8 and OR 3.49; 95% CI 3.08–3.95 respectively) in a multivariate logistic regression model. Similarly, the administration of ticagrelor/prasugrel was an independent predictor of both adjunctive treatment strategies. In STEMI patients in Poland, GPIs are selectively used in one in four patients during primary PCI, and the combined usage of GPI and AT is marginal. Despite the rapid growth in potent P2Y12 inhibitors usage in recent years, GPIs are selectively used at a stable rate during PCI in highly thrombotic lesions.

Ischemic Stroke with Anticoagulant Protein C Deficiency

Ischemic stroke is a circulatory disorder in brain is caused by reduced or stopped blood flow in some areas of brain. It can be caused by thrombotic lesions resulting from atherosclerosis and by emboli that have detached from the lesions atherosclerosis in the heart or cerebral arteries. Ischemic stroke category consists of emboli and lacunae. Characteristic profile clinical manifestations of acute embolic stroke are sudden onset with maximal neurologic deficits. Embolic often originate from heart or from ulcerative carotid plaques. Atrial fibrillation is a predisposing factor for cardiac thrombus, associated with six times of risk increase in strokes. The patient had a diagnosis with a clinical description of a history of post cerebrovascular disorder non hemorrhagic (CVD-NH/ischemic stroke) with hypercoagulable state from an outpatient clinic on April 13th, 2016 for examination antithrombin III (AT III), protein C, protein S, ACA IgG, ACA IgM, fibrinogen, D-dimer, and INR.

Minimal vessel area predicts in-stent restenosis in nonthrombotic iliac vein compression syndrome after stenting.

Minimal vessel area predicts in-stent restenosis in nonthrombotic iliac vein compression syndrome after stenting.

Precision Navigation of Venous Thrombosis Guided by Viscosity-Activatable Near-Infrared Fluorescence.

Thrombus are blood clots formed by abnormal hemostasis in blood vessels and are closely associated with various diseases such as pulmonary embolism, myocardial infarction and stroke. Early diagnosis and treatment of thrombus is the key to reducing the high risk of thrombotic disease. Given that early thrombus is small in early size, free instability, wide regional distribution and fast formation, it is urgent to develop all-inclusive detection methods that combine high signal-to-noise ratio, in situ dynamic and rapid in-depth tissue imaging. Near-infrared (NIR) fluorescence imaging, with its excellent high spatiotemporal resolution and tissue penetration depth, is a powerful technique for direct visualization of thrombotic events in situ. Considering the fibrin highly expressed in the thrombus is a typical thrombotic target. Moreover, the viscosity of the thrombus is markedly higher than its surroundings. Therefore, we developed a fibrin-targeting and viscosity-activating thrombus NIR fluorescent probe (TIR-V) for high-resolution and high-sensitivity in situ lighten-up thrombus. TIR-V has the advantages of good thrombus targeting, significant "off-on" fluorescence specific response to viscosity, bright NIR fluorescence and good biocompatibility. The thrombus is clearly delineated by a high signal-to-noise ratio NIR fluorescence imaging, enabling imaging detection and precise navigation of thrombotic regions. This work demonstrates the potential of TIR-V as a bifunctional probe for definitive diagnostic imaging and direct navigation of thrombotic lesions in clinical applications.

TGF-β1 and TGFβR2 Gene Polymorphisms in Patients with Unstable Angina.

Acute coronary syndromes result from a sudden reduction in the lumen of a coronary artery as a result of atherosclerotic plaque rupture, its swelling or the formation of thrombotic lesions. Many mediators with inflammatory, prothrombotic and proatherogenic effects have been shown to be involved, including numerous cytokines, chemokines, adhesion molecules and growth factors. TGF-β1 is a pleiotropic cytokine found in various cells that regulates cell growth, differentiation and matrix production. The aim of our study was to assess the association between polymorphisms in the TGF-β1 gene (rs1800469, rs1800470) and polymorphisms in the TGFBR2 receptor gene (rs6785358, rs9838682) and the risk of unstable angina, as well as selected clinical parameters affecting the risk of ischemic heart disease. The study included 232 patients with unstable angina. The diagnosis of unstable angina was made by typical clinical presentation and confirmation of significant coronary artery lumen stenosis (&gt;70%) during coronary angiography. There were no statistically significant differences in the distribution of TGFBR2 rs6785358 and rs9838682 genotypes and haplotypes between patients with unstable angina and control subjects. We observed increased values of plasma total and LDL cholesterol levels, as well as triglycerides, in patients with the TGFBR2 rs9838682 AA genotype. In patients with the TGFBR2 rs6785358 AA genotype, we noted increased BMI values. There were no statistically significant associations between other studied polymorphisms and clinical parameters. Polymorphisms in the TGF-β1 gene (rs1800469, rs1800470) and polymorphisms in the TGFBR2 receptor gene (rs6785358, rs9838682) are not significant risk factors for unstable angina in our population. The TGFBR2 gene rs9838682 polymorphism may influence the lipid parameters in patients with coronary artery disease.

The impact of antiphospholipid antibodies in Takayasu arteritis.

The significance of antiphospholipid antibodies (aPL) is controversial in Takayasu arteritis (TA). This study was conducted to explore the frequency of aPL and their association with disease-related complications in TA. : This cross-sectional study was conducted to investigate the presence of anti-cardiolipin (aCL), anti-beta 2 glycoprotein- 1(aβ2G1) antibodies, and lupus anticoagulant (LA) in TA patients. TA patients admitted to the Department of Rheumatology of Hacettepe University Faculty of Medicine between December 2015 and September 2016 who fulfilled the American College of Rheumatology (ACR) classification criteria for TA were consecutively enrolled in the study. Patients were grouped according to aPL positivity and compared in terms of disease manifestations, type of vascular involvement at diagnosis, and vascular complications/interventions attributable to TA. Fifty-three TA (49 female) patients were enrolled in the study. We detected 9 (16.9%) patients with IgM and/or IgG aβ2G1 and/or LA positivity. There were no patients with positive aCL. All aβ2G1 titers were low. There were no differences in terms of symptoms, signs, type of vascular involvement, the number of patients with disease-related complications or vascular interventions/surgery between aPL (+) and aPL(-) groups (p > 0.05 for all). The number of patients with thrombotic lesions was similar between the groups (p > 0.05). There were no patients with a history of venous thrombosis or on anticoagulant treatment in the aPL(+) group. Only 1 patient with IgM aβ2G1 (+) had a history of pregnancy loss. Our results indicate that aPL positivity is not rare in TA. On the other hand, all aPL titers were low and no differences were found in the frequency of disease-related complications between aPL(+) and aPL(-) patient groups. Only TA patients with atypical manifestations with high suspicion of aPL-related complications should be considered to be investigated for aPL.

Association of High Mobility Group Box-Protein 1 and Platelet Microparticles in Patients After Hematopoietic Stem Cell Transplantation.

Thrombotic complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly impact transplant outcomes. We focused on high mobility group box-protein (HMGB)1, one causative agent of thrombotic lesions in allo-HSCT, and investigated its association with platelets. We statistically analyzed available data from 172 patients with hematopoietic malignancies receiving allo-HSCT. A significant enhancement of monocyte-chemotactant protein-1, HMGB1, and platelet-derived microparticle (PDMP) levels was observed at day 0 after transplantation as compared to pre-transplantation. Multivariate analysis of the association among HMGB1 and 16 factors on day 0 revealed a significant correlation of HMGB1 levels with thrombin-antithrombin complex, interleukin-6, and PDMPs. High mobility group box-protein 1-induced procoagulant platelet induction and PDMP generation were performed in vitro using healthy platelets. High mobility group box-protein 1-induced PDMP generation was suppressed by toll-like receptor inhibitors and recombinant thrombomodulin. These results suggest that HMGB1 contributes to platelet activation in patients after allo-HSCT and is associated with PDMP-related thrombotic complications.

The Occurrence of Thrombotic Complications Due to Combat Trauma Against the Background of the COVID-19 Pandemic

An important point in the provision of highly specialized cardiac surgical care for combat trauma is determination of the optimal time, method and volume of surgical intervention, taking into account the persisting threat of infection with the SARS-COV-2 virus and associated thrombotic complications.&#x0D; The aim. To investigate the mechanism of development and methods of prevention of thrombotic complications resulting from combat trauma against the background of the COVID-19 pandemic.&#x0D; Materials and methods. We analyzed clinical case of patient R., a 37-year-old soldier with a postinfarction thrombosed aneurysm of the left ventricle. The patient underwent standard clinical and laboratory tests, electrocardiography, echocardiography, coronary angiography, computed tomography of the chest, duplex scanning of carotid arteries, arteries and veins of the upper and lower extremities. It was established that 4 months ago, during a combat mission, the service-man received a mine-explosive injury, shrapnel wounds of lower extremities, multifragmentary fracture of the right ϐibula and a gunshot wound to the right chest. The causes of post-traumatic myocardial infarction are mine-explosive injury, intramural course of the left anterior descending artery, youngage, poorly developed collaterals of coronary arteries, long-term transportation during the stages of medical evacuation and post-traumatic stress disorder. A month ago, the patient was diagnosed with COVID-19, thromboembolism of the right main branch of the pulmonary artery, for which thrombolytic therapy was performed. Follow-up computed tomography showed the signs of thromboembolism of the pulmonary arteries. Ultrasound examination revealed thromboses of upper and lower limbs. Thrombotic complications against the background of combat polytrauma are the result of hypercoagulation, acute inϐlammation with the release of proinϐlammatory cytokines and damage of the endothelium. SARS-COV-2 infection triggers a state of hypercoagulation and creates additional conditions for the occurrence of arterial and venous thrombosis. Considering the nature of the thrombotic lesions, was made a decision to postpone the cardiosurgical intervention for 3 months.&#x0D; Conclusions. Thrombotic complications are an urgent problem after combat trauma. COVID-19 is an additional risk factor for hypercoagulation and a reason for delaying elective cardiac surgery. Conducting an electrocardiography to the wounded, regardless of age, is crucial for timely diagnosis andtreatment of acute coronary events. It is important to initiate anticoagulant therapy after eliminating all possible sources of bleeding due to the high risk of thrombotic complications against the background of chest trauma and limb fractures.

59 THE SHARK-FIN THAT EMERGES AND IMMERGES: A CASE REPORT OF TRANSIENT AND RIPETITIVE TRIANGULAR QRS-ST-T.

Abstract Introduction Shark fin sign, also known as triangular QRS-ST-T waveform (TW), is characterized by a giant R wave (amplitude ≥ 1 mV) resulting from the fusion of the QRS complex, the ST-segment and the T wave and showing triangular morphology. TW pattern is quite uncommon and reveals a life-threatening condition that needs aggressive management. Early recognition is important to prevent acute complications such as ventricular arrhythmias and cardiogenic shock. Case presentation A 45-years old black man with history of arterial hypertension presented with out-of-hospital cardiac arrest (OHCA) at his workplace. Extracorporeal cardiopulmonary resuscitation started immediately and return of spontaneous circulation occurred after 11 minutes and 2 DC shocks. Then he was transferred to our emergency department (ED). At arrival he was hemodynamically stable, ECG showed atrial fibrillation without any repolarization abnormalities and echocardiogram revealed left ventricular hypertrophy (IVS 12mm, PW 12mm) and normal biventricular function. Normal electrolytes and high-sensitivity troponin level of 14 (n.v. 0.01-19.8 ng/L) were found at the blood test. Sedation in the ED was needed due to psychomotor agitation. He was then transferred to the CCU where spontaneous cardioversion to sinus rhythm occurred, and no additional arrhythmias were noted at continuous ECG monitoring. After ten hours, while the patient was still under sedation, ECG monitoring revealed a progressive QRS-ST segment elevation in inferior leads up to a triangular QRS-ST-T giant waveform (“Shark fin sign”), without hemodynamic deterioration. After approximately 3 minutes the ECG showed a progressive and complete regression to a normal waveform. An emergent beside echocardiogram demonstrated inferior wall hypokinesia, but normal pump function. The episode repeated 5 more times in the following hour, waiting for cath lab personnel. Coronary angiography revealed a sub-occlusive mid RCA stenosis without any thrombotic lesion. Percutaneous coronary intervention (PCI) with the implantation of one drug eluting stent (DES) was performed. After the procedure the patient was hemodynamically and electrically stable. ECG did not show any other abnormality and no episodes of recurrent ST-elevation occurred. Sedation was suspended and no focal neurological deficits were noted. Discussion Shark fin sign is the expression of abrupt total deprivation of blood flow in large areas of myocardium that cause massive slowing of transmural electrical conduction. These electrical differences may be at the base of the triangular R waves and predispose to VF induction and cardiogenic shock. This sign is very rare, with an annual incidence of 0.7% in patients admitted for STEMI, and in most of the cases is described in the occlusion of the LAD. In our case we assisted to transient but repetitive inferior triangular ST-elevation with complete regression to normal ECG. The coronary angiogram showed non-obstructive lesion of the RCA. This phenomenon was probably the expression of RCA's plaque coronary vasospasm that caused the ECG shark fin sign and cardiac arrest. Conclusion Shark fin electrocardiographic waveform is an uncommon pattern of STEMI and may be the expression of thrombotic coronary occlusion as well as massive coronary vasospasm. This sign correlates with high risk of cardiogenic shock, electrical instability, and cardiac arrest, thus requiring prompt and aggressive management.

Nephrosclerosis in young patients with malignant hypertension.

Nephrosclerosis is one of the histopathological consequences of severe or malignant hypertension (MH), some of the pathophysiology of which has been extrapolated from essential polygenetic arterial hypertension. Despite our recent description of unsuspected ciliopathies with MH, causes of MH in young patients with severe renal impairment are poorly understood. To refine and better describe the MH phenotype, we studied clinical and prognostic factors in young patients receiving a kidney biopsy following their first episode of MH. Patients were identified retrospectively and prospectively from eight centres over a 35-year period (1985-2020). Keywords were used to retrospectively enrol patients irrespective of lesions found on renal biopsy. A total of 114 patients were included, 77 (67%) of whom were men, average age 34years, 35% Caucasian and 34% African origin. An isolated clinical diagnosis of severe nephrosclerosis was suggested in only 52% of cases, with 24% primary glomerulopathies. Only 7% of patients had normal renal function at diagnosis, 25% required emergency dialysis and 21% were eventually transplanted. Mortality was 1% at the last follow-up. Independent prognostic factors significantly associated with renal prognosis (6-month dialysis) and predictive of end-stage renal disease were serum creatinine on admission {odds ratio [OR] 1.56 [95% confidence interval (CI) 1.34-1.96], P<.001} and renal fibrosis >30% [OR 10.70 (95% CI 1.53-112.03), P=.03]. Astonishingly, the presence of any thrombotic microangiopathy lesion on renal biopsy was an independent, protective factor [OR 0.14 (95% CI 0.02-0.60), P=.01]. The histopathological hallmark of nephrosclerosis was found alone in only 52% of study patients, regardless of ethnicity. This suggests that kidney biopsy might be beneficial in young patients with MH.

Comparison of imaging findings on three-dimensional black-blood enhanced MR imaging between intracranial atherosclerotic occlusion and thrombotic occlusion

PurposeThe purpose of this study was to compare the imaging findings on three-dimensional (3D) black-blood (BB) contrast-enhanced MR imaging between intracranial atherosclerotic occlusion (IAO) and thrombotic occlusion (TO) of the middle cerebral artery (MCA) territory. Materials and methodsFrom August 2020 to September 2021, we retrospectively reviewed the BB contrast-enhanced MR imaging of patients visiting the emergency room for evaluation of acute ischemic stroke. In total, 77 patients with complete occlusion of the MCA territory on 3D BB contrast-enhanced MR imaging and cerebral angiography were enrolled in this study. We divided the IAO and TO groups according to occlusion causes based on angiography findings. ResultsOf 77 patients, 44 (57.1%) had an IAO in the M1 and M2 and 33 had a TO. Lesion length contrast enhancement (CE) in patients with a TO was significantly longer than that in patients with an IAO (18.95 mm [IQR: 20.91] vs. 7.1 mm [8.92], p <0.001). Overall, 38 (39.4%) patients showed a disconnection of CE on 3D BB contrast-enhanced MR imaging, and 35 showed CE before and after the stenotic or thrombotic lesion. Symptomatic lesions on diffusion-weighted imaging in the TO group were significantly higher than that of the IAO group (97.0% vs, 70.5%, p = 0.003). ConclusionThe long segment CE on 3D BB contrast-enhanced MR imaging was related to TO of MCA. CE before and after a stenotic or thrombotic lesion is a common finding on 3D BB contrast-enhanced MR imaging.

Abstract 15424: The Toxic Tango: Tyrosine Kinase Inhibitors (TKI) and Immune Checkpoint Inhibitors (ICI) Toxicities

Introduction: ICI and TKI have several cardiotoxicity side effects. We present a case of TKI-ICI toxicity resulting in multiorgan inflammatory syndrome with myocarditis and thrombotic STEMI that was treated with high-dose steroids and PCI. Case Presentation: 72-year-old man presented with acute SOB and inferior STEMI. He complains of severe DOE for the past 3 months, chronic diarrhea, and altered mental status. PMH of renal cell carcinoma (RCC) limited to kidney s/p nephrectomy. Follow-up CT scan with 4cm inferior left adrenal gland mass avid for FDG-PET and IR-biopsy positive for RCC. He was started on Pembrolizumab 200mg IV q3 weeks and axitinib 5mg PO q12h for the past 5 months. Investigation: LHC showed a thrombotic lesion in RCA with normal rest of coronaries without evidence of atherosclerosis or bystander plaque with successful PCI-DES. TTE with inferior wall hypokinesis and moderate pericardial effusion with organized material. Elevated CRP/ESR. Despite PCI, he is unable to walk 200ft due to DOE and needs supplemental O2. VQ scan low % for PE, PFT mild obstructive disease with severe reduction DLCO, and HRCT moderate emphysema, bronchial/ septal thickening, and normal hemodynamics in RHC. CMR demonstrated moderate pericardial effusion with internal debris, LVEF 38%, myocardial edema, and delayed gadolinium enhancement from base to apical inferior wall. Treatment: Empirical trial of IV-methylprednisolone 500mg IV q12 was started with drastic improvement of shortness of breath, resolution of AMS, ESR/CRP, and discontinuation of oxygen. Follow-up TTE with normal LVEF and resolution of pericardial effusion. Conclusions: ICI-Myocarditis is a severe irAE. The diagnosis requires clinical suspicion and exclusion of other cardiac conditions due to the high fatality rate. Early recognition and prompt treatment are needed to improve mortality. TKI-related arterial-thromboembolic events is not common but if present different therapy options should be offered.

SELL and GUCY1A1 Gene Polymorphisms in Patients with Unstable Angina.

Acute ischaemia is mostly caused by the rupture of an unstable atherosclerotic plaque in a coronary artery, resulting in platelet accumulation and thrombus formation, which closes the lumen of the coronary vessel. Many different factors can cause atherosclerotic plaques to occlude the lumen of a coronary artery, including factors that increase vascular inflammation and blood platelet aggregation, as well as genetic factors. L-selectin is an adhesion molecule encoded by the human SELL gene, playing an important role in leukocyte adhesion to the endothelium and the development of inflammation. Guanylate cyclase 1 soluble subunit alpha 1 (GUCY1A1) is a gene that affects vasoreactivity and platelet function, thereby influencing thrombotic processes and the risk of developing thrombotic lesions in the coronary vessels. In SELL and GUCY1A1 genes, several polymorphisms have been detected, which may affect gene expression. The aim of our study was to assess the association between the SELL rs2205849 and rs2229569 and GUCY1A1 rs7692387 polymorphisms with the risk of acute coronary syndromes in the form of unstable angina pectoris, and the association between these polymorphisms and selected clinical parameters affecting the risk of developing ischemic heart disease. The study included 232 patients with unstable angina. The diagnosis of unstable angina was achieved by a typical clinical presentation and confirmation of significant coronary artery lumen stenosis (>70%) during coronary angiography. There were no statistically significant differences in GUCY1A1 rs7692387 and SELL rs2205849 and rs2229569 polymorphism distribution between the total study and the control groups. However, when only analysing patients over 55 years of age, we found a decreased frequency of the GUCY1A1 rs7692387AA genotype (AA vs. GA + GG, OR: 0.07; 95% CI: 0.01–0.78) and an increased frequency of the SELL rs2205849 CC genotype (CC vs. TC + TT p = 0.022) and SELL rs2229569 AA genotype (AA vs. GA + GG p = 0.022) in patients with unstable angina. Our results suggest that the SELL rs2205849 and rs2229569 and GUCY1A1 rs7692387 polymorphisms are not risk factors for unstable angina in the Polish population. The GUCY1A1 rs7692387 polymorphism may increase the risk of unstable angina in patients younger than 55 years, while the SELL polymorphisms rs2205849 and rs2229569 may increase the risk of unstable angina in patients older than 55 years in the Polish population.

Prevalence and impact of TWILIGHT criteria in all-comer patients undergoing percutaneous coronary intervention

Abstract Background The Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention (TWILIGHT) randomized clinical trial demonstrated that in selected high risk patients who took ticagrelor and aspirin for 3 months after percutaneous coronary intervention (PCI), continuing ticagrelor alone was associated with significantly less bleeding events than ticagrelor plus aspirin and did not lead to ischemic harm over a period of 1 year (1). The prevalence and risk of adverse events of patients fulfilling the TWILIGHT inclusion criteria in real-world setting is unclear. Purpose To elucidate the prevalence and prognosis of patients fulfilling the TWILIGHT inclusion criteria. Methods Patients that received at least one drug eluting stent in a coronary artery at a large tertiary center (Mount Sinai Hospital, New York) were considered for inclusion. As in the TWILIGHT trial, individuals on chronic oral anticoagulation treatment, with STEMI, cardiogenic shock, on dialysis, with prior stroke, or platelet count &amp;lt;100,000 were excluded. Patients were stratified in two groups: 1) TWILIGHT-like patients, who met at least one clinical (age ≥65 years, female sex, established vascular disease, diabetes mellitus, estimated glomerular fraction rate &amp;lt;60mL/min, acute coronary syndrome with troponin increase) and one angiographic (multivessel coronary artery disease [CAD], stent length &amp;gt;30mm, thrombotic target lesion, bifurcation requiring 2 stents, left main or proximal left anterior descending artery lesion, atherectomy device use, SYNTAX score ≥23) TWILIGHT inclusion criterion; 2) Non-TWILIGHT-like patients, who did not fulfil at least one clinical and one angiographic TWILIGHT inclusion criterion. The primary outcome was a composite of death, myocardial infarction (MI), stroke. Secondary outcomes included bleeding, components of the primary outcome, target vessel and target lesion revascularization, stent thrombosis. All events were assessed at 1 year after PCI. Results Out of 30,470 patients undergoing PCI between 2012 and 2019, 13,236 were included in the current analysis. TWILIGHT criteria were met in 11,018 (83%) patients. Established vascular disease and multivessel CAD were the most frequently fulfilled criteria. At 1 year, TWILIGHT-like patients were at higher risk for the primary outcome (3.2% vs 1.1%, HR 2.85, 95% CI 1.83–4.44), severe bleeding (3.3% vs 1.8%, HR 1.86, 95% CI 1.32–2.62), all-cause death (1.4% vs 0.4%, HR 3.63, 95% CI 1.70–7.77), myocardial infarction (1.8% vs 0.6%, HR 2.81 95% CI 1.56–5.04), TVR (7.8% vs 4.1%, HR 1.94, 95% CI 1.53–2.47), TLR (5.1% vs 1.7%, HR 2.98 95% CI 2.07–4.29). Stent thrombosis and stroke rate were generally low and did not differ between patients meeting or not the TWILIGHT inclusion criteria. Conclusion Among all-comer patients undergoing PCI, the fulfillment of the TWILIGHT inclusion criteria is frequent and is associated with a higher risk of death, ischemic and bleeding complications Funding Acknowledgement Type of funding sources: None.

Contemporary approach to thrombus containing lesions during primary percutaneous coronary interventions in ST-segment elevation myocardial infarction (from the ORPKI National Registry in Poland)

Abstract Background In the era of potent P2Y12 inhibitors, according to current guidelines on ST-segment elevation myocardial infarction (STEMI), treatment with glycoprotein IIb/IIIa inhibitors (GPI) should be limited to selected bail-out or highly thrombotic situations. Similarly, aspiration thrombectomy (AT) is downgraded in current guidelines for very selective but not routine usage. Both recommendations make the treatment of thrombus containing lesions somewhat defensive, underlining the need for an individualized approach to STEMI patients. However, data concerning current clinical practice of such approach are limited. Purpose We examined the prevalence, procedural characteristics, and predictors of GPI administration and AT usage in all-comers contemporary STEMI patients referred to primary PCI in Poland. Methods We focused on 116,873 consecutive STEMI patients undergoing primary PCI in Poland between 2015 and 2020. Results GPIs were administered in 29.3% of patients and AT was used in 11.6%, with combined treatment with GPI and AT in 6.1% of patients. There was a slight trend towards a decrease in GPI and AT usage during the analyzed years. On the opposite, there was a rapid growth of the ticagrelor/prasugrel usage rate from 6.5% in 2015 to 48.1% in 2020 (Figure 1). Patients with periprocedural GPI administration and combined strategy with GPI and AT were younger, more often men, with history of smoking and presented with cardiogenic shock on admission. They were less likely to have diabetes, chronic kidney disease and previous stroke. Occluded infarct-related artery in baseline angiography and no-reflow during PCI were the strongest independent predictors of GPI administration and combined usage of GPI and AT in a multivariate logistic regression model. Similarly, administration of ticagrelor/prasugrel was an independent predictor of both adjunctive treatment strategies (see table for details). Conclusions Despite the rapid growth of potent P2Y12 inhibitors usage in Poland in recent years, GPI and AT are selectively used at a stable level during primary PCI in highly thrombotic STEMI lesions. Funding Acknowledgement Type of funding sources: None.

Venous stent patency is independent of total stented length in nonthrombotic iliac vein and post-thrombotic venous stenoses

ObjectiveVenous stenting has become the preferred treatment of symptomatic outflow obstruction due to nonthrombotic iliac vein lesions (NIVLs) and post-thrombotic venous stenoses (PTs). A paucity of data exists regarding the effect of stent length on patency rates after intervention. We evaluated the association between stent length and patency in patients treated for iliofemoral venous outflow obstruction. MethodsThe institutional review board approved the present study. A total of 161 patients had undergone venous stenting for NIVLs and thrombotic disease from January 2016 to April 2021. For thrombotic disease, patients with PTs and those with acute deep vein thrombosis (DVT) with underlying outflow obstruction were included. The patient characteristics evaluated included gender, age, body mass index, diagnosed thrombophilia, a history of venous thromboembolism, and CEAP (clinical, etiologic, anatomic, pathophysiologic) score. All the patients had undergone multiplanar venography and intravascular ultrasound during the index procedure. The intravascular ultrasound findings were used to determine the diameter and length of the implanted stents. The patients were placed into two groups, those with stented lengths ≤100 mm and those with stented lengths >100 mm. The primary end point was stent patency between the two groups using duplex ultrasound at 6 months. ResultsA total of 108 patients (58.3% female) had had 6-month duplex ultrasound scans available for review. Their mean age was 55.6 ± 17.2 years. The mean body mass index was 31.7 ± 6.9 kg/m2. Overall, the 6-month patency was 89.9%. Of the 108 patients, 56 (51.9%) had had a total stented length of ≤100 mm with a 6-month patency of 92.9%. The remaining 52 patients (48.1%) had had a total stented length >100 mm with a 6-month patency of 86.5%. The rate of patency did not differ significantly between the two groups (P = .222). Stent patency at 6 months for patients with NIVLs was 98% (40 of 41). Stent patency for patients with PTs was 84% (32 of 38). Patency for patients with acute DVT who had undergone stenting after thrombectomy was 86% (25 of 29). Overall, 10 patients with thrombotic disease, including PT and acute DVT, had developed stent thrombosis. The total stented length was not predictive of the loss of patency. ConclusionsThese findings suggest that the length of stent coverage does not confer an increased likelihood of stent thrombosis for patients with iliofemoral venous obstruction. Interventionalists should treat the affected venous segments identified on intravascular ultrasound and effectively stent from normal to normal venous areas, regardless of the stent length required. These results suggest that the total stented length is not a risk factor for stent thrombosis for both NIVL and thrombotic iliofemoral venous lesions.

Platelets in the NETworks interweaving inflammation and thrombosis.

Platelets are well characterized for their indispensable role in primary hemostasis to control hemorrhage. Research over the past years has provided a substantial body of evidence demonstrating that platelets also participate in host innate immunity. The surface expression of pattern recognition receptors, such as TLR2 and TLR4, provides platelets with the ability to sense bacterial products in their environment. Platelet α-granules contain microbicidal proteins, chemokines and growth factors, which upon release may directly engage pathogens and/or contribute to inflammatory signaling. Additionally, platelet interactions with neutrophils enhance neutrophil activation and are often crucial to induce a sufficient immune response. In particular, platelets can activate neutrophils to form neutrophil extracellular traps (NETs). This specific neutrophil effector function is characterized by neutrophils expelling chromatin fibres decorated with histones and antimicrobial proteins into the extracellular space where they serve to trap and kill pathogens. Until now, the mechanisms and signaling pathways between platelets and neutrophils inducing NET formation are still not fully characterized. NETs were also detected in thrombotic lesions in several disease backgrounds, pointing towards a role as an interface between neutrophils, platelets and thrombosis, also known as immunothrombosis. The negatively charged DNA within NETs provides a procoagulant surface, and in particular NET-derived proteins may directly activate platelets. In light of the current COVID-19 pandemic, the topic of immunothrombosis has become more relevant than ever, as a majority of COVID-19 patients display thrombi in the lung capillaries and other vascular beds. Furthermore, NETs can be found in the lung and other tissues and are associated with an increased mortality. Here, virus infiltration may lead to a cytokine storm that potently activates neutrophils and leads to massive neutrophil infiltration into the lung and NET formation. The resulting NETs presumably activate platelets and coagulation factors, further contributing to the subsequent emergence of microthrombi in pulmonary capillaries. In this review, we will discuss the interplay between platelets and NETs and the potential of this alliance to influence the course of inflammatory diseases. A better understanding of the underlying molecular mechanisms and the identification of treatment targets is of utmost importance to increase patients’ survival and improve the clinical outcome.

Intravascular ultrasound evaluation during iliofemoral venous stenting is associated with improved midterm patency outcomes

ObjectiveIntravascular ultrasound (IVUS) examination is increasingly used in the treatment of iliofemoral venous disease and provides more sensitive and specific detection of stenotic lesions when compared with traditional multiplanar venography alone. Correlations with deep venous stent patency, however, have not yet been investigated. The objective of the study was to evaluate the impact of the use of IVUS examination in addition to multiplanar venography on iliofemoral venous patency. MethodsConsecutive patients who underwent stenting for symptomatic thrombotic or nonthrombotic iliofemoral venous lesions (NIVLs) between 2014 and 2020 at a single institution were identified and divided into two groups based on whether IVUS examination was used before stent deployment in addition to multiplanar venography compared with venography alone. A retrospective review of demographic, operative, and follow-up data was performed. Thirty-day and 2-year stent patency were measured as primary end points. χ2 analysis, logistic regression models, and Kaplan-Meier survival analysis were used to determine outcomes. Technical details and outcomes were additionally examined among patients treated for acute deep venous thrombosis, post-thrombotic syndrome, or NIVLs separately on subgroup analysis. ResultsWe identified 150 patients (173 limbs, 23 bilateral) who underwent iliofemoral stenting during the study period at our institution (mean age: 48.8 ± 16.8 years, 61% female). Adjunctive IVUS utilization before stent deployment was reported in 69 of 173 (39.9%) treated limbs. IVUS examination was more likely to be used in patients who underwent stenting for NIVLs compared with thrombotic disease (41.0% vs 11.2%, P < .01). There was no difference in the number of stents deployed between IVUS and non-IVUS cohorts. However, IVUS examination was associated with the increased total length of the stent deployed (126 ± 56 vs 112 ± 48 mm, P = .04) and a higher rate of infrainguinal stent extension (17.4% vs 6.7%, P = .03). In addition, mean stent diameter was significantly higher when IVUS examination was performed before stent placement (16.3 ± 3.7 vs 15.2 ± 1.9 mm, P < .01). Both 30-day (98.5% vs 89.4%, P = .02) and 2-year (90.3% vs 78.7%, P = .03) primary patency were significantly higher in the IVUS cohort. Adjunctive IVUS use was found to significantly protect against stent reintervention at 2 years on adjusted Cox regression analysis (hazard ratio: 0.22, 95% confidence interval: 0.07-0.71, P = .01). ConclusionsAdjunctive IVUS utilization is associated with differences in stent diameter and length selections as well as landing segments in the treatment of thrombotic and nonthrombotic iliofemoral venous disease. IVUS examination before stent deployment significantly protects against 30-day and 2-year stent reintervention when compared with the use of multiplanar venography alone. These data provide stronger evidence for routine IVUS use in addition to venography before iliofemoral venous stenting.