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Item does not contain fulltext, BACKGROUND: COMBO (OrbusNeich Medical, Hong Kong) is a dual-therapy coronary stent featuring sirolimus as antiproliferative drug and an anti-CD34+ antibody coating to attract endothelial progenitor cells favoring rapid stent re-endothelization. The Mega COMBO collaboration aimed to evaluate the performance of the COMBO stent in a large contemporary cohort of patients undergoing percutaneous coronary intervention (PCI). METHODS: Patient-level data of subjects undergoing PCI with the COMBO stent from the REMEDEE-Trial, REMEDEE-OCT, HARMONEE, REDUCE, SORT OUT X, REMEDEE-Registry and MASCOT studies were pooled together. The primary endpoint was 1-year target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction (TV-MI) or clinically driven target lesion revascularization (CD-TLR). Secondary outcomes were the individual components of the primary endpoint and stent thrombosis (ST). Endpoints were evaluated against performance goals based on the EAPCI (the European Association of Percutaneous Coronary Intervention) recommendations for new drug-eluting stents. RESULTS: A total of 6753 patients (mean age 63.7 ± 11.4 years, 23% women) were included. At 1-year follow-up, TLF occurred in 303 (4.6%) patients. The rates of cardiovascular death, TV-MI, and CD-TLR were 1.3%, 1.8%, and 2.5%, respectively. The rate of definite/probable ST was 0.73%, early ST (<1 month) was 0.48%, while late ST (1-12 months) was 0.26%. The performance goals were met for all of the evaluated endpoints. CONCLUSIONS: This large patient-level pooled analysis provides a comprehensive outline of the performance of the dual-therapy COMBO stent. The low rates of primary and secondary endpoints suggest that this stent technology may be a good alternative to other contemporary drug eluting coronary stent platforms.

Item does not contain fulltext, BACKGROUND: Several reports have demonstrated the impact of the COVID-19 pandemic on the management and outcome of patients with ST-segment elevation myocardial infarction (STEMI). The aim of the current analysis is to investigate the potential gender difference in the effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI patients within the ISACS-STEMI COVID-19 Registry. METHODS: This retrospective multicenter registry was performed in high-volume primary percutaneous coronary intervention (PPCI) centers on four continents and included STEMI patients undergoing PPCIs in March-June 2019 and 2020. Patients were divided according to gender. The main outcomes were the incidence and timing of the PPCI, (ischemia time ≥ 12 h and door-to-balloon ≥ 30 min) and in-hospital or 30-day mortality. RESULTS: We included 16683 STEMI patients undergoing PPCIs in 109 centers. In 2020 during the pandemic, there was a significant reduction in PPCIs compared to 2019 (IRR 0.843 (95% CI: 0.825-0.861, p < 0.0001). We did not find a significant gender difference in the effects of the COVID-19 pandemic on the numbers of STEMI patients, which were similarly reduced from 2019 to 2020 in both groups, or in the mortality rates. Compared to prepandemia, 30-day mortality was significantly higher during the pandemic period among female (12.1% vs. 8.7%; adjusted HR [95% CI] = 1.66 [1.31-2.11], p < 0.001) but not male patients (5.8% vs. 6.7%; adjusted HR [95% CI] = 1.14 [0.96-1.34], p = 0.12). CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures similarly observed in both genders. Furthermore, we observed significantly increased in-hospital and 30-day mortality rates during the pandemic only among females. Trial registration number: NCT 04412655.

Item does not contain fulltext, BACKGROUND: The long-term prognostic implications of fractional flow reserve (FFR)-negative lesions hosting vulnerable plaques remain unsettled. AIMS: The aim of this study was to evaluate the association of non-ischaemic lesions hosting optical coherence tomography (OCT)-detected thin-cap fibroatheromas (TCFA) with first and recurrent cardiovascular events during follow-up up to 5 years in a diabetes mellitus (DM) patient population. METHODS: COMBINE OCT-FFR is a prospective, international, double-blind, natural history study. Patients with DM and with ≥1 FFR-negative lesion were classified into 2 groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint (PE) is a composite of cardiac mortality, target vessel-related myocardial infarction (TV-MI), clinically driven target lesion revascularisation (TLR), or unstable angina (UA) requiring hospitalisation during follow-up up to 5 years. RESULTS: Among 390 DM patients (age 67.5±9 years; 37% female) with ≥1 FFR-negative lesion, 292 (74.9%) were TCFA-negative while 98 (25.1%) were TCFA-positive. The PE occurred more frequently in TCFA-positive than in TCFA-negative patients (21.4% vs 8.2%, hazard ratio [HR] 2.89, 95% confidence interval [CI]: 1.61-5.20; p<0.001; 6.42 vs 2.46 events per 100 patient-years, rate ratio [RR] 2.61, 95% CI: 1.38-4.90; p=0.002). Furthermore, when TV-MI, TLR, and UA were treated as recurrent components of the PE, TCFA-positive patients experienced a higher risk of recurrent events (HR 2.89, 95% CI; 1.74-4.80; p<0.001; 13.45 vs 2.87 events per 100 patient-years, RR 4.69, 95% CI: 2.86-7.83; p<0.001). A multivariable analysis identified the presence of TCFA as an independent predictor of the PE (HR 2.76, 95% CI: 1.53-4.97; p<0.001). CONCLUSIONS: OCT-detected TCFA-positive lesions, although not ischaemia-generating, are associated with an increased risk of adverse events during long-term follow-up. CLINICALTRIALS: gov: NCT02989740.

Contains fulltext : 291566.pdf (Publisher’s version ) (Open Access), BACKGROUND: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. METHODS: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March-June 2019 and 2020. Patients were divided according to age (< or ≥75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. RESULTS: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825-0.861, p < 0.0001). We found a significant age-related reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24-1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05-1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic.

Item does not contain fulltext, AIMS: To study if any qualitative or quantitative optical coherence tomography (OCT) variables in combination with thin cap fibroatheroma (TCFA) patients could improve the identification of lesions at risk for future major adverse cardiac events (MACEs). METHODS AND RESULTS: From the combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) trial database (NCT02989740), we performed a detailed assessment OCT qualitative and quantitative variables in TCFA carrying diabetes mellitus (DM) patients with vs. without MACE during follow-up. MACEs were defined as a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and hospitalization for unstable angina. From the 390 fractional flow reserve (FFR)-negative DM patients, 98 (25.2%) had ≥1 OCT-detected TCFA, of which 13 (13.3%) had MACE and 85 (86.7%) were event-free (non-MACE). The baseline characteristics were similar between both groups; however, a smaller minimal lumen area (MLA) and lower mean FFR value were observed in MACE group (1.80 vs. 2.50 mm2, P = 0.01, and 0.85 vs. 0.89, P = 0.02, respectively). Prevalence of healed plaque (HP) was higher in the MACE group (53.85 vs. 21.18%, P = 0.01). TCFA were predominantly located proximal to the MLA. TCFA area was smaller in the MACE group, while no difference was observed regarding the lesion area. CONCLUSION: Within TCFA carrying patients, a smaller MLA, lower FFR values, and TCFA location adjacent to a HP were associated with future MACE. Carpet-like measured lesion area surface was similar, while the TCFA area was smaller in the MACE arm, and predominantly located proximal to the MLA.

Item does not contain fulltext, OBJECTIVE: The initial data of the International Study on Acute Coronary Syndromes - ST Elevation Myocardial Infarction COVID-19 showed in Europe a remarkable reduction in primary percutaneous coronary intervention procedures and higher in-hospital mortality during the initial phase of the pandemic as compared with the prepandemic period. The aim of the current study was to provide the final results of the registry, subsequently extended outside Europe with a larger inclusion period (up to June 2020) and longer follow-up (up to 30 days). METHODS: This is a retrospective multicentre registry in 109 high-volume primary percutaneous coronary intervention (PPCI) centres from Europe, Latin America, South-East Asia and North Africa, enrolling 16 674 patients with ST segment elevation myocardial infarction (STEMI) undergoing PPPCI in March/June 2019 and 2020. The main study outcomes were the incidence of PPCI, delayed treatment (ischaemia time >12 hours and door-to-balloon >30 min), in-hospital and 30-day mortality. RESULTS: In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio 0.843, 95% CI 0.825 to 0.861, p<0.0001). This reduction was significantly associated with age, being higher in older adults (>75 years) (p=0.015), and was not related to the peak of cases or deaths due to COVID-19. The heterogeneity among centres was high (p<0.001). Furthermore, the pandemic was associated with a significant increase in door-to-balloon time (40 (25-70) min vs 40 (25-64) min, p=0.01) and total ischaemia time (225 (135-410) min vs 196 (120-355) min, p<0.001), which may have contributed to the higher in-hospital (6.5% vs 5.3%, p<0.001) and 30-day (8% vs 6.5%, p=0.001) mortality observed during the pandemic. CONCLUSION: Percutaneous revascularisation for STEMI was significantly affected by the COVID-19 pandemic, with a 16% reduction in PPCI procedures, especially among older patients (about 20%), and longer delays to treatmen

Item does not contain fulltext, BACKGROUND: Autopsy studies have established that thin-cap fibroatheromas (TCFAs) are the most frequent cause of fatal coronary events. In living patients, optical coherence tomography (OCT) has sufficient resolution to accurately differentiate TCFA from thick-cap fibroatheroma (ThCFA) and not lipid rich plaque (non-LRP). However, the impact of OCT-detected plaque phenotype of nonischemic lesions on future adverse events remains unknown. Therefore, we studied the natural history of OCT-detected TCFA, ThCFA, and non-LRP in patients enrolled in the prospective multicenter COMBINE FFR-OCT trial (Combined Optical Coherence Tomography Morphologic and Fractional Flow Reserve Hemodynamic Assessment of Non-Culprit Lesions to Better Predict Adverse Event Outcomes in Diabetes Mellitus Patients). METHODS: In the COMBINE FFR-OCT trial, patients with diabetes and ≥1 lesion with a fractional flow reserve >0.80 underwent OCT evaluation and were clinically followed for 18 months. A composite primary end point of cardiac death, target vessel-related myocardial infarction, target-lesion revascularization, and hospitalization for unstable angina was evaluated in relation to OCT-based plaque morphology. RESULTS: A total of 390 patients (age 67.5±9 years; 63% male) with ≥1 nonischemic lesions underwent OCT evaluation: 284 (73%) had ≥1 LRP and 106 (27%) non-LRP lesions. Among LRP patients, 98 (34.5%) had ≥1 TCFA. The primary end point occurred in 7% of LRP patients compared with 1.9% of non-LRP patients (7.0% versus 1.9%; hazard ratio [HR], 3.9 [95% CI, 0.9-16.5]; P=0.068; log rank-P=0.049). However, within LRP patients, TCFA patients had a much higher risk for primary end point compared with ThCFA (13.3% versus 3.8%; HR, 3.8 [95% CI, 1.5-9.5]; P<0.01), and to non-LRP patients (13.3% versus 1.9%; HR, 7.7 [95% CI, 1.7-33.9]; P<0.01), whereas ThCFA patients had risk similar to non-LRP patients (3.8% versus 1.9%; HR, 2.0 [95% CI, 0.42-9.7]; P=0.38). Multivariable analyses identified TCFA as

Item does not contain fulltext, BACKGROUND: Gender differences in the thrombotic and bleeding risk have been suggested to condition the benefits of antithrombotic therapies in Acute Coronary Syndrome (ACS) patients, and mainly among those undergoing percutaneous coronary interventions with drug eluting stents (DES). The impact of gender on the optimal duration of dual antiplatelet therapy (DAPT) in ACS patients is still unexplored and was, therefore, the aim of the present sub-study. METHODS: REDUCE was a prospective, multicenter, randomized investigator-initiated study designed to enroll 1500 ACS patients after treatment with the COMBO Dual Stent Therapy, based on a noninferiority design. Patients were randomized in a 1:1 fashion to either 3 or 12 months of DAPT. Primary study endpoint was a composite of all-cause mortality, myocardial infarction, definite/probable stent thrombosis (ST), stroke, target-vessel revascularization (TVR) and bleedings (BARC II, III, V) at 12 months. Secondary endpoints were cardiovascular mortality and the individual components of the primary endpoint within 24 months. RESULTS: From June 2014 to May 2016 300 women and 1196 men were included in the study. Among them, 43.7% of females and 51.9% of males were assigned to the 3 months DAPT treatment. Baseline characteristics were well matched between the two arms, with the exception of a lower rate of TIMI flow < 3 (p = 0.04), lower systolic blood pressure (p = 0.05) and use of spironolactone (p = 0.006) among women and a more advanced age (p = 0.05) among men receiving a short-term DAPT. At a mean follow-up of 525 (± 198) days, no difference in the primary endpoint was observed according to DAPT duration in both females [6.9% vs 5.9%, HR (95% CI) = 1.19 (0.48-2.9), p = 0.71] and males [8.2% vs 9%, HR (95% CI) = 0.92 (0.63-1.35), p = 0.67; p INT = 0.20]. Results were confirmed after correction for baseline differences [females: adjusted HR (95% CI) = 1.12 (0.45-2.78), p = 0.81; males: adjusted HR (95% CI) = 0.90 (0.61-1.3

Item does not contain fulltext, AIMS: The aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. METHODS AND RESULTS: COMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99-10.89; P < 0.001). The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12-12.34; P < 0.001). CONCLUSIONS: Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients.

Item does not contain fulltext, Trained immunity (TI) is a proinflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and is characterized by immunometabolic and epigenetic changes that enhance cytokine production. Maladaptive activation of TI (ie, in the absence of infection) may result in detrimental inflammation and development of disease; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined. In this study, we uncovered the oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, [ECD]), characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production. Mechanistically, myeloid cells expressing BRAFV600E exhibit all molecular features of TI: activation of the AKT/mammalian target of rapamycin signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyperinflammatory responses. In patients with ECD, effective therapeutic strategies combat this maladaptive TI phenotype; in addition, pharmacologic inhibition of immunometabolic changes underlying TI (ie, glycolysis) effectively dampens cytokine production by myeloid cells. This study revealed the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation.

Contains fulltext : 233810.pdf (Publisher’s version ) (Closed access), BACKGROUND AND AIMS: The impact of advanced age on the optimal duration of dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary revascularization (PCI) is still greatly debated. Therefore, the aim of the present sub-analysis of the REDUCE trial was to assess the impact of age on the comparison between a short 3 months vs standard 12 months DAPT in ACS patients treated with the COMBO Dual Stent Therapy. METHODS: The REDUCE trial is a prospective, multicenter, investigator-initiated study that randomized ACS patients undergoing PCI with the COMBO drug eluting stent to either 3 or 12 months of DAPT. The study population was divided according to age (

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Contains fulltext : 220899.pdf (publisher's version ) (Open Access), Conflicting results have been reported so far in pooled analyses and studies evaluating the optimum duration of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients. However, randomized clinical trials dedicated to this specific setting of higher thrombotic risk patients have only recently been completed, pointing at the noninferiority of a shorter strategy as compared to the traditional 12-month DAPT, furthermore allowing to reduce the risk of major bleeding complications. Therefore, a reconsideration of current clinical practice and guidelines should be certainly be advocated in light of the most recent updates, especially among ACS patients treated with percutaneous coronary intervention (PCI) and modern drug-eluting stents (DES). Our aim was to provide a comprehensive review of the available evidence on the optimal DAPT duration in ACS patients.

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Contains fulltext : 202686.pdf (publisher's version ) (Open Access), BACKGROUND: ADP-antagonists such as prasugrel have reduced but yet not overcome the phenomenon of high-on treatment platelet reactivity (HRPR), that has been shown to increase the rate of major cardiovascular events after an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI). However, the exact prevalence and the principal determinants of suboptimal platelet inhibition in patients treated with dual antiplatelet therapy (DAPT) with prasugrel have not been completely clarified and were therefore the aim of the present study. METHODS: We included patients (<75 years and >60kg) treated with DAPT (aspirin+prasugrel) after PCI, mainly for an ACS. Platelet function test evaluation was performed at 1-3 months from discharge. HRPR was assessed by multiplate impedance aggregometry and defined for results above upper limit of normal after ADP stimulation. RESULTS: We included 190 post-ACS patients. HRPR with prasugrel was observed in 19 patients (10%). The prevalence of HRPR was stable in different high-risk subgroups of patients (female gender, hypercholesterolemic, and chronic kidney disease) whereas it was increased in diabetic patients (p=0.045), with a significant interaction between diabetic status and HRPR (p=0.04). However, at multivariate analysis, an impaired metabolic status, with higher levels of glycosylated hemoglobin and low-density lipoprotein (LDL) cholesterol, but not diabetic status, emerged as independent predictors of HRPR with prasugrel [OR (95% CI)=2.1 (1.32-3.33), p=0.002 and OR (95% CI)=1.03 (1.01-1.05), p=0.003, respectively], with a stronger linear relationship between ADP-mediated platelet aggregation and glycosylated hemoglobin levels (r=0.24, p=0.002), than for LDL-cholesterol (r=0.13, p=0.09). CONCLUSIONS: In post-ACS patients treated with PCI and receiving DAPT with prasugrel, HRPR is observed in about 10% of patients. Impaired metabolic status, and especially elevated glycosylated hemoglobin, emerged as independent predic

Contains fulltext : 202901.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, BACKGROUND: Acute coronary syndromes (ACS) represent a context of higher thrombotic risk, where larger advantages have been achieved by the administration of dual antiplatelet therapy (DAPT). However, the indication of 1year DAPT after coronary angioplasty for ACS has been supported by an outdated randomized trial (PCI-CURE). In addition, the initial fear of late thrombotic events emerged with first generation drug-eluting stents (DES), that suggested the need of a prolonged DAPT prescription, has been completely overcome by the recent technological evolution of DES, that have shown faster re-endothelization and lower rates of late thrombotic complications. By keeping in mind the balance between thrombotic and bleeding complications, and due to the paucity of dedicated randomized trials, the identification of the optimal duration of DAPT after ACS is still matter of debate, and is therefore the aim of the present meta-analysis. METHODS: Literature and main scientific session abstracts were searched. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. A pre-specified analysis was conducted according to the DAPT strategy allocation (<12 vs standard 12months duration and 6-12months vs extended DAPT). RESULTS: We included 3 RCTs and subanalyses from 8 RCTs, with a total of 17,941 patients. No difference in mortality was observed between shorter vs longer DAPT (OR[95%CI]=1.11[0.90,1.36], p=0.33; phet=0.76). A shorter DAPT duration significantly reduced the rate of major bleeding events (1.5%, vs 1.9%, OR [95%CI]=0.75 [0.60, 0.94], p=0.01; phet=0.43). The reduction in bleeding events was more significant in trials evaluating extended DAPT duration (OR[95%CI]=0.62[0.45, 0.85], p=0.003; phet=0.49). No difference in cardiovascular mortality, myocardial infarction and stent thrombosis was observed with shorter vs standard 12-moth DAPT, whereas a more extended treatment (beyond 1year), was associated with a significant re

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Item does not contain fulltext, BACKGROUND: Fractional flow reserve (FFR) currently represents the gold standard in the evaluation of the haemodynamic relevance of coronary stenoses. However, both intracoronary and intravenous adenosine may be tolerated poorly by some patients. Therefore, considerable interest had been focused in the last few years on new adenosine-free indexes to define the haemodynamic relevance of coronary stenoses. So far, few data have been reported on resting Pd/Pa and its correlation with FFR as evaluated with high-dose intracoronary adenosine administration, which is the aim of the current study. MATERIALS AND METHODS: FFR was assessed in 120 patients with 137 intermediate lesions during cardiac catheterization by a pressure-recording guidewire (PrimeWire). FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at hyperaemia. Intracoronary doses of adenosine were administered up to 720 mug as intracoronary boli. Exclusion criteria were as follows: (a) allergy to adenosine; (b) baseline bradycardia (heart rate <50 bpm); (c) hypotension (blood pressure <90 mmHg); and (d) refusal to provide signed informed consent. RESULTS: High doses of intracoronary adenosine were well tolerated, with no major side effects. Increasing doses up to 720 mug progressively decreased FFR values and increased the percentage of patients showing an FFR less than 0.80. Resting Pd/Pa showed good accuracy in the identification of patients with significant FFR values (<0.80) [area under the curve=0.9 (0.84-0.96), P<0.0001]. Using receiver-operating characteristic curves, we identified a threshold less than 0.93 as the best accurate cut-off value in the prediction of a positive FFR value. A value up to 0.88 was associated with a 100% positive predictive value, whereas a value of at least 0.95 was associated with a 95% negative predictive value. CONCLUSION: This study showed that in intermediate lesions, resting Pd/Pa was related linearly to FFR. We identified 0.93 as the b

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Item does not contain fulltext, BACKGROUND: Recent trials have failed to demonstrate any clinical benefit from pre-treatment with dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary interventions, (PCI), even in the setting of acute coronary syndrome. However, suboptimal platelet inhibition during (PCI) has been shown to enhance the risk of acute ischemic complications, such as stent thrombosis and periprocedural myocardial infarction (PMI), thus raising the attention on the potential advantages of adjunctive glycoprotein IIbIIIa inhibitors to obviate to the delayed onset of action of oral antiplatelet drugs. The aim of the present study was then to evaluate the impact of platelet reactivity and pre-procedural DAPT on PMI in patients undergoing PCI with adjunctive tirofiban. METHODS: In a consecutive cohort of patients undergoing PCI with tirofiban (intracoronary/intravenous+/-prolonged infusion), periprocedural myonecrosis was defined as troponin I increase by 3 times the ULN or by 50% of an elevated baseline value, whereas PMI as CKMB increase by 3 times the ULN or 50% of baseline. Platelet function was assessed by impedance aggregometry. RESULTS: A total of 168 patients were included, 77 (45.8%) of whom were on DAPT at the time of PCI. Patients on DAPT had more often a history of previous PCI (p=0.03), higher ACS at admission (p<0.001) and creatinine levels (p=0.03). Coronary calcifications and type C lesions were more frequent in patients without DAPT (p=0.02 and p=0.03, respectively), as much as TIMI flow<3 (p=0.03), while procedural characteristics were comparable. Baseline platelet reactivity was significantly reduced in DAPT treated patients (p<0.001 for ASPI, COL and ADP tests). However the rate of periprocedural myonecrosis did not differ according to pre-procedural DAPT (68.4%vs 67%, p=0.87; adjusted OR[95%CI]=1.34[0.71-2.53], p=0.36) and neither the occurrence of PMI (13.3% vs 12.6%, p=0.99; adjusted OR[95%CI]=1.24[0.51-3.1], p=0.64). Furthermore, baseline pla

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Item does not contain fulltext, Contrast-induced nephropathy (CIN) is a common complication of coronary angiography/percutaneous coronary intervention (PCI). Identification of high-risk patients and optimal periprocedural management are key points to reduce the incidence of this iatrogenic complication. We evaluated the impact of gender on CIN after coronary angiography/PCI. We enrolled 2851 consecutive patients (730 females and 1851 males) undergoing coronary angiography/PCI. Baseline clinical and procedural characteristics were collected according to gender. CIN was defined as an absolute >/=0.5mg/dL or a relative >/=25% increase in creatinine level 24 to 48 hours after the procedure. The incidence of CIN was 12.6% and was significantly higher among females (15.6% vs 11.4%, odds ratio (OR) [95% confidence interval (CI)] = 1.42 [1.11-1.82]; P = .004), but this result was not confirmed at multivariate analysis after correction for all baseline confounders (adjusted OR [95% CI] = 1.14 [0.81-1.60]; P = 0.45). In conclusion, we showed that female gender is associated with an increased risk of CIN after coronary angiography/PCI. However, this finding was not confirmed after correction for baseline confounders. Therefore, the higher risk profile rather than female gender itself may contribute to the higher occurrence of CIN among women.

Item does not contain fulltext, BACKGROUND: Statins represent a pivotal treatment in coronary artery disease, offering a reduction in cardiovascular risk even beyond their lipid-lowering action. However, the mechanism of these "pleiotropic" benefits of statins is poorly understood. Vitamin D has been suggested as a potential mediator of the anti-inflammatory, anti-thrombotic and vascular protecting effects of statins. Aim of present study was to assess the impact of a high-intensity statin therapy on vitamin D levels and platelet function in patients with coronary artery disease. METHODS: Patients discharged on dual antiplatelet therapy and high-intensity statins after an ACS or elective PCI were scheduled for main chemistry and vitamin D levels assessment at 30-90days post-discharge. Vitamin D (25-OHD) dosing was performed by chemiluminescence method through the LIAISON(R) Vitamin D assay (Diasorin Inc). Platelet function was assessed by Multiplate(R) (multiple platelet function analyser; Roche Diagnostics AG). RESULTS: Among 246 patients included, 142 were discharged on a new statin therapy or with an increase in previous dose (Inc-S), while 104 were already receiving a high-dose statin at admission, that remained unchanged (Eq-S). Median follow-up was 75.5days. Patients in the Inc-S group were younger (p=0.01), smokers (p<0.001), with a less frequent history of hypercholesterolemia (p=0.05), diabetes (p=0.03), hypertension (p=0.02), or previous cardiovascular events (p<0.001). They were more often admitted for an acute coronary syndrome (p<0.001) and used less anti-hypertensive drugs or nitrates. Higher total circulating calcium was observed in the Inc-S group (p=0.004), while baseline vitamin D levels were similar in the 2 groups (p=0.30). A significant reduction in the circulating low-density lipoprotein (LDL) cholesterol was observed in the Inc-S group. Vitamin D levels increased in the Inc-S patients but not in the Eq-S group (delta-25OHD: 23.2+/-20.5% vs 3.1+/-4.7%, p=0.003), with a linear

Item does not contain fulltext, BACKGROUND AND AIMS: Immature platelet fraction (IPF) represents the quote of younger and larger sized circulating platelets, a potential marker of platelet reactivity and major cardiovascular events. We aimed to assess the relationship between IPF levels and the prevalence and extent of coronary artery disease (CAD) in patients undergoing coronary angiography. METHODS: A cohort of consecutive patients undergoing coronary angiography in a single centre were included. Significant CAD was defined as at least 1 vessel stenosis >50%, while severe CAD was defined as left main and/or three-vessel disease. IPF levels were measured at admission by routine blood cells count (A Sysmex XE-2100). RESULTS: We included 1789 patients, divided according to quartiles values of IPF. IPF levels were directly related to active smoke (p = 0.02), and non-acute coronary syndrome as indication to angiography (p < 0.001), higher levels of haemoglobin and uric acid (p < 0.001, respectively) and lower platelet count (p = 0.003). Angiographic features did not significantly differ according to quartiles values of IPF, but for a lower degree of TIMI flow in patients with a higher percentage of reticulated platelets (p = 0.01) and a higher rate of lesions involving bifurcations (p = 0.05). IPF levels did not affect the prevalence of CAD (77% vs. 82.2% vs. 79.1% vs. 75.6%, p = 0.34, adjusted OR [95% CI] = 0.93 [0.82-1.05], p = 0.22), nor of severe left main/three-vessel CAD (28.5% vs. 34.4% vs. 32.2% vs. 33.1%, p = 0.27; adjusted OR [95% CI] = 0.99 [0.90-1.1], p = 0.88). CONCLUSIONS: The present study shows that among patients undergoing coronary angiography, the immature platelet fraction (IPF) is not associated with the prevalence and extent of coronary artery disease, and, therefore, should not be overlooked as a marker of coronary atherosclerosis.

Item does not contain fulltext, AIMS: The purpose of this study was to determine whether direct ambulance transport of ST-elevation myocardial infarction (STEMI) patients to a percutaneous coronary intervention (PCI) hospital (field triage) leads to a lower 30-day mortality compared to transport via a referral non-PCI hospital (referral via a spoke centre) in STEMI patients. METHODS AND RESULTS: We performed a systematic review of interventions. An experienced librarian searched in PubMed, EMBASE.com and The Cochrane Library (via Wiley) from January 1980-February 2013. Studies that examined field triage and/or referral via a spoke centre in STEMI patients treated with primary or facilitated PCI were included. Two authors independently conducted the study selection and data extraction. Multivariable frequency weighted logistic regression analysis was performed to assess the effect of the type of transfer on the outcome measures. We identified 14 randomised clinical trials (RCTs), including 20 transfer groups and 4474 participants. Thirty-day mortality was lower in patients who underwent field triage (3.0%; 95% confidence interval (CI) 2.2-4.2) compared to patients who were referred via a spoke centre (4.7%; 95% CI 4.0-5.5). In multivariable frequency weighted logistic regression analysis, field triage was independently associated with a lower incidence of 30-day mortality (odds ratio (OR): 0.58; 95% CI 0.37-0.89). CONCLUSION: Field triage compared to referral via a spoke centre leads to a lower 30-day mortality in STEMI patients. Therefore, direct ambulance transport to a PCI hospital should become the transfer type for STEMI patients.

Item does not contain fulltext, BACKGROUND: Several concerns have emerged about the higher risk of very late stent thrombosis (ST) with first generation drug-eluting stent (DES) especially among STEMI patients. Newer generation DES has demonstrated to reduce ST at mid-term follow-up. Therefore, the aim of the present study is to perform an individual patient's data meta-analysis of trials comparing 1st generation DES vs. 2nd generation DES (everolimus-eluting stent, EES) in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. METHODS: We performed a formal search of electronic databases (MEDLINE and CENTRAL) and scientific session presentations from January 2010 to June 2016. We included all completed randomized trials comparing 1st vs. EES for patient presenting with STEMI. RESULTS: Individual patients data were obtained from 3 trials, including a total of 1581 patients (686 or 43.4% randomized to 1st generation DES and 895 or 56.4% randomized to EES). At long-term follow-up (1584+/-588days), EES did not significantly reduce mortality (7.8.% vs 11.7%, HR [95%CI]=0.77 [0.52, 1.13], p=0.18, pheterogeneity=0.93), cardiac mortality (6.2% vs 7.6%, HR [95%CI]=0.90 [0.56, 1.44], p=0.65, pheterogeneity=0.85), and reinfarction (8.1% versus 11.2%, respectively; HR [95%CI]=0.74 [0.51, 1.07], p=0.11, pheterogeneity=0.52). However, EES significantly reduced the occurrence of ST (3.4% versus 6.1% respectively, HR [95%CI]=0.56 [0.32, 0.97], p=0.04, pheterogeneity=0.42) and target vessel revascularization (TVR) (14.2% versus 20.1%; HR [95%CI]=0.63 [0.42, 0.96], p=0.03, pheterogeneity=0.55). Landmark analysis showed more consistent benefits in ST with EES within 1year, whereas benefits in TVR were mostly observed later than 1year. CONCLUSIONS: The present pooled patient-level meta-analysis demonstrates that among STEMI patients undergoing primary PCI, EES as compared to 1st generation DES is associated with a significant reduction in ST and TVR at long-term follow-up.

Item does not contain fulltext, BACKGROUND: Patients with coronary artery disease who undergo stent implantation and have concomitant indication for long-term oral anticoagulation represent a considerable proportion of the overall population. To date there is still no consensus about the optimal antithrombotic strategy to choose in this kind of patients, due to the difficult balance between an increased risk of bleeding and thromboembolic complications. Therefore, the aim of this study was to perform a meta-analysis to evaluate the risk and benefits of triple antithrombotic therapy versus dual antithrombotic therapy in patients undergoing coronary stent implantation, requiring long-term oral anticoagulation. METHODS: We performed formal searches of PubMed, EMBASE, Cochrane central register of controlled trials and major international scientific session abstracts from January 1990 to September 2015 regarding the use of triple antithrombotic therapy (TT) versus dual therapy (DT) in patients undergoing percutaneous coronary stent implantation that required chronic oral anticoagulation. Data regarding study design, inclusion/exclusion criteria, number of patients, and selected endpoints was extracted by 2 investigators. Disagreements were resolved by consensus. RESULTS: Sixteen trials with a total of 21716 patients undergoing coronary stent implantation with indication to long term oral anticoagulation, were finally included. A total of 6950 received TT, whereas 14766 received DT alone. The follow-up period ranged from 180 to 730 days. Data regarding mortality were available in 21658 patients (99.7 %). All cause mortality was observed in 10.4 % patients in TT versus 16.3 % in DT (OR [95 % CI] =0.73 [0.66-0.80], p <0.001; p het <0.001). In addition, TT was associated with a reduced incidence of MI (6.4 versus 9.8 %, OR [95 % CI] = 0.74 [0.65-0.84], p < 0.001; phet < 0.001) and ischemic stroke (1.8 versus 3.9 %, OR [95 % CI] = 0.55 [0.45-0.68], p < 0.001; p het = 0.07). As expected, TT was associated wi

Item does not contain fulltext, BACKGROUND/AIMS: Coronary artery disease (CAD) is a major cause of mortality worldwide. Hyperhomocysteinemia has been identified as a risk factor for CAD due to increased thrombogenicity, oxidative stress status and endothelial dysfunction. Few data have been provided on the impact of diabetes on homocysteine and its relationship with the prevalence and extent of CAD in this high-risk subset of patients and therefore, this is the aim of this study. METHODS: Our population is represented by a consecutive cohort of patients undergoing coronary angiography at Azienda Ospedaliera-Universitaria, 'Maggiore della Carita', Novara, Italy from March 2007 to October 2012. RESULTS: Diabetes was observed in a total of 1,125 out of 3,534 patients. Diabetes was associated with more advanced age, hypercholesterolemia, arterial hypertension, renal failure, previous myocardial infarction, coronary revascularization (p < 0.001, respectively) and smoking (p = 0.001). Patients with diabetes were more frequently on angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium-antagonists, diuretics, statins (p < 0.001, respectively), and acetylsalicylic acid (p = 0.004). Patients with diabetes displayed higher creatinine and triglycerides (p < 0.001), but lower total and high-density lipoprotein-cholesterol (p < 0.001) and haemoglobin (p < 0.001). Diabetes was associated with a significantly higher prevalence and extent of CAD and more complex lesions at angiography, including calcified lesion, total occlusions, in-stent restenosis. No significant difference was found in total homocysteine (tHcy) levels between diabetic and non-diabetic patients (p = 0.2). No difference in the percentage of patients with tHcy above the third tertile (>/=18.2 nmol/ml) was observed between patients with or without diabetes (32.8 vs. 35%, p = 0.18; adjusted OR 0.88, 95% CI 0.73-1.05, p = 0.14). Among patients with diabetes, no significant association was found between tHcy

Contains fulltext : 168186.pdf (publisher's version ) (Closed access), Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease-specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on narcolepsy in a comprehensive and systematic way. Here, the first prospective web-based European narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of narcolepsy and related disorders, including clear phenotype characterization of subtypes of narcolepsy, more precise epidemiological data and knowledge on the natural history of narcolepsy, expectations about treatment effects, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials.

Contains fulltext : 172736.pdf (publisher's version ) (Closed access), Residual high-on treatment platelet reactivity (HRPR) has been associated with a 2-9 fold increased risk of acute ischemic events in patients with acute coronary syndromes or coronary stenting. However, the mechanism of suboptimal platelet inhibition are still poorly understood. Aim of present study was to evaluate the role of the percentage of reticulated platelets on HRPR with ticagrelor. In patients treated with ASA (100-160 mg) and ticagrelor (90 mg twice a day) platelet reactivity and the reticulated platelets fraction (immature platelets fraction, IPF) were assessed at 30-90 days after acute coronary syndrome. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined as ADP test >417 AU*min. Our population is represented by 190 patients, divided according to tertiles values of IPF (<2.5; 2.5-3.99; >/=4 %). Higher IPF was associated to a larger platelet volume and lower platelets count (p < 0.001), and inversely related with a history of previous coronary revascularization (p = 0.03). Twenty-one out of 190 (11.0 %) patients displayed HRPR. No difference in the levels of circulating IPF was found in patients with or without HRPR (p = 0.25), with no correlation between the rate of reticulated platelets and platelet reactivity at ADP test (r = -0.084, p = 0.26). In fact no association was observed between high levels of IPF and the occurrence of HRPR (adjusted OR[95 % CI] = 0.69[0.34-1,37], p = 0.28), even after correction for baseline differences. In patients treated with ticagrelor, the levels of circulating reticulated platelets assessed at 30-90 days post-ACS are not associated with platelet reactivity or the occurrence of HRPR.

Item does not contain fulltext, BACKGROUND AND AIMS: New antithrombotic therapies have significantly improved the outcomes of patients with acute coronary syndrome (ACS), where the introduction of ticagrelor has provided the greatest mortality benefits. However, ticagrelor treatment has been associated with a potential increase in the serum uric acid (SUA) levels, which may influence endothelial dysfunction and prothrombotic status, thereby affecting the risk of acute cardiovascular events in patients requiring dual antiplatelet therapy (DAPT). The present study aimed to compare the impact of antiplatelet agents such as ticagrelor or clopidogrel on SUA levels and their effect on platelet reactivity. METHODS AND RESULTS: We included patients admitted for ACS or elective percutaneous coronary intervention (PCI) and discharged with ASA (acetylsalicylic acid; 100-160 mg) and clopidogrel (75 mg) or ticagrelor (90 mg twice a day). Chemistry was assessed at admission (baseline) and after a 30-90-day period of DAPT (together with platelet reactivity). The absolute and percentage variations of SUA after DAPT introduction were considered. Multiple-electrode aggregometry was used to assess platelet function. A total of 378 patients were enrolled, with 145 treated with aspirin and clopidogrel (AC) and 233 with aspirin and ticagrelor (AT). The AC patients were older (p = 0.003) and more often showed elective PCI as an indication to DAPT (<0.001); they received chronic therapy with ARB (angiotensin II receptor blocker; p = 0.001), nitrates (p = 0.044), CCB (calcium channel blocker; p = 0.005) and diuretics (p = 0.044). The AT patients displayed a higher percentage of ACS diagnosis (p < 0.001) and received chronic therapy with ACE (angiotensin-converting enzyme) inhibitors (p = 0.001), beta blockers (p = 0.001) and statins (p = 0.013). The AC patients displayed higher platelet reactivity at COL (collagen) test, ASPI test and ADP (adenosine diphosphate) test (p = 0.03, 0.001 and <0.001, respectively) and a higher

Item does not contain fulltext, BACKGROUND AND AIM: High residual platelet reactivity (HRPR) is still an important challenge, despite the advent of new potent ADP-antagonists. Therefore it is of extreme importance to identify factors that can influence platelet activation. Serum uric acid (SUA) has been largely addressed in the past as a possible risk factor for coronary artery disease, with a possible association with platelets hyperreactivity. So far no studies have assessed the role of serum uric acid on the response to dual antiplatelet therapy. Therefore, the aim of our study was to evaluate the impact of uric acid levels on platelet function in patients treated with dual antiplatelet therapy (DAPT) with clopidogrel or ticagrelor. METHODS AND RESULTS: We scheduled for platelet function assessment at 30-90 days post-discharge patients treated with DAPT (ASA + clopidogrel or ticagrelor) for an ACS or elective percutaneous coronary intervention (PCI). Platelet function was assessed by whole blood impedance aggregometry (Multiplate((R))-Roche Diagnostics AG), HRPR was considered for ASPI test >862 AU( *)min (for ASA) and ADP test values >/=417 AU( *)min (for ADP-antagonists). RESULTS: We included a total of 493 patients (262 were on ASA and clopidogrel and 231 on ASA and ticagrelor). Patients were divided according to quartiles of serum uric acid levels measured at the time of platelet aggregation assessment (Group 1 <4.6 mg/dL, n = 114; Group 2, 4.7-5.8 mg/dL, n = 133; Group 3, 5.9-6.8 mg/dL, n = 124; Group 4, >6.9, n = 122). Patients with higher uric acid levels were older, more often smokers, with history of hypertension and previous coronary artery bypass surgery and renal failure and were more often on therapy with diuretics at admission. Patients with higher SUA had higher triglycerides and fibrinogen. Uric acid levels did not influence ASPI, COL, TRAP and ADP tests. High residual platelet reactivity (HRPR) was observed in 1.5% of patients treated with ASA, with no difference according to S

Contains fulltext : 172755.pdf (publisher's version ) (Closed access), Contrasting data have been reported so far on the role of reticulated platelets in suboptimal response to antiplatelet therapies. In particular, still unexplored is whether they may contribute to explain the higher risk of thrombotic complications observed in diabetic patients. Aim of the present study was to evaluate the impact of diabetes on the levels of reticulated platelets and its relationship with high residual on-treatment platelet reactivity (HRPR) in patients receiving dual antiplatelet therapy. In patients treated with ASA (100-160 mg) and clopidogrel (75 mg daily) or ticagrelor (90 mg twice a day) platelet reactivity and the reticulated platelets fraction (immature platelets fraction, IPF) were assessed at 30-90 days post-discharge for an acute coronary syndrome or elective PCI. Aggregation was assessed by multiple-electrode aggregometry. We included 386 patients, 158 (40.9 %) diabetics. The percentage of IPF was similar in diabetic and non diabetic patients, both at baseline (3.5 +/- 2.5 vs 3.6 +/- 2.7 %, p = 0.91) and at 30-90 days re-assessment (3.3 +/- 2.1 vs 3.5 +/- 2.5 %, p = 0.30), with diabetes not emerging as an independent predictor of IPF above III tertile (adjusted OR [95 %CI] = 0.58 [0.30-1.09], p = 0.10). Diabetic patients displayed an enhanced platelet reactivity and a higher rate of HRPR with ADP antagonists (32.8 vs 22.5 %, p = 0.009). However, no association was found between the percentage of IPF and platelet function (r = -0.004; p = 0.95 for ASPI test, r = -0.04; p = 0.59 for ADP-mediated aggregation), or the rate of HRPR for ADP antagonsist across IPF tertiles. Results were similar for diabetics both receiving clopidogrel and ticagrelor. Diabetic patients display a higher platelet reactivity and suboptimal response to ADP-antagonists. However, the rate of reticulated platelets is neither influenced by diabetic status nor associated with an increased platelet reactivity among diabetic patients receiving dual antiplatelet therapy for