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Frontline healthcare workers (HCWs) in hospitals have been among the most vulnerable members of the population since the COVID-19 pandemic, affecting not only physical but also mental health. Complementary approaches to providing information for HCWs on taking care of their mental health need development and scaling-up. Behaviorally designed interventions take into consideration the context, resistance, and impact in facilitating behavior change in a specific target segment towards an intended aspiration. The behaviorally designed interventions sought to build individual resilience aligned with the Mental Health and Psychosocial Support Services framework. These included strengthening the provision of non-specialized services and community support among the range of interventions that address mental health problems. These benefit the vulnerable sectors of the population who are at most risk of experiencing chronic stress. Scaling-up of low-cost and subtle tools is a worthy investment for government institutions to ensure that HCWs are continuously supported so they can continue to provide adequate and quality care to those afflicted by COVID-19.

Out-of-hospital cardiac arrest (OHCA) remains one of the principle challenges in the setting of critical care medicine and emergency cardiology. Areas covered: Long-term survival rates even after successful resuscitation are variable but increasing in the recent years; due to the improvement of base and advanced cardiac life support techniques an increasing number of resuscitated patients are admitted to the hospital. Recent data suggested that patients surviving to hospital discharge after OHCA presented long-term outcome similar to patients with ST-elevation myocardial infarction. However, limited and incompletely clear data are available in the literature about the selection and risk stratification of patients to be subjected to coronary angiography, particularly in patients who have unfavorable clinical features in whom procedures may be futile and may affect public reporting of morality. Recently the ESC and AHA addressed appropriate treatments for ST-elevation myocardial infarction (STEMI) patients with out-of-hospital cardiac arrest. Expert commentary: Immediate coronary intervention in the setting of OHCA appears to be associated with better survival to discharge; the documentation of an occluded coronary artery in medium 25% of patients without signs of STEMI at ECG helps to explain why early angiography can improve outcomes. In the treatment of OHCA we can find some ethical issues; for example a combination of comorbidities with advanced age and prolonged ischemia indicated by severe lactic acidosis may signify a high enough chance of multiorgan failure or anoxic brain injury and where the benefit of coronary reperfusion therapy appears minimal.

Contains fulltext : 215333.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, pinteraction=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p

Aims To systematically review literature comparing bare metal stent (BMS) to drug-eluting stent (DES) in end-stage renal disease (ESRD) patients on dialysis. ESRD patients on dialysis often suffer from accelerated atherosclerosis and higher rate of stent-related complications including major adverse cardiovascular events. Because dialysis usually qualifies ineligibility for randomized clinical trials, an evidenced-based stent choice for these patients is scarce. Methods PUBMED, CINHAL, COCHRANE, EMBASE and WEB OF SCIENCE were searched for studies comparing BMS vs. DES outcome in ESRD patients on dialysis. Results Twenty studies including 64 232 patients were considered. The use of DES was significantly associated with a reduction in all-cause mortality [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.76-0.89], death from a cardiovascular cause (OR 0.80, 95% CI 0.76-0.84) and target lesion revascularization/target vessel revascularization (OR 0.73, 95% CI 0.53-1.00). No significant difference was found in stent thrombosis (OR 1.08, 95% CI 0.50-2.33) and myocardial infarction incidence (OR 0.91, 95% CI 0.69-1.20). Conclusions Our meta-analysis shows a significant reduction in all-cause and cardiovascular mortality with the use of DES over BMS in dialyzed patients. Despite the lack of randomized studies, systematic use of DES in these high-risk patients should thus reasonably be considered as a first option in percutaneous coronary intervention candidates.

Introduction: Atherothrombosis and coronary artery disease affect more than 13 million individuals only in the United States, about 8 millions in Europe and are the major causes of death worldwide. In particular chronic stable angina impairs patient quality of life, is associated with an important health spending and increased patient mortality; it is a prominent symptom of coronary artery disease (CAD), the latter being prevalent worldwide in patients. A key role in pathophysiology of cardiovascular acute events is played by activated platelets. Aspirin and adenosine diphosphate antagonist in addition to it is recommended for 1 year for reduction of cardiovascular events in patients with prior myocardial infarction with a weak recommendation to continue thereafter. P2Y12 receptor antagonists, in addition to aspirin, have been shown in the last years, to reduce ischemic events in patients with acute coronary syndrome but their role in secondary prevention is still new and unclear. The aim of our paper is to review the long-term effect of therapy with ticagrelor on the basis of recent evidence based data. Methods: We performed an online search on the major search engines. All the randomized controlled trials were summarized in the table. Results: We included in our paper six randomized controlled trials and we mentioned about ten post – hoc analysis, sub studies and registries. All studies included the type the therapy and a mid or long term clinical follow up. Conclusions: The studies reported in our paper and in particular PEGASUS – TIMI 54 study showed the merit to placing attention of prevention secondary ischemic events after acute coronary syndrome in the context of treatment with dual anti – platelet therapy; it proved a clinical benefit in patients treated with ticagrelor (60 mg x 2) for 3 years. Nevertheless, the effectiveness of these results cannot be generalized to patients with higher bleeding risk or low ischemic risk. In fact prolonged therapy with ticagrelor 60 mg in combination with aspirin could be considered valuable in patients with repeated acute ischemic events or with several coronary revascularizations over time (especially in patients with lower bleeding risk).

Intracoronary thrombus is a common finding in acute coronary syndromes and often correlates with adverse prognosis and complications during percutaneous coronary interventions (PCIs). Bivalirudin, a direct thrombin inhibitor, is one of the recommended antithrombotic treatments for PCI in ST-elevation myocardial infarction (STEMI). The intracoronary administration of a bivalirudin loading dose, even if off-label, offers theoretical advantages over the standard intravenous route, providing a very high drug concentration in the infarct-related artery without increasing the total dose of the drug administered. After the description in case reports of such an approach, a larger scale experience was recently reported in a large cohort of patients with STEMI treated during primary PCI with a bivalirudin intracoronary loading dose followed by the standard intravenous maintenance infusion. As a control group, a propensity score-matched cohort of patients undergoing primary PCI treated with intravenous bivalirudin in the same institution was selected. Compared with the intravenous bolus, the intracoronary administration of bivalirudin was associated with improved ST-segment resolution, lower post-procedural peak CK-MB levels, and better Thrombolysis in Myocardial Infarction (TIMI) frame count values, without difference in bleeding rates. Thus, this new promising antithrombotic strategy, based on the intracoronary administration of a bivalirudin loading dose during primary PCI, appeared safe, improved myocardial reperfusion, and mitigated enzymatic myocardial infarct size compared with the standard intravenous protocol. Randomized trials are warranted to confirm these results and evaluate the possible long-term clinical benefits.

Summary Background Maternal vitamin D status has been associated with bone mass of offspring in many, but not all, observational studies. However, maternal vitamin D repletion during pregnancy has not yet been proven to improve offspring bone mass in a randomised controlled trial. We aimed to assess whether neonates born to mothers supplemented with vitamin D during pregnancy have greater whole-body bone mineral content (BMC) at birth than those of mothers who had not received supplementation. Methods The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial that recruited pregnant women from three study sites in the UK (Southampton, Oxford, and Sheffield). Eligible participants were older than 18 years, with a singleton pregnancy, gestation of less than 17 weeks, and a serum 25-hydroxyvitamin D (25[OH]D) concentration of 25–100 nmol/L at 10–17 weeks' gestation. P'articipants were randomly assigned (1:1), in randomly permuted blocks of ten, to either cholecalciferol 1000 IU/day or matched placebo, taken orally, from 14 weeks' gestation (or as soon as possible before 17 weeks' gestation if recruited later) until delivery. Participants and the research team were masked to treatment allocation. The primary outcome was neonatal whole-body BMC, assessed within 2 weeks of birth by dual-energy x-ray absorptiometry (DXA), analysed in all randomly assigned neonates who had a usable DXA scan. Safety outcomes were assessed in all randomly assigned participants. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN 82927713, and the European Clinical Trials Database, EudraCT 2007–001716–23. Findings Between Oct 10, 2008, and Feb 11, 2014, we randomly assigned 569 pregnant women to placebo and 565 to cholecalciferol 1000 IU/day. 370 (65%) neonates in the placebo group and 367 (65%) neonates in the cholecalciferol group had a usable DXA scan and were analysed for the primary endpoint. Neonatal whole-body BMC of infants born to mothers assigned to cholecalciferol 1000 IU/day did not significantly differ from that of infants born to mothers assigned to placebo (61·6 g [95% CI 60·3–62·8] vs 60·5 g [59·3–61·7], respectively; p=0·21). We noted no significant differences in safety outcomes, apart from a greater proportion of women in the placebo group with severe post-partum haemorrhage than those in the cholecalciferol group (96 [17%] of 569 mothers in the placebo group vs 65 [12%] of 565 mothers in the cholecalciferol group; p=0·01). No adverse events were deemed to be treatment related. Interpretation Supplementation of women with cholecalciferol 1000 IU/day during pregnancy did not lead to increased offspring whole-body BMC compared with placebo, but did show that 1000 IU of cholecalciferol daily is sufficient to ensure that most pregnant women are vitamin D replete, and it is safe. These findings support current approaches to vitamin D supplementation in pregnancy. Results of the ongoing MAVIDOS childhood follow-up study are awaited. Funding Arthritis Research UK, Medical Research Council, Bupa Foundation, and National Institute for Health Research.

Background Early escalation from clopidogrel to new generation P2Y12 inhibitors is common practice in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Real-world data about this strategy, however, are limited. Methods From 2012 to 2015, 1,057 consecutive STEMI patients treated with pPCI in an Italian hub-and-spoke network were prospectively included in an observational registry (RENOVAMI, ClinicalTrials.gov Identifier: NCT01760382). We compared the prevalence, predictive factors and in-hospital outcomes of patients escalated to a new generation P2Y12 inhibitor within the first 24 hours from pPCI with those continuing on admission antiplatelet therapy. Results In the first 24 hours after pPCI, 165 patients (15.6%) were escalated from clopidogrel to a new generation P2Y12 inhibitor, while de-escalation to clopidogrel was occasional (19 patients, 1.8%) and switch between new generation P2Y12 inhibitors was rare (8 patients, 0.8%, all from ticagrelor to prasugrel). Drug eluting stent use (adjusted odds ratio [OR], 2.19, 95% confidence interval [CI], 1.55–3.08, p = 0.0002) and impaired renal function (adjusted OR, 0.19, 95% CI, 0.05–0.77, p = 0.02) were the only independent predictive factors for the decision to escalate. After adjustment for potential confounders, escalation did not predict in-hospital outcomes, whereas the overall use of new generation P2Y12 inhibitors was correlated with a better in-hospital survival (adjusted hazard ratio, 0.47, 95% CI, 0.25–0.91, p = 0.03). Moreover, escalation did not influence bleeding rates. Conclusions In this prospective registry of STEMI patients treated with pPCI and contemporary antiplatelet therapy, early escalation to a new generation P2Y12 inhibitor appeared safe and did not significantly affect in-hospital bleeding rates.

Heart rate is a fundamental determinant of cardiac oxygen consumption and plays a pivotal role in the pathophysiology of chronic stable angina (CSA). Ivabradine selectively and specifically inhibits the sino-atrial If current, slowing selectively heart rate without other significant haemodynamic effects. The consequent clinical effects are a sinus rate reduction similar to that obtained with beta-blockers, but without the related haemodynamic side effects. Ivabradine clinical benefits have been demonstrated both in patients with stable coronary artery disease (CAD) with associated systolic left ventricular dysfunction or in patients with congestive heart failure (HF). In this review we focused on the pharmacology and clinical research about ivabradine in the context of anti-ischemic therapy for CAD patients. Actually most guidelines suggest ivabradine therapy as last resort antianginal drugs in patients with uncontrolled symptoms or excessive heart rate despite maximum tolerated beta-blockade. However, the peculiar pharmacologic effects of the drug suggest that most patients with CAD might benefit from adding ivabradine to their therapeutic schemata. In fact, even if the recently released main analysis of the SIGNIFY study seems not to support an employ of ivabradine in primary prevention, it is easy to imagine a future wider use of this drug in elderly patients with incomplete myocardial revascularization and in patients with total chronic coronary occlusions and failure or unacceptable risk for percutaneous or surgical coronary revascularization.

Cardiovascular diseases and in particular coronary atherosclerotic disease are the leading cause of mortality and morbidity in the industrialized countries. Coronary atherosclerosis has been recognized for over a century and it was the subject of various studies. Pathophysiological studies have unravelled the interactions of molecular and cellular elements involved in atherogenesis; during the last decades the basic research has focused on the study of the instability of atherosclerotic plaque. Plaque rupture and resulting intracoronary thrombosis are thought to account for most acute coronary syndromes including ST - segment elevation myocardial infarction and non ST - segment elevation myocardial infarction. This is a brief review of the pathophysiology of atherosclerotic plaque development.

Intracoronary bolus administration may provide high local bivalirudin concentration without changing the global dose, potentially offering a more favorable antithrombotic effect in the infarct related artery (IRA).The purpose of this study was to investigate the feasibility and safety of intracoronary bolus administration of bivalirudin followed by the standard intravenous infusion in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI).In 245 consecutive patients treated with primary PCI, bivalirudin bolus was given directly in the IRA, followed by a standard intravenous infusion. Clinical reperfusion markers, postprocedural coronary flow indexes, and bleeding events of the intracoronary group were compared with a propensity score-matched cohort of primary PCI patients (n=245) treated with the standard bivalirudin protocol of intravenous bolus and infusion.Higher rates of ⩾70% ST-segment resolution (72.7% vs 60.0%, p=0.004), lower postprocedural peak CK-MB levels (188.3±148.7 vs 242.1±208.1 IU/dl, p=0.025) and better Thrombolysis in Myocardial Infarction (TIMI) frame count values (14.7 vs 17.9, p=0.001) were observed in the IC bolus group compared with the standard intravenous bolus group. Rates of bleeding were similar between groups. Only three cases of acute stent thrombosis were observed, all in the intravenous bolus group (p=0.25).Intracoronary bivalirudin bolus administration during primary PCI is safe and improves ST-segment resolution, postprocedural coronary flow and enzymatic infarct size compared with the standard intravenous route.

BACKGROUND Intracoronary Abciximab administration during primary percutaneous coronary intervention (pPCI) could offer theoretical advantages over the intravenous route. Besides antiplatelet effects, Abciximab can modulate inflammation via cross-reactivity with GPIIb/IIIa, avb3, and aMb2 receptors. The aim of our study was to assess whether the Abciximab administration route could influence its anti-inflammatory effects. METHODS Eighty-nine consecutive ST elevation myocardial infarction patient candidates for pPCI were randomized to intracoronary (Group A-47 patients) or intravenous (Group B-42 patients) Abciximab bolus administration. The primary endpoint was the extent of inflammation, measured by C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1) and inter-cellular adhesion molecule 1 (ICAM-1) levels. This study is registered with ClinicalTrials.gov, NCT01757457. RESULTS Data are expressed in medians (interquartiles). In both groups, troponin levels were similar [baseline: 0.12 (0.03-0.94) vs. 0.27 (0.07-1.24) ng/ml, P = 0.73; postprocedural: 22.00 (14.75-69.43) vs. 31.96 (8.23-7.20) ng/ml, P = 0.83]. Both groups also showed similar baseline [0.31 (0.14-0.69) vs. 0.22 (0.09-0.59) mg/ml, P = 0.80] and postprocedural CRP levels [2.28 (1.37-4.23) vs. 2.16 (1.15-3.22) mg/dl, P = 0.69], similar baseline [272.5 (224.7-340.8) vs. 262.2 (221.2-306.4) ng/ml, P = 0.33] and postprocedural soluble ICAM-1 levels [281.5 (244.6-337.4) vs. 287.2 (226.9-359.2) ng/ml P = 0.71], and similar baseline [771.6 (620.9-971.0) vs. 748.6 (592.2-838.8) ng/ml, P = 0.30] and postprocedural soluble VCAM-1 levels [785.2 (671.6-947.1) vs. 745.9 (641.1-841.9) ng/ml, P = 0.17]. In-hospital and 6-month event rates were similar in the two groups. CONCLUSIONS Our study suggests that Abciximab has similar anti-inflammatory effects irrespective of the administration route. It is unlikely that the potential clinical benefits of intracoronary Abciximab can be related to modulation of integrin receptors.

Coronary artery disease is the major cause of mortality and morbidity in the industrialized countries; in the United States of America and in Europe, it is responsible for one of every six deaths per year. In the setting of ischemic heart disease, angina pectoris and chest pain, in particular, are the major causes of emergency department accesses. Angina pectoris is a clinical syndrome characterized by discomfort typically in the chest, neck, chin and left arm induced by physical exertion, emotional stress and cold and is relieved by rest or by taking of nitrates. The main targets of treatment of angina pectoris are to improve quality of life by reducing the frequency and the severity of symptoms, to increase functional capacity and to improve prognosis. Ranolazine is a recent antianginal drug with unique methods of action. It was approved by the US Food and Drug Administration in 2006 as add-on therapy in patients symptomatic for stable angina. With the inhibition of the late sodium current, Ranolazine protects against ion deregulation, prevents cellular calcium overload and the subsequent increase in diastolic tension without impacting heart rate and blood pressure. Short term clinical trials and patent research show that add on therapy with Ranolazine in patients with chronic stable angina significantly improves exercise duration, exercise time to angina and reduces the use of nitro glycerine. Long term clinical trials showed no significant differences in the rate of cardiovascular death and myocardial infarction in patients with non-ST segment elevation acute coronary syndromes but a reduction in terms of recurrent ischemia. Ranolazine is generally well tolerated and even if it increases the duration of QTc interval it is not associated with atrial and ventricular arrhythmias. Therefore Ranolazine represents a good therapeutic approach in patients with chronic stable angina still symptomatic, while on optimal anti-ischemic therapy, or intolerant to traditional anti-ischemic drugs.

Objectives To perform an updated meta-analysis comparing biodegradable polymer drug eluting stents (BP-DES) and durable polymer drug eluting stents (DP-DES). Background BP-DES have been suggested to reduce late stent thrombosis (LST) rates as compared to first generation DP-DES. Recently, second generation DP-DES have replaced older DES, but comparison of these stents with BP-DES has not yielded consistent results. Methods Medline/Web databases were searched for studies comparing BP-DES and DP-DES, and reporting rates of overall/cardiac mortality, myocardial infarction (MI), LST, target lesion revascularization (TLR) and target vessel revascularization (TVR) and late lumen loss (LLL), with a follow-up ≥6 months. Results Twenty studies (20,005 patients) were included in the meta-analysis. Median follow-up time was 1 year. Compared with DP-DES, BP-DES showed lower LLL (in stent: weighted mean difference WMD −0.45 mm, 95% CI −0.66 to −0.24 mm, P = 0.00001; in segment: WMD −0.15 mm, 95% CI = −0.24 to −0.06 mm, P = 0.001) and lower rates of LST (OR 0.51, 95% CI = 0.30 to 0.86, P = 0.01), although they did not improve mortality, MI, TLR, and TVR rates. BP-DES coated with sirolimus or novolimus, in comparison with biolimus or paclitaxel, were associated with reduced LLL (P

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA

Drug eluting balloons (DEB) have been developed to overcome the limitations of drug eluting stents (DES), but clinic results of various DEB studies are still not consistent. Thus, we performed a meta-analysis to compare outcomes of DEB and DES for the treatment of coronary artery disease (CAD).Medline/Web databases were searched for studies comparing DEB and DES for obstructive CAD, reporting late lumen loss (LLL) and rates for overall mortality, myocardial infarction (MI), stent thrombosis (ST) and target lesion revascularization (TLR).8 studies (1462 patients) were included in the meta-analysis. Compared with DES, DEB treated patients showed non-significantly higher LLL (weighted mean difference [WMD] 0.32, 95% confidence interval [CI] -0.15 to 0.78, P=0.18) and non-significantly higher rate of binary restenosis (odds ratio [OR] 1.40 [0.68-2.48], P=0.36). Mortality (OR 1.13[0.54-2.37], P=0.74), MI (OR 0.95, [0.50-1.80], P=0.87), ST (OR 1.12, [0.34-4.19], P=0.77) and TLR rates (OR 1.19[0.60-2.38], P=0.61) were similar between the 2 treatments. A pre-specified meta-regression analysis showed that LLL WMD and TLR OR were inversely correlated to the prevalence of diabetes (P0.0001) and directly correlated to reference coronary diameters (P0.001).The present meta-analysis showed that compared to DES, DEB use resulted in similar clinical efficacy and safety. Thus DEB could be considered a reasonable alternative to DES for the treatment of CAD in selected clinical settings (Clinicaltrials.gov identifier: NCT01760200).

ST-elevation and non-ST-elevation myocardial infarction (STEMI, NSTEMI) are considered two distinct pathophysiologic entities. We evaluated cardiac troponin I (cTnI) release in STEMI and NSTEMI using a "contemporary" (CV10 to 20% at the 99th percentile concentration) cTnI assay for patients undergoing early percutaneous coronary intervention (PCI).856 patients with suspected acute coronary syndrome consecutively admitted to the Emergency Department of the Maggiore Hospital of Novara (225 STEMI and 135 NSTEMI) were selected according to: 1) early (≤ 4 h from admission) and successful PCI; and 2) cTnI measurements at ED presentation and within 24h. The influence of the MI type on cTnI concentrations at baseline and after PCI as well as the velocity of cTnI [cTnI V=absolute increase (after log conversion of cTnI measurements)/delay between the two measurements] was studied by multiple regression analysis, adjusting for patient parameters.A statistically significant interaction between MI type and time from symptoms was reported on cTnI concentrations (p0.0001): STEMI and NSTEMI differed for cTnI releases at admission and after revascularization. Higher cTnI V in STEMI was detectable in patients admitted within 6h from symptoms. Baseline cTnI concentrations were lower in patients with a history of coronary artery disease (CAD) and increased with aging (p0.0001). In the elderly (75 years), the cTnI V was significantly increased.STEMI and NSTEMI patients have different patterns and dynamics of cTnI release influenced by the interaction with time from symptoms, by aging and history of CAD.

The direct thrombin inhibitor bivalirudin has gained popularity in cardiovascular medicine over the past decade because, in comparison with unfractionated heparin, it guarantees a predictable dose-related degree of anticoagulation with a low immunogenic profile and, possibly, with reduced rates of major bleeding complications. In the past bivalirudin has been frequently employed in the management of patients with heparin-induced thrombocytopenia. The REPLACE-2, ACUITY and ISAR-REACT4 studies demonstrated bivalirudin non-inferiority in comparison with unfractionated heparin in terms of ischemic end-points with a reduction of the bleeding rate also in patients acute coronary syndrome without ST elevation. Finally the results of the HORIZONS-AMI study positioned this drug as a first choice anticoagulant during percutaneous coronary interventions in patients with ST-elevation myocardial infarction. In fact the bivalirudin alone regimen, compared to unfractionated heparin plus GP2b3a inhibitors, decreased inhospital bleeding rates and short and long term mortality. Given the body of clinical evidence, bivalirudin is likely to contend to GP2b3a inhibitors the leading place among the proposed anticoagulation strategies in the setting of acute coronary syndromes. The duration of the bivalirudin infusion after PCI and the optimal oral antiplatelet regimen associated to bivalirudin are important issues to be solved in future randomized controlled studies.

Background Data on the correlations between biomarkers to suggest cost-effective multi-marker (MM) panels predictive for ST-elevation myocardial infarction (STEMI) patients are lacking. We sought to explore the relationship between cardiac troponin I (cTnI), C-reactive protein (CRP), B-type natriuretic peptide (BNP), and chromogranin A (CgA) accounting for biomarkers' profiles detected within 48 h from successful primary percutaneous coronary intervention (PPCI). Methods In 73 STEMI patients cTnI, CRP, BNP, and CgA were measured before PPCI and 6, 24, and 48 h later. STATIS methods generalizing Principal Component Analysis on three-way data sets were employed to extract information about: 1) similarities between patients, 2) contribution of each time of sampling and 3) correlations between biomarkers' profiles. Results STEMI patients who underwent successful PPCI emerged to have a homogeneous profile tailored on biomarkers' evaluation within 48 h. Their measurements at 24 h contributed the most variability and information both to patients' and to biomarkers' profiles. BNP and cTnI were highly correlated and explained the 40.1% of the total variance, whereas CgA resulted independent and explained the 26.3% of the total variance. Conclusions Markers' measurements at 24 h after PPCI contributed most information to the definition of patients' profile. BNP and cTnI resulted interchangeable in a MM panel for reporting about the extent of necrosis.

Background Skeletal myoblasts (SkMs) has provided a promising treatment for myocardial infarction (MI). Functioning as posttranscriptional regulators, microRNAs (miRNAs) play important roles in cardiac repairment and stem cell regulation. However, the correlation between miRNAs and their targeted genes in SkM cell therapy for MI was not fully understood. Methods We explored the cardioprotection by SkMs in infracted rats and determined cardiac functions at 4 weeks. In addition, we compared the expression profiles of miRNAs and mRNAs in post-MI rats with or without SkM cell therapy using microarray. The concordance between miRNA expression and mRNA levels of potential target genes was confirmed by quantitative real-time PCR. Results Quantitative echocardiography and histology showed improved cardiac function, attenuated heart infarcted area and inhibited cardiomyocyte apoptosis in the SkM group, compared with MI group. We identified that 160 miRNAs were differentially expressed in MI group as compared to the control group and 78 miRNAs were differentially expressed in the SkM treated group as compared to the untreated post-MI. We focused on a novel set of apoptosis-associated miRNAs and their target genes, among which 4 miRNAs (miR-30a-5p, miR-30c-5p, miR-145-5p, miR-140-3p), except one (miR-143-3p), were downregulated in the SkM treated group as compared to the untreated group. Furthermore, we found seven genes including Angptl4, Dpep1, Egr1, Eif5a, Tsc22d3, Irs2 and Cebpb that showed a linear correlation with which miRNAs. Conclusions The downregulation of apoptosis-regulatory miRNAs and in turn upregulation of target genes may partially account for rescue effect of SKM therapy for MI. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0603-0) contains supplementary material, which is available to authorized users.

The aim of this retrospective study was to map the specific ischemic lesion patterns of distribution in patent foramen ovale-related stroke (PFO-stroke) and atrial fibrillation-related stroke (AF-stroke) in patients with idiopatic ischemic stroke. 750 ischaemic strokes were screened on basis of diagnostic imaging and tests: patients with known causes were excluded. 171 patients with unknown cause were selected and divided in two groups: AF-stroke (43 patients) and PFO-stroke (128 patients). Vascular territories of ischemic involvement were divided into four classes in each group: the anterior cerebral artery, the middle cerebral artery, the vertebro-cerebral artery (including the posterior cerebral artery) and multisite (MS) involvement. Infarcts in vertebro-basilar territory and multisite represented each one about 32% of infarcts in PFO-stroke group and their involvement are more frequent than AF-stroke group (p = 0.03). Ischemic lesions in PFO-group were predominantly cortical (34.3%), and in AF-group cortical-subcortical (60.4%). Multisite pattern of ischemic lesion was more frequent in patients with severe degree of right to left shunts (37.5%). In clinical practice, PFO may be considered a cause of cortical stroke on the basis of radiological findings, when VB vascular territory or MS brain involvement is present in younger patients (

Background Pre-hospital ticagrelor, given less than 1 h before coronary intervention (PCI), failed to improve coronary reperfusion in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. It is unknown whether a longer interval from ticagrelor administration to primary PCI might reveal any improvement of coronary reperfusion. Methods We retrospectively compared 143 patients, pre-treated in spoke centers or ambulance with ticagrelor at least 1.5 h before PCI (Pre-treatment Group), with 143 propensity score-matched controls treated with ticagrelor in the hub before primary PCI (Control Group) extracted from RENOVAMI, a large observational Italian registry of more than 1400 STEMI patients enrolled from Jan. 2012 to Oct. 2015 ( ClinicalTrials.gov id: NCT01347580 ). The median time from ticagrelor administration and PCI was 2.08 h (95% CI 1.66–2.84) in the Pre-treatment Group and 0.56 h (95% CI 0.33–0.76) in the Control Group. TIMI flow grade before primary PCI in the infarct related artery was the primary endpoint. Results The primary endpoint, baseline TIMI flow grade, was significantly higher in Pre-treatment Group (0.88 ± 1.14 vs 0.53 ± 0.86, P = 0.02). However in-hospital mortality, in-hospital stent thrombosis, bleeding rates and other clinical and angiographic outcomes were similar in the two groups. Conclusions In a real world STEMI network, pre-treatment with ticagrelor in spoke hospitals or in ambulance loading at least 1.5 h before primary PCI is safe and might improve pre-PCI coronary reperfusion, in comparison with ticagrelor administration immediately before PCI.

Background The treatment of bifurcation lesions remains a challenge with poor immediate results and higher restenosis rate than in nonbifurcated lesions. Drug-eluting stents improve the outcome after coronary stenting, but are associated with a small but statistically significant increase in late and very late stent thrombosis. Thus, aim of the present study was to evaluate the angiographic and clinical results of a new type of stent (coated with murine monoclonal antihuman CD34 antibodies designed to attract circulating endothelial progenitor cells to rapidly establish a functional endothelial layer and promote healing stent implantation) in a cohort of consecutive patients with coronary bifurcation lesions. Methods and results Between December 2007 and July 2008, a total of 43 consecutive patients were enrolled and 47 consecutive bifurcation lesions were treated with endothelial progenitor capture cell stents. The angiographic end points binary restenosis rate inside the stent (within 5 mm of the stent edges or in the segments treated with balloon angioplasty) was 5% (2.1% in the main branch and 10.5% in the side branch). No stent thrombosis was observed. Clinical follow-up was completed in all patients at mean time of 34.5 days after percutaneous coronary interventions by clinical evaluation and 12.3 months with a telephone contact. Angina at rest was present in 3 patients (7.9%). No in-hospital, 30-days, or 12-months major adverse cardiac events (death, myocardial infarction, and repeat revascularization coronary artery bypass graft or percutaneous coronary angioplasty) were reported. Conclusions The use of endothelial progenitor capture cell in the setting of coronary bifurcation appears to be feasible and safe with no incidence of late stent thrombosis and a very low rate of repeated revascularization.

Plasma fibrinogen levels influence restenosis following elective percutaneous coronary intervention (PCI) for stable angina. It is unknown whether the same is true in the setting of primary PCI. The aim of the study was therefore to assess whether fibrinogen levels were associated to 6-month in-stent restenosis (ISR) in STEMI patients undergoing successful primary PCI. From January 2003 to October 2004, 267 patients were admitted to our Institution for STEMI and treated by primary PCI. Of these, 171 patients met the inclusion criteria and were enrolled in our study. Fibrinogen levels were assessed at admission, 12 h, 24 h, 48 h, 72 h following PCI and at discharge. Six-month angiographic follow-up was 100% complete. Subjects with 6-month ISR showed higher fibrinogen levels than patients without ISR. Patients in the upper fibrinogen tertile showed a higher 6-month incidence of symptoms and/or inducible myocardial ischemia (27.1% vs. 7.1%, P = 0.006) and a larger late lumen loss (1.3 ± 0.8 vs. 1.0 ± 0.9 mm, P = 0.049). Logistic regression analysis demonstrated a significant and independent association between fibrinogen levels and ISR. Our study suggests that increased plasma fibrinogen levels are related to ISR in STEMI patients undergoing primary PCI. Larger studies are warranted to assess the prognostic value of fibrinogen over harder end-points.

Coronary artery diseases continue to be the most common causes of mortality and morbidity in the industrialized world, especially in the setting of acute myocardial infarction. Platelets play a crucial role in thrombosis and haemostasis, which can be either beneficial or deleterious, depending on the circumstances. Platelet hyperreactivity is a multifactor process depending on genetic polymorphism, pathological state and lifestyle; it contributes to the activation of the thrombotic cascade. Under pathophysiological conditions platelets activation plays a critical role in arterial thrombosis including platelets aggregation, the basis of destabilization of coronary plaque. Despite the benefits observed in outcome when primary angioplasty is compared with thrombolysis for the treatment of acute myocardial infarction there is still some room for improvement; unfortunately the restoration of an “optimal” epicardial flow is not always related to an “optimal” myocardial reperfusion. In the recent, past several studies have shown significant benefits with the administration of glycoprotein IIb/IIIa inhibitors. Thus, the aim of the present review is to perform an update on factors associated with platelets hyperactivity and on adjunctive glycoprotein IIb – IIIa inhibitors in primary angioplasty.

Background: Evidence supporting the use of drug-eluting stents (DES) in saphenous vein graft (SVG) disease is uncertain. Previous studies have suggested that DES might reduce the re-intervention rate in SVG disease, with conflicting data on mortality. Thus, a meta-analysis was performed to compare outcomes of DES vs. bare metal stent (BMS) in SVG disease. Methods and Results: Medline and Web databases were searched for studies comparing DES and BMS for SVG disease, reporting rates of overall mortality, target vessel revascularization (TVR) and myocardial infarction (MI) with a follow-up of ≥6 months. The meta-analysis included 23 studies (7,090 patients). Compared with BMS, DES-treated patients had lower rates of TVR (odds ratio (OR), 0.53; confidence interval (CI), 0.39-0.72; P

Aortic valve atresia with interruption of the aortic arch is an extremely rare anomaly; only eleven cases of this anomaly have been reported to date. In the absence of additional sources of blood flow to the ascending aorta, aortic valve atresia with interruption of the aortic arch is fatal. We present, to the best of our knowledge, the first case of a live birth with aortic valve atresia and interrupted left aortic arch (type B) without evidence of an aorticopulmonary communication or ductal supply to the native ascending aorta. Instead, blood flow to the native aortic root was derived from a persistent right embryonic dorsal aorta.

The no - reflow phenomenon occurs in one third of the patients treated with primary percutanous intervention for acute ST segment elevation myocardial infarction. In addition of the effect of prolonged ischaemia, also reperfusion injury contributes significantly to the microvascular damage in the perfusion territory of the infarct - related coronary artery. In the recent years there has been an increasing interest in the concept of adjunctive mechanical thrombectomy to improve outcomes in primary percutaneous coronary intervention. In the literature randomized trials of thrombectomy have provided conflicting results with no definitive evidence for efficacy. The recently published Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (the largest randomized study of a thrombectomy device) demonstrates that adjunctive treatment with aspiration and manual thrombectomy improves clinical end - point. The aim of the report is to review the evidence to our date on the role of mechanical thrombectomy during primary percutaneous intervention in the setting of acute myocardial infarction.

Developing and mature midbrain dopamine (DA) neurons express fibroblast growth factor (FGF) receptor-1 (FGFR1). To determine the role of FGFR1 signaling in the development of DA neurons, we generated transgenic mice expressing a dominant negative mutant [FGFR1(TK-)] from the catecholaminergic, neuron-specific tyrosine hydroxylase (TH) gene promoter. In homozygous th(tk-)/th(tk-) mice, significant reductions in the size of TH-immunoreactive neurons were found in the substantia nigra compacta (SNc) and the ventral tegmental area (VTA) at postnatal days 0 and 360. Newborn th(tk-)/th(tk-) mice had a reduced density of DA neurons in both SNc and VTA, and the changes in SNc were maintained into adulthood. The reduced density of DA transporter in the striatum further demonstrated an impaired development of the nigro-striatal DA system. Paradoxically, the th(tk-)/th(tk-) mice had increased levels of DA, homovanilic acid and 3-methoxytyramine in the striatum, indicative of excessive DA transmission. These structural and biochemical changes in DA neurons are similar to those reported in human patients with schizophrenia and, furthermore, these th(tk-)/th(tk-) mice displayed an impaired prepulse inhibition that was reversed by a DA receptor antagonist. Thus, this study establishes a new developmental model for a schizophrenia-like disorder in which the inhibition of FGF signaling leads to alterations in DA neurons and DA-mediated behavior.

The effects of HSV-1 amplicon and polyethyleneimine (PEI)-mediated transfection of dominant negative FGF receptor-1 mutant FGFR1(TK-) into the rat brain substantia nigra (SN) were examined in vivo to model the reduced FGF signaling documented to occur in Parkinson's disease. The number of SN neurons that expressed tyrosine hydroxylase (TH) was significantly reduced following HSV-1 FGFR1(TK-) intranigral delivery and similar changes were observed after PEI-mediated FGFR1(TK-) transfections. Further, we also observed a significantly lower striatal dopamine content following the PEI transfection of FGFR1(TK-). Thus, we conclude that reduced FGF signaling in the SN of Parkinsonian patients could play a role in the impaired dopaminergic transmission associated with the degenerative disease.

Transradial percutaneous coronary interventions (PCIs) have gained popularity because of reduced vascular complications and increased patient acceptability. However, safety and efficacy of transradial PCI in ST elevation myocardial infarction has been questioned. Anomalous radial artery anatomy is a relatively common cause of transradial PCI failure. The authors describe a case of a primary PCI performed by transradial approach through a very small caliper and tortuous superficial brachioradial artery (a rare variant). The use of miniaturized and hydrophilic apparels allowed procedure success without significant delay. To the authors’ knowledge, this is the first report of a primary PCI performed through an abnormal superficial brachioradial artery with final success.

Cardiovascular disease, in particular acute coronary syndromes (ACS), is still one of the leading causes of death in industrialized countries. ACS including ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UA) are associated with lower mortality if diagnosed early. The diagnosis is based on clinical symptoms, ECG and circulating biomarker-level changes. Recent studies have shown that there are alternatives to the known biomarkers such as ultrasensitive troponin I or T and creatine kinase Mb; there are, in fact, novel biomarkers such as miRNAs. These are 22-nucleotide-long non-coding RNAs that regulate gene expression at post-transcriptional level. Several recent studies have shown that miRNAs play a physiological role in cardiovascular homeostasis and in the pathogenesis of cardiovascular disease. Expression-pattern studies of myocardial tissue reveal that several miRNAs are up- or down-regulated during myocardial infarction. The purpose of the present review is to highlight the state of the art and future views on this topic.

Intra-aortic balloon counterpulsation is the most widely used form of mechanical hemodynamic support in the setting of cardiogenic shock due to ST-segment elevation myocardial infarction (STEMI). Intra-aortic balloon pump (IABP) is also strongly recommended (class 1b) in the current European guidelines for treatment of STEMI. The evidence of a possible benefit of IABP in this setting is based mainly on registry data and a few randomized trials. Cardiogenic shock and subsequent death due to STEMI result from three factors: hemodynamic deterioration, occurrence of multiorgan dysfunction and systemic inflammatory response. IABP does not cause an immediate improvement in blood pressure, but the recent SHOCK II trial shows positive effects on multiorgan dysfunction. Some experimental and clinical studies have indicated that IABP results in hemodynamic benefits as a result of afterload reduction and diastolic augmentation with improvement of coronary perfusion. However, the effect on cardiac output is modest and may not be sufficient to reduce mortality. Furthermore we can say that the use of IABP before coronary revascularization in the setting of STEMI complicated with cardiogenic shock may make the interventional procedure safer by improving left ventricular unloading. The purpose of the present review is to clarify the state of the art on this topic.

A multicenter, open-label prospective trial was performed to determine the clinical and microbiologic efficacy of ofloxacin (OFLX) otic solution in the treatment of subjects > or =12 years with chronic suppurative otitis media (CSOM) and a chronically perforated tympanic membrane in the infected ear(s). A total of 207 patients at 27 centers in the United States and Central America received OFLX 0.5 mL instilled ototopically twice daily for 14 consecutive days. The primary clinical end point was cure (dry ear) or failure (not dry ear). The primary microbiologic end point was eradication of baseline pathogens. Because there was no comparator and there were few data in the literature regarding clinical efficacy in patients treated with other regimens, the efficacy of OFLX was compared with data recorded in the clinical records of historical-practice control (HPC) or current-practice control (CPC) subjects. The incidence of clinical cure in clinically evaluable OFLX-treated patients (91%; 148 of 162 subjects) was significantly higher than in HPC subjects (67%; 124 of 185 subjects) or CPC subjects (70%; 38 of 54 subjects). OFLX eradicated all baseline pathogens isolated in microbiologically evaluable subjects. These pathogens were predominantly Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis. The most common treatment-related adverse event, bitter taste, occurred in 17% (35 of 207) of OFLX-treated subjects. Thus OFLX 0.5 mL administered twice daily for 14 days was effective in resolving the signs and symptoms of CSOM in subjects > or =12 years, was significantly more effective than therapies used to treat HPC or CPC subjects, and was well tolerated.

We report an infant with hypoplastic left heart syndrome consisting of mitral valvar atresia, aortic valvar atresia, hypoplasia of the aortic arch and coarctation of the aorta, who demonstrated respiratory failure and global hypotonia, and who was eventually diagnosed with spinal muscular atrophy.

The aim of this study was to determine the diagnostic accuracy of technetium-99m tetrofosmin myocardial imaging for the localization of coronary artery stenoses of different degrees of severity. Stress-rest single-photon emission tomography (SPET) was performed on separate days in 80 patients (64 males, 16 females; mean age 61 years; 43 patients with previous myocardial infarction; 18 patients with pharmacological stress), within 6 months of coronary angiography. Scintigraphic images were blindly and independently evaluated by three observers. Coronary stenosis was defined as a >50% narrowing in luminal diameter; severe stenosis was defined as a proximal stenosis of >75% or a peripheral stenosis of >90%. Coronary angiography revealed normal coronary arteries or insignificant coronary stenosis in 13 patients and significant coronary stenoses in 67 patients. The sensitivity and specificity of 99mTc-tetrofosmin SPET in respect of severely stenosed vessels were, respectively, 80% and 65% for the left anterior descending artery (LAD), 100% and 46% for the right coronary artery (RCA) and 58 and 78% for the left circumflex artery (LCx) territories. Considering all the significantly stenosed vessels, a significant decrease in sensitivity was observed for LAD territories (to 59%, P=0.05), and a nonsignificant decrease for RCA (88%) and LCx (47%) territories while specificity values remained essentially unchanged. No significant changes in sensitivity or specificity were observed when regions with previous myocardial infarction were excluded. In conclusion, the sensitivity of 99mTc-tetrofosmin SPET for the localization of individual stenosed vessels is only moderate when all significant stenoses are considered, but the ability of this technique to predict the location of severe coronary artery stenoses seems satisfactory, with the exception of the low specificity in respect of RCA territories.

Intracoronary thrombi are a common finding in the setting of acute coronary syndromes and correlate with intraprocedural complications, adverse prognosis and unpredictable response to standard pharmacological and interventional treatment. Interventional cardiologists have learned to fear the so-called hostile thrombus, with its aggressive and unstable behavior often leading to abrupt and refractory vessel closure. Here we report a case series of intracoronary bivalirudin administration to treat massive intracoronary thrombi, leading to rapid clot disappearance and coronary blood flow restoration. Interventional cardiologists might consider intracoronary bivalirudin administration as a bailout strategy during unusual critical situations.

Biodegradable polymer drug eluting stents (BP-DES) have been developed to overcome the limitations of first generation durable polymer DES (DP-DES) but the clinical results of different BP-DES are not consistent. We performed a meta-analysis to compare the outcomes of BP-DES and DP-DES in the treatment of coronary artery disease (CAD).Online databases including MEDLINE were searched for studies comparing BP-DES and DP-DES for obstructive CAD that reported rates for overall mortality, myocardial infarction (MI), late stent thrombosis (LST), target lesion revascularization (TLR) and late lumen loss (LLL) with a follow-up of ≥ 6 months. Ten studies (5834 patients) with a 1-year median follow-up were included in the meta-analysis. When comparing patients treated with DP-DES and BP-DES those treated with BP-DES had lower LLL (in-stent: weighted mean difference (WMD) -0.10 mm, 95% CI = -0.17 to -0.03 mm, p = 0.004; in-segment: WMD -0.06 mm, 95% CI = -0.10 to -0.01 mm, p = 0.01) with lower TLR rates (OR 0.67, 95% CI = 0.47 to 0.98, p = 0.04). However, BP-DES did not improve mortality (OR 0.97, 95% CI = 0.73 to 1.29, p = 0.83), MI (OR 1.13, 95% CI = 0.87 to 1.46, p = 0.36) or LST rates (OR 0.64, 95% CI = 0.36 to 1.16, p = 0.14). A pre-specified subgroup analysis of Biolimus BP-DES confirmed significant LLL reduction without differences in other clinical endpoints. Meta-regression analysis demonstrated a strong significant inverse correlation between LLL and reference coronary diameter (p 0.001).Our present meta-analysis showed that BP-DES when compared with DP-DES significantly reduced LLL and TVR but without clear benefits on mortality, MI and LST rates. (Clinicaltrials.gov identifier: NCT01466634).

Yersinia enterocolitica is an unusual cause of septicaemia, usually occurring in immunocompromised hosts. Endocardial involvement is rare and generally presents as acute endocarditis. We describe the case of a 73-y-old woman, apparently without risk factors for endocarditis, admitted to hospital for persistent fever of unknown origin, arthralgia, and weight loss. Y. enterocolitica was isolated from blood and urine cultures, and echocardiography showed a pedunculated vegetation attached to the non-coronary cusp of the aortic valve. Symptoms and fever resolved after 3 days of intravenous cefotaxime plus amikacin, which were continued for the 2 weeks of her hospital stay; this treatment was followed by intravenous ceftriaxone after discharge. We hypothesized that a chemotherapy course administered 2 months previously for breast cancer might have been a predisposing factor for the Y. enterocolitica valvular infection and that immune system recovery contributed to mitigate the clinical presentation as subacute endocarditis.

Acute coronary syndromes and, in paticular, ST – segment elevation myocardial infarction are the principle causes or mortality and morbidity in the industrialized countries. The manadgement of acute myocadial infarction is much debated in the literature; primary percutaneous coronary intervention is the treatment of choice. In the recent years there has been an increasing interest in the concept of adjunctive pharmacological therapy to improve outcomes in primary percutaneous coronary intervention. In the literature randomized trials of intravenous or more recently intracoronary injection of glycoprotein IIb/IIIa inhibitors have provided conflicting results with no definitive evidence for efficacy. The aim of the report is to review the evidence to our date on the role of intracoronary injection of abciximab during primary percutaneous intervention in the setting of acute myocardial infarction.

Fibrinogen elevation is associated with a worse prognosis in patients with acute coronary syndrome (ACS). The aim of the present study was to assess the prognostic value of increased fibrinogen concentrations in ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI).A total of 428 STEMI patients treated with primary PCI were retrospectively selected (median age: 62 years; 82.5% males) from a continuous case series of 832 ACS patients. Plasma fibrinogen concentrations were measured before PCI and after 24, 48, and 72 hours. In the 4-year follow-up, one major adverse cardiovascular event (MACE) occurred in 111 patients (40%): 17 re-STEMI (7%), 64 re-PCI (22%), 22 cardiac deaths (7%), and eight non ST-elevated acute coronary syndromes (NSTEACS, 4%).According to the reference change value, fibrinogen concentrations increased in 25% of patients at 24 h, 64% at 48 h and 19% at 72 h. Only fibrinogen concentrations at 48 h showed a mild association with overall MACEs (p = 0.036): the risk increased, starting from a concentration of 4 g/L. However a further multivariate model did not confirm any prognostic value. No association with specific MACEs emerged.In contrast to NSTEACS patients, fibrinogen concentrations increased slightly in STEMI patients after primary PCI, however, they were not as prognostic as for MACEs.

Background: Third generation troponin assays should aid in the rule-out of acute myocardial infarction (AMI). The study aim was to assess the capability of admission measurement of ultra-sensitive troponin I (TnI-Ultra) to exclude AMI from other myocardial injury. Methods: The fi rst TnI-Ultra sample from 856 patients at presentation to the Emergency Department and subsequent admission to the Cardiac Care Unit were considered in this case series. Myoglobin was simultaneously detected in 684 patients. Results: The sensitivity of the fi rst single TnI-Ultra level was 82.5 % in overall AMI, and similar in ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarc-tion (NSTEMI), admitted, respectively at 3 and 8 h from symptoms. The diagnostic capability of a fi rst single TnI-Ultra level was poor for both STEMI and NSTEMI to dis-criminate and rule-out overall AMI from myocardial injury, with an area under the receiver-operating curve of 0.65 and a negative likelihood ratio of 0.55. Adopting an optimal test threshold or adding myoglobin detection did not improve TnI-Ultra performances. Conclusions: The capability of a fi rst single TnI-Ultra level to exclude AMI from other myocardial injury in early and late presenters is poor. Addition of myoglobin assay offered no further improvement and was not considered useful. Keywords: acute myocardial infarction; biomarkers; diagno-sis; sensitivity; troponin.

This study assesses the relative prognostic value of increased left ventricular (LV) mass compared with residual ischemic myocardium and angiographic characteristics of the diseased vessel in 76 patients with uncomplicated acute myocardial infarction associated with 1-vessel coronary artery disease (CAD). All patients underwent symptom-limited treadmill exercise testing, resting and dipyridamole echocardiography and coronary angiography before discharge, and were followed-up for 32 ± 6 months. LV measurements were obtained in diastole according to the Penn convention. Measurements of LV mass were divided by body surface area to obtain LV mass index. A cut-off value of 135 g/m2 body surface area for men and 112 g/m2 for women was prospectively selected. The individual effects of clinical, stress testing and anglographic variables were evaluated by using the Cox regression model. Echocardiographic LV mass index was increased in 43 patients and normal in 33. There was no intergroup difference with respect to baseline clinical and angiographic variables, ejection fraction and prevalence of stress-induced ischemia. During follow-up there were 23 cardiac events in the 43 patients with increased LV mass index and only 5 in the 33 with normal LV :Mass index (p

Background No information is available on the optimal sampling time to catch the highest increase for biomarkers whose elevation after ST-elevation myocardial infarction (STEMI) is prognostic for adverse events. This study aimed to investigate release kinetics and peak times of cardiac troponin I (cTnI), C-reactive protein (CRP), B-type natriuretic peptide (BNP), chromogranin A (CgA) and cystatin C (CyC) in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Methods Blood concentrations of cTnI, CRP, BNP, CgA and CyC were measured before and 6 h, 24 h, and 48 h after PPCI in 84 STEMI patients. The averaged trajectory of marker kinetics was estimated by multivariable regression models adjusted for patient characteristics and orthogonal polynomials were used to describe related releases. Results From the estimated kinetics cTnI peaked at 10 h from symptoms, BNP at 28 h and CRP within 30 h. CyC concentrations did not change, whereas CgA concentrations increased from 6 to 48 h after PPCI. The amount of BNP release was found to be affected by the interaction between gender and age: females Conclusions According to different release kinetics a single blood sampling for measuring all biomarkers is not recommended.

The association of variant angina (VA) and myocardial bridges is a rare finding. We describe a case of VA with recurrent coronary spasm triggered by different stimuli at the site of a myocardial bridge. The interplay of endothelial dysfunction, coronary vasoconstriction and myocardial bridging was detected by intracoronary acetylcholine test and IVUS. We speculate that mechanical stimulation at the bridge site caused endothelial dysfunction and enhanced local susceptibility to vasoconstrictor stimuli. Variant angina should always be suspected in cases of ST-elevation acute coronary syndrome without any significant angiographic coronary stenosis.

BACKGROUND Cystatin C (CC) has been proposed to play a role in atherosclerosis. We aimed to review the prognostic value of CC serum/plasma levels in patients with acute coronary syndromes (ACS). METHODS Fifteen observational longitudinal studies were selected by Medline. RESULTS Increased CC over threshold values ranging from 0.93 to 1.3 mg/L were prognostic for death (hazard ratio; HR: 2.04-3.6) and for the occurrence of any fatal and non-fatal cardiovascular events (HR: 1.7-9.6) for patients with either ACS only or coronary heart disease and prevalent ACS. Only one study showed an increased risk for future myocardial infarction (MI) in patients with marker levels higher than 1.0 mg/L. Three studies reported the risk associated with a change of one unit of CC for long-term death (HR ranging from 1.9 to 6.3) and for the composite end point of 1 year MI and death (HR 2.15). Some studies showed the additional prognostic value contributed from CC measurements to other markers and to conventional risk scores. CONCLUSION Despite low to moderate evidence, there is a general agreement on the significant prognostic value of CC in ACS that might encourage further research focused on risk assessment for patients with MI.

In a variant proportion of patients presenting with chest pain and electrocardiographic changes characteristic for ST – elevation myocardial infarction, percutaneous coronary intervention achieves epicardial coronary artery reperfusion but not the myocardial reperfusion (ranging from 5p to 50p). Furthermore, prolonged myocardial ischemia often breaks down the coronary microvasculature and the flow to the infarct myocardium may seem to be markedly reduced. This condition is known as no reflow – phenomenon. The no reflow - phenomenon is associated with an increased incidence of malignant ventricular arrhythmias, heart failure and 30-days mortality. In the recent years in literature, several articles (subsequently discussed in the present review) have been published and made relevant to the study of the pathophysiology regarding no reflow – phenomenon. This knowledge has assisted in the development of new treatment strategies, such as prophylactic use of vasodilators, mechanical devices and drugs inhibiting platelet. The review has focused on the current literature about intra – coronary injection of drugs to treat no – reflow and microvascular dysfunction.

Protein S is a vitamin K-dependent plasma protein involved in the regulation of the protein C anticoagulant pathway,1 the system responsible for the inactivation of factors Va and VIIIa2. Protein S functions as a cofactor for activated protein C by increasing its affinity for the cell surface3 and by blocking the capacity of factor Xa to protect factor Va from inactivation by activated protein C4; it also enhances the profibrinolytic effects of activated protein C5–7. The congenital deficiency of protein S is associated with an increased risk of recurrent juvenile venous and arterial thromboembolism8–10. . . .