The Effect of SGLT2 Inhibitor Therapy on Endothelial Progenitor Cell Function in Patients with Heart Failure.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to reduce the risk of cardiovascular mortality and hospitalizations in patients with heart failure (HF) with preserved or reduced ejection fraction (HFpEF or HFrEF). The mechanism for this benefit is not clear. Endothelial progenitor cells (EPCs) are bone-marrow derived cells able to differentiate into functional endothelial cells and participate in endothelial repair. The aim of the current study was to evaluate the effect of SGLT-2 inhibitors on the level and function of EPCs in patients with HF. We enrolled 20 patients with symptomatic HF, 12 with HFrEF and 8 with HFpEF (aged 73.3±10.2 years, 95% men). Blood samples were drawn at 2 time points: baseline and ≥3 months after initiation of SGLT-2 inhibitor therapy. Circulating EPC levels were evaluated by expression of VEGFR-2, CD34 and CD133 by flow-cytometry. EPCs colony forming units (CFUs) were quantified after 7 days in culture. The proportion of cells that co-expressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was higher following 3 months of SGLT-2 inhibitors [0.26% (IQR 0.10-0.33) vs. 0.55% (IQR 0.28-0.91), P=0.002; 0.12% (IQR 0.07-0.15) vs. 0.24% (IQR 0.15-0.39), P=0.001, respectively]. EPCs-CFU were also increased following SGLT-2 inhibitor treatment [23 (IQR 3.7-37.8) vs. 79.4 (IQR 25.1-110.25) colonies/106 cells, P=0.0039]. In patients with symptomatic HF, both HFpEF and HFrEF, treatment with SGLT-2 inhibitors is associated with an increase in circulating EPCs level and function. This augmentation in EPCs may be a contributing mechanism to the clinical benefit of SGLT-2 inhibitors in HF patients.

Percutaneous Coronary Interventions Using a Ridaforolimus-Eluting Stent in Patients at High Bleeding Risk.

BACKGROUND: Patients treated with percutaneous coronary intervention are often considered to be at a high bleeding risk (HBR). Drug-eluting stents have been shown to be superior to bare-metal stents in patients with HBR, even when patients were given abbreviated periods of dual antiplatelet therapy (DAPT). Short DAPT has not been evaluated with the EluNIR ridaforolimus-eluting stent. The aim of this study was to evaluate the safety and efficacy of a shortened period of DAPT following implantation of the ridaforolimus-eluting stent in patients with HBR. METHODS AND RESULTS: This was a prospective, multicenter, binational, single-arm, open-label trial. Patients were defined as HBR according to the LEADERS-FREE (Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug-Coated Stent versus the Gazelle Bare-Metal Stent in Patients at High Bleeding Risk) trial criteria. After percutaneous coronary intervention, DAPT was given for 1 month to patients presenting with stable angina. In patients presenting with an acute coronary syndrome, DAPT was given for 1 to 3 months, at the investigator's discretion. The primary end point was a composite of cardiac death, myocardial infarction, or stent thrombosis up to 1 year (Academic Research Consortium definite and probable). Three hundred fifteen patients undergoing percutaneous coronary intervention were enrolled, and 56.4% presented with acute coronary syndrome; 33.7% were receiving oral anticoagulation. At 1 year, the primary end point occurred in 15 patients (4.9%), meeting the prespecified performance goal of 14.1% (P<0.0001). Stent thrombosis (Academic Research Consortium definite and probable) occurred in 2 patients (0.6%). Bleeding Academic Research Consortium type 3 and 5 bleeding occurred in 6 patients (1.9%). CONCLUSIONS: We observed favorable results in patients with HBR who underwent percutaneous coronary intervention with a ridaforolimus-eluting stent and received shortened DAPT, including a low rate of ischemic events and low rate of stent thrombosis. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03877848.

Correlation between baseline immature platelets fraction levels and peak troponin in patients with acute myocardial infarction.

INTRODUCTION: Elevated peak cardiac troponin levels have been linked with increased morbidity and mortality in patients with acute myocardial infarction (AMI). Immature Platelets are young and relatively large platelets that are hyper-reactive and pro-thrombotic compared to regular platelets. Increased immature platelet fraction (IPF) has been associated with an elevated risk of thrombotic events. We hypothesize that patients with higher IPF levels during AMI, will experience a more severe infarct, leading to elevated peak troponin levels. METHODS: Clinical data from patients admitted to the cardiology division between 2018 and 2022, who were diagnosed with AMI and underwent an IPF testing. Univariate and multivariate regression analyses were performed to identify predictors of elevated peak troponin. RESULTS: Among the 277 patients diagnosed with AMI who underwent IPF testing, 113 had (STEMI) and 164 had (NSTEMI). The median value of IPF of 4.2% was used as the threshold for defining elevated IPF. Notably, among STEMI patients, those with IPF ≥ 4.2% had significantly higher peak troponin levels ( P  = 0.021). Conversely, no significant difference in peak troponin levels was observed among NSTEMI patients ( P  = 0.348). Multivariate analysis identified patients with STEMI in the higher IPF group as one of the significant predictors for elevated peak troponin levels. CONCLUSION: This study revealed a correlation between higher baseline IPF levels and increased peak troponin levels specifically in STEMI patients, while no such association was found in NSTEMI patients. Incorporating IPF levels above the median into risk stratification scores for STEMI patients may provide valuable support for adopting a more proactive therapeutic approach.

Performance of a novel artificial intelligence software developed to derive coronary fractional flow reserve values from diagnostic angiograms.

BACKGROUND: Although invasive measurement of fractional flow reserve (FFR) is recommended to guide revascularization, its routine use is underutilized. Recently, a novel non-invasive software that can instantaneously produce FFR values from the diagnostic angiograms, derived completely from artificial intelligence (AI) algorithms has been developed. We aim to assess the accuracy and diagnostic performance of AI-FFR in a real-world retrospective study. METHODS: Retrospective, three-center study comparing AI-FFR values with invasive pressure wire-derived FFR obtained in patients undergoing routine diagnostic angiography. The accuracy, sensitivity, and specificity of AI-FFR were analyzed. RESULTS: A total of 304 vessels from 297 patients were included. Mean invasive FFR was 0.86 vs. 0.85 AI-FFR (mean difference: -0.005, P  = 0.159). The diagnostic performance of AI-FFR demonstrated sensitivity of 91%, specificity 95%, positive predictive value 83% and negative predictive value 97%. Overall accuracy was 94% and the area under curve was 0.93 (95% CI 0.88-0.97). 105 lesions fell around the cutoff value (FFR = 0.75-0.85); in this sub-group, AI-FFR demonstrated sensitivity of 95%, and specificity 94%, with an AUC of 0.94 (95% CI 88.2-98.0). AI-FFR calculation time was 37.5 ±â€…7.4 s for each angiographic video. In 89% of cases, the software located the target lesion and in 11%, the operator manually marked the target lesion. CONCLUSION: AI-FFR calculated by an AI-based, angio-derived method, demonstrated excellent diagnostic performance against invasive FFR. AI-FFR calculation was fast with high reproducibility.

Differential platelet activation through an interaction with spike proteins of different SARS-CoV-2 variants.

COVID-19 disease is associated with an increased risk of thrombotic complications, which contribute to high short-term mortality. Patients with COVID-19 demonstrate enhanced platelet turnover and reactivity, which may have a role in the development of thrombotic events and disease severity. Evidence has suggested direct interaction between SARS-CoV-2 and platelets, resulting in platelets activation. Here, we compare the effect of various SARS-CoV-2 spike variants on platelet activation. Engineered lentiviral particles were pseudotyped with spike SARS-CoV-2 variants and incubated with Platelet Rich Plasma obtained from healthy individuals. The pseudotyped SARS-CoV-2 exhibiting the wild-type Wuhan-Hu spike protein stimulated platelets to increase expression of the surface CD62P and activated αIIbß3 markers by 3.5 ± 1.2 and 3.3 ± 0.7 fold, respectively (P = 0.004 and 0.003). The Delta variant induced much higher levels of platelet activation; CD62P expression was increased by 6.6 ± 2.2 fold and activated αIIbß3 expression was increased by 5.0 ± 1.5 fold (P = 0.005 and 0.026, respectively). The Omicron BA.1 and the Alpha variants induced the lowest level of activation; CD62P expression was increased by 1.7 ± 0.4 and 1.6 ± 0.9 fold, respectively (P = 0.003 and 0.008), and activated αIIbß3 expression by 1.8 ± 1.1 and 1.6 ± 0.8, respectively (P = 0.003 and 0.001). The Omicron BA.2 variant induced an increase of platelets activation comparable to the Wuhan-Hu (2.8 ± 1.2 and 2.1 ± 1.3 fold for CD62P and activated αIIbß3 markers, respectively). The results obtained for various COVID-19 variants are in correlation with the clinical severity and mortality reported for these variants.

Clinical Use of CathPCI Registry Risk Score and Its Validation to Predict Long-Term Mortality.

Risk models to estimate percutaneous coronary intervention (PCI) mortality have limited value in complex high-risk patients. However, it was improved by a recently developed bedside model to predict in-hospital mortality using data from the American College of Cardiology CathPCI Registry that included 706,263 patients. The median risk-standardized in-hospital mortality rate was 1.9%. In an attempt to validate this model in patients admitted because of acute coronary ischemia to predict in-hospital, 30-day, and 1-year mortality, we applied the proposed risk score to the study population of the Acute Coronary Syndrome Israeli Survey (ACSIS). This study was conducted for 2 months in 2018 and included all patients admitted to 25 coronary care units and cardiology departments in Israel. The ACSIS included 1,155 patients admitted because of acute myocardial infarction and who underwent PCI. In-hospital, 30-day, and 1-year mortality were 2.3%, 3.1%, and 6.2%, respectively. The CathPCI risk score yielded an area under the receiver operating characteristic curve of 0.96 (95% confidence interval [CI] 0.94 to 0.99) for in-hospital mortality; 0.96 (95% CI 0.94 to 0.98) for the 30-day mortality, and 0.88 (95% CI 0.83 to 0.93) for the 1-year mortality. The current model also included frail patients, and those with aortic stenosis, refractory shock, and after cardiac arrest. In conclusion, the CathPCI Registry risk score was validated using data from the ACSIS. Because the ACSIS population comprised patients with acute ischemia including those with high-risk features this model demonstrates a wider scope of application compared with previous ones. In addition, the model seems to be suitable to predict also the 30-day and 1-year mortality.

A novel robotic radiation shielding device for electrophysiologic procedures: A prospective study.

BACKGROUND: A robotic Radiaction Shielding System (RSS) was developed to provide a full-body protection to all medical personnel during fluoroscopy-guided procedures, by encapsulating the imaging beam and blocking scattered radiation. OBJECTIVES: We aimed to evaluate its efficacy in real-world electrophysiologic (EP) laboratory- both during ablations and cardiovascular implantable electronic devices (CIED) procedures. METHODS: A prospective controlled study comparing consecutive real-life EP procedures with and without RSS using highly sensitive sensors in different locations. RESULTS: Thirty-five ablations and 19 CIED procedures were done without RSS installed and 31 ablations and 24 CIED procedures (17 with usage levels ≥70%) were done with RSS. Overall, there was 95% average usage level for ablations and 88% for CIEDs. For all procedures with ≥70% usage level and for all sensors, the radiation with RSS was significantly lower than radiation without RSS. For ablations, there was 87% reduction in radiation with RSS (76%-97% for different sensors). For CIEDs, there was 83% reduction in radiation with RSS (59%-92%). RSS usage did not increase procedure time and radiation time. User feedback showed a high-level of integration in the clinical workflow and safety profile for all types of EP procedures. CONCLUSIONS: For both CIED and ablation procedures the radiation with RSS was significantly lower than without RSS. Higher usage level brings higher reduction rates. Thus, RSS may have an important role in full-body protection to all medical personnel from scattered radiation during EP and CIED procedures. Until more data is available, it is recommended to maintain existing standard shielding.

Coronary artery disease among patients admitted with atrial fibrillation and chest pain.

INTRODUCTION: Patients who present to the emergency department with chest pain during an episode of atrial fibrillation (AF) impose a clinical challenge regarding the source of pain - being coronary artery disease (CAD) or AF in origin. The aim of this study was to identify clinical, imaging or laboratory markers which can predict significant CAD among patients with an AF episode and chest pain. METHODS: We included 57 consecutive patients admitted to our hospital with AF and chest pain. All patients underwent coronary evaluation. Significant CAD was defined as >50% stenosis in a major coronary artery by coronary angiography or cardiac CT. We compared CAD and non-CAD groups and analyzed risk factorsby regression analysis. RESULTS: Twenty-four patients (42%) were diagnosed with- and 33 patients (58%) without obstructive CAD. In a multivariate analysis of regional wall motion abnormality (RWMA), elevated troponin and hypertension were found to be predictors for CAD [odds ratio (OR), 22.4 (confidence interval (CI), 1.8-272.4; P = 0.02); OR, 5.6 (CI, 1-31.0; P = 0.05) and OR, 21.4 (CI, 1.6-284.6; P = 0.02), respectively]. There were no significant differences regarding the rate of typical chest pain at presentation in the CAD vs. the non-CAD group [13 (54%) vs. 20 (60%), P = 0.374], or in ECG ST-changes [12 (50%) vs.9 (27%), respectively; P = 0.08]. CONCLUSION: In patients who present acutely with chest pain and AF, troponin elevation and RWMA appear to be highly predictive of obstructive CAD, whereas clinical symptoms and ECG changes are not predictive. These findings may be helpful for guiding the management of patients admitted with AF and chest pain.

External applicability of the Effect of ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) trial: An analysis of patients with diabetes and coronary artery disease in the REduction of Atherothrombosis for Continued Health (REACH) registry.

AIMS: THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry. METHODS AND RESULTS: The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a 'THEMIS-eligible population' of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy. CONCLUSIONS: In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be 'THEMIS eligible.' CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov identifier: NCT01991795.

Inflammatory cytokines differ between patients with high versus low CHA2DS2-VASc scores in sinus rhythm-a possible mechanism for adverse cardiovascular events.

Background: The CHA2DS2-VASc score was shown to predict systemic thromboembolism and mortality in certain groups of patients in sinus rhythm (SR). Previous data showed that patients in SR with high CHA2DS2-VASc score have higher plasma levels of inflammatory markers such as sP-selectin and C-reactive protein. We further investigated this group. Methods: Blood samples were collected from consecutive patients in SR. Plasma was extracted and stored at -80 °C. Concentrations of a panel of soluble markers IL-1ß, IL-6, IL-8, IL-10, TNF-α and VEGF were measured by Magnetic Luminex Performance Assay. The PLF4 cytokine blood level was measured by ELISA. Results: 66 patients were enrolled (age 53 ± 18 years, 60% women). Patients with high CHA2DS2-VASc scores (n = 23) had significantly higher median IQR concentrations of TNF-α [10.34 (8.55,14.92) vs. 7.69 (6.06, 9.85) pg/ml, p = 0.009] and a trend towards higher levels of IL-1ß [0.59 (0.4,0.8) vs. 0.44 (0.31, 0.62) pg/ml, p = 0.07] and IL-8 [5.92 (4.5,9.4) vs. 5.04 (3.63, 6.04) pg/ml, p = 0.07], compared to the group with low scores (n = 43). Median IQR concentrations of VEGF, IL-6, IL-10 and PF4 did not significantly differ between the CHA2DS2-VASc score groups. Conclusion: Patients in SR with high versus low CHA2DS2-VASc scores have high plasma concentrations of systemic inflammation cytokines. The already proven high levels of sP-selectin, that promotes release of inflammatory cytokines from leukocytes, is in line with these results. This pro-inflammatory state in patients with high CHA2DS2-VASc scores, may explain the higher rate of adverse cardiovascular events associated with elevated CHA2DS2-VASc score even without atrial fibrillation.

Identification of protective biologic factors in patients with high cardiovascular risk, but normal coronary arteries (NormCorn).

BACKGROUND: Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. Telomere length has been shown to be correlated with genome stability and overall cell health. We hypothesized that both EPCs and telomere size are related to protective mechanisms against coronary artery disease. Our aim was to evaluate the level and function of circulating EPCs and telomere length in patients with multiple cardiovascular risk factors and anatomically normal coronary arteries vs. matched controls. METHODS: We included 24 patients, with coronary CTA demonstrating normal coronaries and a high risk of CAD of >10% by ASCVD risk estimator. Control groups included 17 patients with similar cardiovascular profiles but with established CAD and a group of 20 healthy volunteers. Circulating EPCs levels were assessed by flow cytometry for expression of vascular endothelial growth factor receptor 2, CD34 and CD133. The capacity of the cells to form colony forming units (CFUs) was quantified after 1 week of culture. Telomere length was determined by the southern blotting technique. RESULTS: Patients with high risk for CVD and normal coronaries had augmented EPCs function, compared with the CAD group (1.1 vs. 0.22 CFU/f; P = 0.04) and longer telomeres compared with the CAD group (10.7 kb vs. 2.8 kb P = 0.015). These patients displayed a similar profile to the healthy group. CONCLUSION: Patients with a high risk for CAD, but normal coronary arteries have EPCs function and telomere length which resemble healthy volunteers, and augmented compared with patients with established CAD, which could serve as a protective mechanism against atherosclerosis development in these high-risk patients.

Simultaneous Noninvasive Detection and Therapy of Atherosclerosis Using HDL Coated Gold Nanorods.

Cardiovascular disease (CVD) is a major cause of death and disability worldwide. A real need exists in the development of new, improved therapeutic methods for treating CVD, while major advances in nanotechnology have opened new avenues in this field. In this paper, we report the use of gold nanoparticles (GNPs) coated with high-density lipoprotein (HDL) (GNP-HDL) for the simultaneous detection and therapy of unstable plaques. Based on the well-known HDL cardiovascular protection, by promoting the reverse cholesterol transport (RCT), injured rat carotids, as a model for unstable plaques, were injected with the GNP-HDL. Noninvasive detection of the plaques 24 h post the GNP injection was enabled using the diffusion reflection (DR) method, indicating that the GNP-HDL particles had accumulated in the injured site. Pathology and noninvasive CT measurements proved the recovery of the injured artery treated with the GNP-HDL. The DR of the GNP-HDL presented a simple and highly sensitive method at a low cost, resulting in simultaneous specific unstable plaque diagnosis and recovery.

Comparison of Factors Associated with Inflammation, Thrombosis, and Platelet Reactivity as well as Turnover between Patients with High versus Low CHA2DS2-VASc without Atrial Fibrillation.

BACKGROUND: The CHA2DS2-VASc score has been shown to predict systemic thromboembolism and mortality in certain groups in sinus rhythm (SR), similar to its predictive value with atrial fibrillation (AF). OBJECTIVES: To compare factors of inflammation, thrombosis, platelet reactivity, and turnover in patients with high versus low CHA2DS2-VASc score in SR. METHODS: We enrolled consecutive patients in SR and no history of AF. Blood samples were collected for neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), immature platelet fraction (IPF%) and count (IPC), CD40 ligand, soluble P-selectin (sP-selectin) and E-selectin. IPF was measured by autoanalyzer and the other factors by ELISA. RESULTS: The study comprised 108 patients (age 58 ± 18 years, 63 women (58%), 28 (26%) with diabetes), In addition, 52 had high CHA2DS2-VASc score (³ 2 for male and ³ 3 for female) and 56 had low score. Patients with low scores were younger, with fewer co-morbidities, and smaller left atrial size. sP-selectin was higher in the high CHA2DS2-VASc group (45, interquartile ratio [IQR] 36-49) vs. 37 (IQR 28-46) ng/ml, P = 0.041]. Inflammatory markers were also elevated, CRP 3.1 mg/L (IQR 1.7-9.3) vs. 1.6 (IQR 0.78-5.4), P < 0.001; NLR 2.7 (IQR 2.1-3.8) vs. 2.1 (IQR 1.6-2.5), P = 0.001, respectively. There was no difference in E-selectin, CD40 ligand, IPC, or IPF% between the groups. CONCLUSIONS: Patients in SR with high CHA2DS2-VASc score have higher inflammatory markers and sP-selectin. These findings may explain the higher rate of adverse cardiovascular events associated with elevated CHA2DS2-VASc score.

Intravascular leiomyomatosis with cardiac extension: a case report.

BACKGROUND: Intravascular leiomyomatosis (IVL) with intracardiac extension is a rare benign tumour seen exclusively in women, characterized by proliferation of uterine smooth muscle cells through the venous circulation into the inferior vena cava (IVC) and the right heart chambers. CASE SUMMARY: A 47 years old women with history of previous hysterectomy due to myomatosis, presented with nausea, anorexia, and bilateral lower limb swelling over the preceding 2 months. An outpatient abdominal ultrasound discovered a mass in the IVC. Echocardiogram and computed tomography demonstrated a large intravascular mass extending from the pelvis to the right heart chambers. The tumour was completely removed in a concomitant open-heart surgery and laparotomy. Post-operative course was uncomplicated. A month later, the patient was feeling well and in good clinical condition. The histological analysis consisted with IVL. DISCUSSION: Intracardiac leiomyomatosis is a rare clinical condition which requires high index of suspicion. Multimodality imaging is usually required to establish the preoperative diagnosis, although the final diagnosis is achieved with tissue investigation. Complete surgical resection of the tumour is curative and associated with good long-term prognosis.

[COMPLETE ATRIOVENTRICULAR BLOCK DUE TO PULMONARY EMBOLISM].

INTRODUCTION: Pulmonary embolism, a common and potentially fatal clinical condition, occurs when a blood thrombus becomes lodged in the pulmonary vasculature and creates an acute increment in the pulmonary vascular resistance, which, in turn, creates a right ventricular strain. Among the more familiar electrocardiographic manifestations in acute pulmonary embolism is sinus tachycardia, right bundle branch block and ST-T abnormalities in the right precordium leads. Complete heart block or any type of bradycardia is uncommon. In our case report we present an 81 years old woman who was admitted to our institution with acute pulmonary embolism and complete atrioventricular block, which later resolved with appropriate anticoagulation therapy.

The Effect of Proprotein Convertase Subtilisin Kexin Type 9 Inhibitors on Circulating Endothelial Progenitor Cells in Patients with Cardiovascular Disease.

PURPOSE: Circulating endothelial progenitor cells (cEPCs) are vital to vascular repair by re-endothelialization. We aimed to explore the effect of proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) on cEPCs hypothesizing a possible pleiotropic effect. METHODS: Patients with cardiovascular disease (CVD) were sampled for cEPCs at baseline and following the initiation of PCSK9i. cEPCs were assessed using flow cytometry by the expression of CD34(+)/CD133(+) and vascular endothelial growth factor receptor (VEGFR)-2(+), and by the formation of colony-forming units (CFUs) and production of VEGF. RESULTS: Our cohort included 26 patients (median age 68 (IQR 63, 73) years; 69% male). Following 3 months of treatment with PCSK9i and a decline in low-density lipoprotein cholesterol levels (153 (IQR 116, 176) to 56 (IQR 28, 72) mg/dl), p < 0.001), there was an increase in CD34(+)/CD133(+) and VEGFR-2(+) cell levels (0.98% (IQR 0.37, 1.55) to 1.43% (IQR 0.90, 4.51), p = 0.002 and 0.66% (IQR 0.22, 0.99) to 1.53% (IQR 0.73, 2.70), p = 0.05, respectively). Functionally, increase in EPCs-CFUs was microscopically evident following treatment with PCSK9i (1 CFUs (IQR 0.0, 1.0) to 2.5 (IQR 1.5, 3), p < 0.001) with a concomitant increase in EPC's viability as demonstrated by an MTT assay (0.15 (IQR 0.11, 0.19) to 0.21 (IQR 0.18, 0.23), p < 0.001). VEGF levels increased following PCSK9i treatment (57 (IQR 18, 24) to 105 (IQR 43, 245), p = 0.006). CONCLUSIONS: Patients with CVD treated with PCSK9i demonstrate higher levels of active cEPCs, reflecting the promotion of endothelial repair. These findings may represent a novel mechanism of action of PCSK9i.

Effects of electret coating technology on coronary stent thrombogenicity.

Stent thrombosis (ST) is a catastrophic event and efforts to reduce its incidence by altering blood-stent interactions are longstanding. A new electret coating technology that produces long-lasting negative charge on stent surface could make them intrinsically resistant to thrombosis. We assessed the thrombogenicity of stents using an annular perfusion model with confocal microscopy, and determined the efficacy of electret coating technology to confer thrombo-resistant properties to standard stents. Using an annular perfusion chamber, Bare Metal Stent (BMS), standard uncoated DES (DES), and Electret-coated DES (e-DES) were exposed to human blood under arterial flow conditions. Deposits of fibrinogen and platelets on the stent surface were analyzed using immunofluorescence staining and confocal microscopy. Surface coverage by fibrinogen and platelets and the deposit/aggregate size were quantified using computerized morphometric analysis. The experimental methodology produced consistent, quantifiable results. Area of stent surface covered by fibrinogen and platelets and the average size of the deposits/aggregates were lowest for e-DES and highest on BMS, with DES in the middle. The size of fibrinogen-deposits showed no differences between the stents. The testing methodology used in our study successfully demonstrated that electret coating confers significant antithrombotic property to DES stents. These findings warrant confirmation in a larger study.

The Association between Multi-Vessel Coronary Artery Disease and High On-Aspirin Platelet Reactivity.

BACKGROUND: Multi-vessel coronary artery disease (MV-CAD) is correlated with worse clinical outcomes compared with single-vessel CAD (SV-CAD). The aim of this study was to evaluate the association between MV-CAD and high on-aspirin platelet reactivity (HAPR) in patients with stable CAD treated with aspirin. METHODS: The current study is an analysis of prospectively enrolled randomly selected patients with known stable CAD, who were taking aspirin (75-100 mg qd) regularly for at least one month, and had undergone coronary angiography at least 3 months prior to the enrollment to the study. EXCLUSION CRITERIA: acute coronary syndrome at the time of platelet function testing, active malignancy, acute infection, active inflammatory/rheumatic disease, major surgery in the past 6 months, chronic liver failure, treatment with oral anticoagulation, non-adherence with Aspirin and thrombocytopenia (<100 K/micl). Blood was drawn from the participants and sent for platelet function testing (VerifyNow, Instrumentation Laboratory Company, Bedford, Massachusetts, United States). MV-CAD was defined as >50% stenosis in ≥2 separate major coronary territories per coronary angiography. HAPR was defined as aspirin reaction units (ARU) >550. RESULTS: Overall, 507 patients were analyzed; age 66.7 ± 11.2, 17.9% women, 223 (44%) had MV-CAD. The rate of HAPR was significantly higher among patients with MV-CAD vs. SV-CAD (14.8% vs. 3.5%, p < 0.001, respectively). Furthermore, a "dose response"-like association was found between the number of stenotic coronary arteries and the rate of HAPR (3.5%, 13.5 and 17.3% for SV-CAD, 2-vessel and 3-vessel disease, respectively). In a multivariate analysis adjusted for potential confounders, MV-CAD was found to be a strong independent predictor of HAPR [OR = 1.8 (95%CI: 1.05-4.7), p = 0.014]. CONCLUSIONS: A significant association between MV-CAD and HAPR was found. Additional studies designed to investigate the mechanisms of HAPR and different therapeutic options for this subset of patients are warranted.