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

ABSTRACT: 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 this 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 vascular endothelial growth factor receptor-2 (VEGFR-2), CD34, and CD133 by flow cytometry. EPC colony forming units (CFUs) were quantified after 7 days in culture. The proportion of cells that coexpressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was higher following 3 months of SGLT-2 inhibitors [0.26% (interquartile range, IQR 0.10-0.33) versus 0.55% (IQR 0.28-0.91), P = 0.002; 0.12% (IQR 0.07-0.15) versus 0.24% (IQR 0.15-0.39), P = 0.001, respectively]. EPC CFUs were also increased following SGLT-2 inhibitor treatment [23 (IQR 3.7-37.8) versus 79.4 (IQR 25.1-110.25) colonies/10 6 cells, P = 0.0039]. In patients with symptomatic HF, both HFpEF and HFrEF, treatment with SGLT-2 inhibitors is associated with an increase in the level and function of circulating EPCs. This augmentation in EPCs may be a contributing mechanism to the clinical benefit of SGLT-2 inhibitors in patients with HF.

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.

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.

Impact of Calcium Channel Blockers on Aspirin Reactivity in Patients with Coronary Artery Disease.

PURPOSE: Calcium channel blockers (CCBs) do not reduce the risk of initial or recurrent myocardial infarction (MI) in patients diagnosed with stable coronary artery disease (CAD). The aim of this current study was to evaluate the association between CCBs and aspirin resistance in patients with CAD. METHODS: Patients with stable CAD who were regularly taking aspirin (75-100 mg qd) for at least 1 month prior to enrollment in the study were included. The VerifyNow system was used for platelet function testing with high on-aspirin platelet reactivity (HAPR) defined as aspirin reaction units (ARU) >550. We compared patients treated with CCBs versus control group. RESULTS: Five hundred three patients with CAD were included in this study, and 88 were treated with CCBs. Mean age (67.9±9.7 in the CCB group vs. 66.5±11.4 in the control group), gender (77.3 male vs. 82.9%), rates of diabetes mellitus (34.7 vs. 36.9%), rates of CKD (23.5 vs. 23.5%), dyslipidemia (85.1 vs. 85.3%), and statin therapy (89.5 vs. 90.7%) were similar. The mean ARU was 465.4±70.0 for patients treated with CCBs versus 445.2±60.0 in controls (p=0.006). Similarly, 15.9% of CCB patients demonstrated HAPR compared to 7.0% (p=0.006). The administration of CCBs was independently associated with HAPR in a multivariate analysis (OR 1.72, 95% CI: 1.04-8.91, p=0.047) as well as in propensity score matched analysis (OR 1.56; CI: 1.22-1.93; p<0.001). CONCLUSIONS: Usage of CCBs is positively correlated with aspirin resistance. These findings may suggest an adverse pharmacologic effect of CCBs among patients with stable CAD treated with aspirin.

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.

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.

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.

[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.

Thrombin Generation in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The optimal antithrombotic treatment for patients with atrial fibrillation (AF) that undergo percutaneous coronary intervention (PCI) is controversial. Dual therapy (clopidogrel and a direct oral anticoagulant [DOAC]) is safer than triple therapy (warfarin, aspirin, and clopidogrel), while efficacy is unclear. We aimed to evaluate thrombin generation (TG) under dual and triple therapy. METHODS: A noninterventional prospective trial in patients with AF undergoing PCI. Patients received 4 weeks of triple therapy with aspirin, clopidogrel, and a DOAC followed by aspirin withdrawal. TG was measured in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) at 3 five to 21 points, day 1 after PCI (TIME 0), 4 weeks after PCI (TIME 1), and 2 weeks after aspirin withdrawal (TIME 2). RESULTS: Twenty-three patients (18 men, median age 78 years, 83% with acute coronary syndrome) were included. Endogenous thrombin potential (ETP) in PPP was high at TIME 0 compared with TIME 1 (ETP 3,178 ± 248 nM vs. 2,378 ± 222 nM, p = 0.005). These results remained consistent when measured in PRP. No significant difference in ETP was found before (TIME 1) and after aspirin withdrawal (TIME 2) although few patients had high ETP levels after stopping aspirin. CONCLUSIONS: TG potential is high immediately after PCI and decreases 4 weeks after PCI in patients receiving triple therapy. TG remains constant after aspirin withdrawal in most patients, suggesting that after 1 month the antithrombotic effect of dual therapy may be similar to triple therapy.

Immature platelets in patients with Covid-19: association with disease severity.

Coronavirus disease 2019 (Covid-19) is associated with a high incidence of venous and arterial thromboembolic events. Currently, there are no clinical or laboratory markers that predict thrombotic risk. Circulating immature platelets are hyper-reactive platelets, which are associated with arterial thrombotic events. The aim of this study was to assess whether the proportion of circulating immature platelets is associated with disease severity in Covid-19 patients. Patients admitted with Covid-19 disease were prospectively assessed. Immature platelet count (IPC) and immature platelet fraction (IPF) were measured at admission and at additional time points during the hospital course using the Sysmex XN-3000 auto-analyzer. A total of 136 consecutive patients with Covid-19 were recruited [mean age 60 ± 19 years, 49% woman, 56 (41%) had mild-moderate disease and 80 (59%) had severe disease at presentation]. The median IPF% was higher in patients with severe compared to mild-moderate disease [5.8 (3.9-8.7) vs. 4.2 (2.73-6.45), respectively, p = 0.01]. The maximal IPC value was also higher in patients with severe disease [15 (10.03-21.56), vs 10.9 (IQR 6.79-15.62), respectively, p = 0.001]. Increased IPC was associated with increased length of hospital stay. Patients with severe Covid-19 have higher levels of IPF than patients with mild-moderate disease. IPF may serve as a prognostic marker for disease severity in Covid-19 patients.

Immature platelets in patients hospitalized with Covid-19.

Coronavirus disease 2019 (Covid-19) is associated with high incidence of venous and arterial thromboembolic events. Currently, there are no markers to guide antithrombotic therapy in Covid-19. Immature platelets represent a population of hyper-reactive platelets associated with arterial events. This prospective study compared consecutive Covid-19 patients (n = 47, median age = 56 years) to patients with acute myocardial infarction (AMI, n = 100, median age = 59 years) and a group of stable patients with cardiovascular risk factors (n = 64, median age = 68 years). Immature platelet fraction (IPF) and immature platelet count (IPC) were determined by the Sysmex XN-3000 auto-analyzer on admission and at subsequent time-points. IPF% on admission was higher in Covid-19 than the stable group and similar to the AMI group (4.8% [IQR 3.4-6.9], 3.5% [2.7-5.1], 4.55% [3.0-6.75], respectively, p = 0.0053). IPC on admission was also higher in Covid-19 than the stable group and similar to the AMI group (10.8 × 109/L [8.3-18.1], 7.35 × 109/L [5.3-10.5], 10.7 × 109/L [7.7-16.8], respectively, P < 0.0001). The maximal IPF% among the Covid-19 group was higher than the stable group and similar to the AMI group. The maximal IPC in Covid-19 was higher than the maximal IPC in both the stable and AMI groups (COVID-19: 14.4 × 109/L [9.4-20.9], AMI: 10.9 × 109/L [7.6-15.2], P = 0.0035, Stable: 7.55 × 109/L [5.55-10.5], P < 0.0001). Patients with Covid-19 have increased immature platelets indices compared to stable patients with cardiovascular risk factors, and as the disease progresses also compared to AMI patients. The enhanced platelet turnover and reactivity may have a role in the development of thrombotic events in Covid-19 patients.

Temporal trends in prognosis of patients with acute coronary syndrome complicated by ventricular tachyarrhythmia.

OBJECTIVES: To evaluate clinical characteristics and prognosis of patients presented with acute coronary syndrome (ACS) that developed ventricular tachyarrhythmia VTA and to analyse it according to the period of presentation. BACKGROUND: VTA is an infrequent yet serious complication of ACS. There is limited data regarding the incidence and prognostic implications of VTA in the last decade as compared with the previous decade. METHODS: We evaluated clinical characteristics, major adverse cardiovascular events, short and long- term mortality of patients hospitalised with ACS who were enrolled in the Acute Coronary Syndrome Israeli Survey (ACSIS) during the years 2000-2016. Patients were classified into three groups: no VTA, early VTA (≤48 hours of onset) and late VTA (>48 hours of onset). Data were analysed according to the period of presentation: early vs late period (years 2000-2006 and 2008-2016 accordingly). RESULTS: The study population comprised 15,200 patients. VTA occurred in 487 (3.2%) patients. Early VTA presented in 373/487 (77%) patients and late VTA in 114/487 (23%) patients. VTA's, occurring in ACS patients were associated with increased risk of in-hospital, 30-days, 1-year and 5-year mortality rates during both early and late periods compared with no VTA. Moreover, late VTA was associated with the highest mortality rate with up to 65% in 5-year follow up (P < .001). Nevertheless, late VTA was associated with a lower mortality rate in the late period compared with the early period. CONCLUSIONS: Any VTA following ACS was associated with high short- and long-term mortality rate. However, over the late period, there has been a significant improvement in survival rates, especially in patients with late VTA. This may be attributed to early and invasive reperfusion therapy, implantable cardioverter-defibrillator implantation and better medical treatment.

Circulating Endothelial Progenitor Cells in Patients with Heart Failure with Preserved versus Reduced Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a common clinical entity, with a mechanism that appears to involve endothelial dysfunction of the cardiac microcirculation. Endothelial progenitor cells (EPC) are bone marrow derived cells that are able to differentiate into functional endothelial cells and participate in endothelial surface repair. OBJECTIVES: To compare the level and function of EPCs in patients with HFpEF compared with heart failure with reduced ejection fraction (HFrEF) and control subjects. METHODS: We enrolled 21 patients with HFpEF (LVEF ≥ 50%, age 74.5 ± 9.9 years, 43% men, 48% diabetes), 20 patients with HFrEF (LVEF < 40%, age 70 ± 11.5 years, 90% men, 60% diabetes), and 11 control subjects with cardiovascular risk factors (age 53.3 ± 6.1years, 90% men, 64% diabetes). Circulating EPC levels were evaluated by expression of vascular endothelial growth factor receptor-2 (VEGFR-2), CD34, and CD133 by flow-cytometry. EPCs colony forming units (CFUs) were quantified after 7 days in culture. RESULTS: The proportion of cells that co-expressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was similar among the HFpEF and HFrEF groups, and significantly lower than in the control group. The number of EPC-CFUs was also similar among the two heart failure groups and significantly lower than the control group. CONCLUSIONS: Patients with HFpEF, like HFrEF, have significant reduction in EPC level and function.

Prognostic significance of reticulated platelet levels in diabetic patients with stable coronary artery disease.

Levels of reticulated platelets (RP) increase during high platelet turnover conditions, and have been shown to correlate with diabetes mellitus (DM) status. Little is known regarding the prognostic significance of levels of RP among patients with stable coronary artery disease (SCAD). The study consisted of patients with SCAD and DM, who visited our cardiology outpatient clinic between June 2016 and February 2017. RP levels were measured at baseline as immature platelet fraction (IPF)%, using flow cytometry. Outcomes at 2 years consisted of bleeding events and major adverse cardiovascular events (MACE), which included death, myocardial infarction, cerebrovascular accident and urgent revascularization. The study included 104 patients (mean age - 71.2 ± 9.5 years, 76.9% were male, and 83.7% had hypertension). IPF was significantly higher at baseline among patients who had suffered from a MACE (4.57% vs. 2.53%, p < .001), and lower in patients who had suffered from bleeding events, compared with those who had not (1.57% vs. 3.00%, p = .004). There were higher rates of MACE at higher IPF quartiles (p < .001, AUC-0.770), and higher rates of bleeding at the lowest quartiles (p = .007, AUC-0.781). In SCAD patients with DM, levels of RP are associated with a higher risk of MACE, and inversely correlated with the risk of bleeding.

Temporal trends in percutaneous coronary interventions thru the drug eluting stent era: Insights from 18,641 procedures performed over 12-year period.

BACKGROUND: The last decade, regarded as the DES era in PCI, has witnessed significant advances in the management of coronary disease. We aimed to assess temporal trends in the practice and outcome of percutaneous coronary intervention (PCI) during the drug eluting stent (DES) era. METHODS: We analyzed 18,641 consecutive PCI's performed between January 2004 and December 2016, distinguished by procedural date (Q1 : 2004-2006, n = 4,865; Q2 : 2007-2009, n = 4,977; Q3 : 2010-2012, n = 4,230; Q4 : 2013-2016, n = 4,569). RESULTS: At presentation, mean patients age was 65 (±11) years and 22.8% were females. Over time, there was a rise in the relative number of octogenarians (Q1 : 10.7% vs Q4 : 15.5%, P < 0.001) and an increase in the burden of most comorbidities (e.g., left ventricular dysfunction ≥ moderate and chronic kidney disease, P < 0.001 for both). Despite a 2-fold increase in the rate of complex interventions, and a 3-fold increase in the rate of unprotected left-main angioplasty (P < 0.001 for both), the radial approach was increasingly adopted (Q1 : 2% to Q4 : 63.5%, P < 0.001). DES implantation increased from 43% to 83% at the expense of bare metal stent (BMS) application, and accompanied by drug coated balloon sprout to 1.8%, P < 0.001. Kaplan-Meier survival curves revealed a time-based enhanced outcome, with a decreased rate of death, MI, target vessel revascularization and CABG over the years. CONCLUSIONS: In the last decade, PCI has evolved to offer better outcome to more elderly, sicker patient population, with more complex coronary disease interventions. The shift to second generation DES and to enhanced PCI techniques may explain part of this progress.

The effect of cessation of 2nd generation P2Y12 inhibitor therapy on platelet reactivity in patients 1 year after acute myocardial infarction.

To assess the effect of cessation of dual antiplatelet therapy (DAPT) regimens containing 2nd generation P2Y12 inhibitors on platelet reactivity, in patients who completed 12 months of DAPT following an acute myocardial infarction. Clinical data has shown an increased cardiovascular risk in the 90 days following cessation of DAPT. One possible explanation is a transient platelet hyper-reactivity after cessation of treatment. Data from patients treated with 2nd generation P2Y12 inhibitors is scarce. Patients who completed 12 month DAPT with prasugrel/ticagrelor underwent serial assessment of platelet reactivity (on DAPT and 1, 4 and 12 weeks post cessation). The primary outcome was platelet reactivity, expressed as platelet reactivity units (PRU) at each time point. 41 participants were included in this study, (23 ticagrelor, 18 prasugrel). There was no statistically significant differences in baseline characteristics between prasugrel/ticagrelor treated patients . The pattern of platelet reactivity recovery after DAPT cessation differed between the ticagrelor and prasugrel: with ticagrelor, after the initial PRU increase from baseline, the PRU remained stable, while with prasugrel, there was a further increase in PRU between 1 and 4 weeks, with a return to the 1 week level by 12 weeks (p = 0.034 for the time × treatment interaction between ticagrelor and prasugrel). Our results suggest there is a transient platelet hyper-reactivity after cessation of ADP receptor blockers therapy with prasugrel, but not ticagrelor. Further research is required to elucidate the pathophysiologic mechanisms behind these findings and to evaluate potential strategies to prevent or overcome this "rebound" effect.

The Effect of Mineralocorticoid Receptor Antagonists on Recruitment and Function of Endothelial Progenitor Cells in Patients with Congestive Heart Failure.

BACKGROUND: Circulating endothelial progenitor cells have an important role in the process of vascular repair. Impaired recruitment and function of endothelial progenitor cells is related to the pathophysiology of congestive heart failure. Endothelial progenitor cells have been shown to express the mineralocorticoid receptor. OBJECTIVES: To investigate the effect of mineralocorticoid receptor antagonists on endothelial progenitor cells in patients with heart failure. METHODS: Twenty-four patients with compensated heart failure, who were not under mineralocorticoid receptor antagonist therapy, were recruited. Either eplerenone (n=8) or spironolactone (n=16) therapy was initiated. Circulating endothelial progenitor cell level, identified as the proportion of mononuclear cells expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34, was evaluated by flow cytometry at baseline and after 8 weeks. Following 7 days of culture, colonies were counted by microscopy and MTT assay was performed on randomly selected patients (n=12) to estimate viability. RESULTS: Both median CD34+/VEGFR2+ and median CD133+/VEGFR2+ increased significantly (P = 0.04 and 0.02, respectively). However, the number of colonies and viability of the cells after therapy (as assessed by the MTT assay) was not significantly different compared with the baseline. CONCLUSIONS: These preliminary results suggest that mineralocorticoid receptor blockade may enhance endothelial progenitor cells recruitment in patients with compensated heart failure.

Characterization of surface antigens of reticulated immature platelets.

Reticulated platelets (RPs) are immature platelets with high dense granules content and a residual amount of megakaryocyte-derived of mRNA. Increased level of RPs has been found to be an independent predictor of cardiovascular ischemic events, and has been associated with impaired response to various anti-platelet drugs. The study aimed to characterize and compare the surface antigenic properties of reticulated versus mature platelets. Platelets from healthy individuals and diabetic patients were tested at rest and after activation with adenosine diphosphate (ADP). For each patient, we calculated the proportion of RPs and mature platelets using flow cytometry analysis with thiazole orange staining (for RPs) and CD42b platelet-specific antibody. We also tested the surface expression of P-selectin and Annexin V, by double staining flow cytometry in RPs versus mature platelets. A total of 20 subjects were recruited (10 healthy individuals, 10 diabetics). Activation with ADP did not cause a significant change in the proportion of RPs. Following activation, RPs demonstrated a significant increase in the expression of both P-selectin and Annexin V, while mature platelets exhibited a non-significant increase in both markers. These findings were consistent in both healthy subjects and patients with diabetes. In conclusion, RPs have a significantly higher capacity to increase the expression of platelet activation markers compared with mature platelets.

Long Term Outcomes of MGuard Stent Deployment in Saphenous Vein Grafts and Native Coronary Arteries: A Single Center Experience.

BACKGROUND: The MGuard™ stent (InspireMD, Tel Aviv, Israel) is a bare metal mesh-covered stent, developed to prevent no-reflow phenomenon during percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) and acute myocardial infarction (MI), both associated with significant atherothrombotic lesions. OBJECTIVES: To report on local experience with patients treated with the MGuard stent until follow-up at 1 year. METHODS: We followed 163 consecutive patients who underwent MGuard stent deployment during the period 2009 to 2014 in a large tertiary cardiac center in central Israel. RESULTS: The MGuard stent was used in 67% of patients who underwent SVG-PCI while 33% were treated for native coronary artery disease, the majority during ST-elevation MI (STEMI). The mean age was 67 years and 83% were males. The clinical presentation was STEMI in 30% and non-STEMI/unstable angina in 60% of patients. Of the total number of patients, 47% had diabetes and 29% had chronic kidney disease. All patients had follow-up at 1 year. Mortality in the native group was 1.9% vs. 10% in the vein graft cohort. ST was 2% in both groups. The major adverse cardiac event (MACE) rates were 11% in the native artery and 29% in the vein graft group, mainly due to respective target lesion revascularization/target vessel revascularization rates of 6% and 7% in the native vessel group and 11% and 15% in the SVG group. CONCLUSIONS: In suitable patients undergoing SVG-PCI or native lesion intervention during acute MI, the MGuard stent is a viable treatment strategy. Its potential merits and limitations warrant further evaluation.