IL-1 Receptor Antagonist Anakinra in the Treatment of COVID-19 Acute Respiratory Distress Syndrome: A Retrospective, Observational Study.

The IL-1 receptor antagonist, anakinra, may represent a therapeutic option for acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19). In this study, COVID-19 ARDS patients admitted to the Azienda Socio Sanitaria Territoriale of Lecco, Italy, between March 5th to April 15th, 2020, and who had received anakinra off-label were retrospectively evaluated and compared with a cohort of matched controls who did not receive immunomodulatory treatment. The primary end point was survival at day 28. The population consisted of 112 patients (56 treated with anakinra and 56 controls). Survival at day 28 was obtained in 69 patients (61.6%) and was significantly higher in anakinra-treated patients than in the controls (75.0 versus 48.2%, p = 0.007). When stratified by continuous positive airway pressure support at baseline, anakinra-treated patients' survival was also significant compared with the controls (p = 0.008). Univariate analysis identified anakinra usage (odds ratio, 3.2; 95% confidence interval, 1.47-7.17) as a significant survival predictor. This was not supported by multivariate modeling. The rate of infectious-related adverse events was similar between groups. In conclusion, anakinra improved overall survival and invasive ventilation-free survival and was well tolerated in patients with ARDS associated with COVID-19.

G-CSF for Extensive STEMI.

RATIONALE: In the exploratory Phase II STEM-AMI (Stem Cells Mobilization in Acute Myocardial Infarction) trial, we reported that early administration of G-CSF (granulocyte colony-stimulating factor), in patients with anterior ST-segment-elevation myocardial infarction and left ventricular (LV) dysfunction after successful percutaneous coronary intervention, had the potential to significantly attenuate LV adverse remodeling in the long-term. OBJECTIVE: The STEM-AMI OUTCOME CMR (Stem Cells Mobilization in Acute Myocardial Infarction Outcome Cardiac Magnetic Resonance) Substudy was adequately powered to evaluate, in a population showing LV ejection fraction ≤45% after percutaneous coronary intervention for extensive ST-segment-elevation myocardial infarction, the effects of early administration of G-CSF in terms of LV remodeling and function, infarct size assessed by late gadolinium enhancement, and myocardial strain. METHODS AND RESULTS: Within the Italian, multicenter, prospective, randomized, Phase III STEM-AMI OUTCOME trial, 161 ST-segment-elevation myocardial infarction patients were enrolled in the CMR Substudy and assigned to standard of care (SOC) plus G-CSF or SOC alone. In 119 patients (61 G-CSF and 58 SOC, respectively), CMR was available at baseline and 6-month follow-up. Paired imaging data were independently analyzed by 2 blinded experts in a core CMR lab. The 2 groups were similar for clinical characteristics, cardiovascular risk factors, and pharmacological treatment, except for a trend towards a larger infarct size and longer symptom-to-balloon time in G-CSF patients. ANCOVA showed that the improvement of LV ejection fraction from baseline to 6 months was 5.1% higher in G-CSF patients versus SOC (P=0.01); concurrently, there was a significant between-group difference of 6.7 mL/m2 in the change of indexed LV end-systolic volume in favor of G-CSF group (P=0.02). Indexed late gadolinium enhancement significantly decreased in G-CSF group only (P=0.04). Moreover, over time improvement of global longitudinal strain was 2.4% higher in G-CSF patients versus SOC (P=0.04). Global circumferential strain significantly improved in G-CSF group only (P=0.006). CONCLUSIONS: Early administration of G-CSF exerted a beneficial effect on top of SOC in patients with LV dysfunction after extensive ST-segment-elevation myocardial infarction in terms of global systolic function, adverse remodeling, scar size, and myocardial strain. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01969890.

A randomized trial of colchicine for acute pericarditis.

BACKGROUND: Colchicine is effective for the treatment of recurrent pericarditis. However, conclusive data are lacking regarding the use of colchicine during a first attack of acute pericarditis and in the prevention of recurrent symptoms. METHODS: In a multicenter, double-blind trial, eligible adults with acute pericarditis were randomly assigned to receive either colchicine (at a dose of 0.5 mg twice daily for 3 months for patients weighing >70 kg or 0.5 mg once daily for patients weighing ≤70 kg) or placebo in addition to conventional antiinflammatory therapy with aspirin or ibuprofen. The primary study outcome was incessant or recurrent pericarditis. RESULTS: A total of 240 patients were enrolled, and 120 were randomly assigned to each of the two study groups. The primary outcome occurred in 20 patients (16.7%) in the colchicine group and 45 patients (37.5%) in the placebo group (relative risk reduction in the colchicine group, 0.56; 95% confidence interval, 0.30 to 0.72; number needed to treat, 4; P<0.001). Colchicine reduced the rate of symptom persistence at 72 hours (19.2% vs. 40.0%, P=0.001), the number of recurrences per patient (0.21 vs. 0.52, P=0.001), and the hospitalization rate (5.0% vs. 14.2%, P=0.02). Colchicine also improved the remission rate at 1 week (85.0% vs. 58.3%, P<0.001). Overall adverse effects and rates of study-drug discontinuation were similar in the two study groups. No serious adverse events were observed. CONCLUSIONS: In patients with acute pericarditis, colchicine, when added to conventional antiinflammatory therapy, significantly reduced the rate of incessant or recurrent pericarditis. (Funded by former Azienda Sanitaria Locale 3 of Turin [now Azienda Sanitaria Locale 2] and Acarpia; ICAP ClinicalTrials.gov number, NCT00128453.).

Granulocyte-colony stimulating factor for large anterior ST-elevation myocardial infarction: rationale and design of the prospective randomized phase III STEM-AMI OUTCOME trial.

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) has been clinically tested in ST-elevation myocardial infarction (STEMI) with mixed results. Our 3-year follow-up data from STEM-AMI trial documented a sustained benefit of G-CSF on adverse ventricular remodeling after large anterior STEMI, when administered early and at a high-dose in patients with left ventricular (LV) dysfunction. The Aim of the present trial is to establish whether G-CSF improves hard clinical long-term outcomes. METHODS: The STEM-AMI OUTCOME is a prospective, multicenter, randomized, open-label, phase III trial. It will include 1,530 patients with anterior STEMI undergoing primary percutaneous coronary intervention 2 to 24 hours after symptoms onset and with LV ejection fraction ≤45% after successful reperfusion. Patients will be randomized 1:1 to G-CSF and/or standard treatment. The primary end point is a reduced occurrence of all-cause death, recurrence of myocardial infarction, or hospitalization due to heart failure in G-CSF-treated patients. Left ventricular remodeling will be assessed via cardiac ultrasound and a substudy with cardiac magnetic resonance will be carried out in 120 subjects. Accrual and follow-up periods will last 3 and 2 years, respectively. CONCLUSIONS: The STEM-AMI OUTCOME study is designed to be a rigorous controlled phase III trial with adequate statistical power to conclusively assess efficacy of G-CSF treatment in STEMI.

A case of atrial tachycardia treated with ivabradine as bridge to ablation.

Ivabradine is indicated in cardiac failure and ischemia to reduce sinus rate by inhibition of the pacemaker I(f) current in sinoatrial node. We report a case of an 18-year-old woman with left atrial tachyarrhythmia resistant to several antiarrhythmic drugs and to electric cardioversion who responded only to ivabradine, which significantly reduced heart rate without abolishing the arrhythmia itself. An ectopic focus in the ostium of left pulmonary veins was found and the patient was successfully ablated. We suggest that ivabradine might be therefore useful in the treatment of supraventricular tachyarrhythmias due to an enhanced automaticity.

Granulocyte colony-stimulating factor for stem cell mobilisation in acute myocardial infarction: a randomised controlled trial.

BACKGROUND: To determine whether granulocyte colony-stimulating factor (G-CSF) improves clinical outcomes after large ST-elevation myocardial infarction (STEMI) when administered early in patients with left ventricular (LV) dysfunction after successful percutaneous coronary intervention (PCI). METHODS: STEM-AMI OUTCOME was designed as a prospective, multicentre, nationwide, randomised, open-label, phase III trial (ClinicalTrials.gov ID: NCT01969890) to demonstrate the efficacy and safety of early G-CSF administration in reducing 2-year cardiac mortality and morbidity in patients with STEMI with LV ejection fraction ≤45% after PCI. The primary outcome was a composite of all-cause death, recurrence of myocardial infarction and hospitalisation for heart failure. Due to low recruitment and event rates, the study was discontinued and did not achieve adequate statistical power to verify the hypothesis. RESULTS: Patients were randomly allocated to G-CSF (n=260) or standard of care (SOC; n=261). No difference was found in the composite primary outcome between study groups (HR 1.20; 95% CI 0.63 to 2.28). The 2-year mortality was 2.31% in the G-CSF and 2.68% in the control group (HR 0.88; 95% CI 0.29 to 2.60). Adverse events did not differ between the G-CSF (n=65) and SOC groups (n=58; OR 1.17; 95% CI 0.78 to 1.75). In post hoc analyses on the intervention group, we observed a trend towards fewer composite primary outcomes in patients with low bone marrow (BM) cell mobilisation (n=108) versus those with high mobilisation (n=152, with peak leucocyte count >50×109/L; HR 2.86; 95% CI 0.96 to 8.56). Primary outcomes were lower in patients with severe LV systolic dysfunction at discharge treated with G-CSF than in controls (interaction ß±SE, -0.08±0.04; p=0.034). CONCLUSIONS: Although inconclusive, this is the largest trial in the field of cell-based cardiac repair after STEMI providing evidence of the tolerability and long-term safety of G-CSF treatment. The results prompt further studies to understand which patient can benefit most from BM cell mobilisation. TRIAL REGISTRATION NUMBER: NCT01969890.

Recurrent pericarditis in older adults: Clinical and laboratory features and outcome.

BACKGROUND: Current guidelines for the diagnosis and treatment of pericarditis refer to the general adult population. Few and fragmentary data regarding recurrent pericarditis in older adults exist. OBJECTIVE OF THE STUDY: Given the absence of specific data in scientific literature, we hypothesized that there might be clinical, laboratory and outcome differences between young adults and older adults affected by idiopathic recurrent pericarditis. MATERIALS AND METHODS: We performed an international multicentric retrospective cohort study analyzing data from patients affected by recurrent pericarditis (idiopathic or post-cardiac injury) and referring to tertiary referral centers. Clinical, laboratory, and outcome data were compared between patients younger than 65 years (controls) and patients aged 65 or older. RESULTS: One hundred and thirty-three older adults and 142 young adult controls were enrolled. Comorbidities, including chronic kidney diseases, atrial fibrillation, and diabetes, were more present in older adults. The presenting symptom was dyspnea in 54.1% of the older adults versus 10.6% in controls (p < 0.001); pain in 32.3% of the older adults versus 80.3% of the controls (p < 0.001). Fever higher than 38°C was present in 33.8% versus 53.5% (p = 0.001). Pleural effusion was more prevalent in the older adults (55.6% vs 34.5%, p < 0.001), as well as severe pericardial effusion (>20 mm) (24.1% vs 12.7%, p = 0.016) and pericardiocentesis (16.5% vs 8.5%, p = 0.042). Blood leukocyte counts were significantly lower in the older adults (mean + SE: 10,227 + 289/mm3 vs 11,208 + 285/mm3, p = 0.016). Concerning therapies, NSAIDS were used in 63.9% of the older adults versus 80.3% in the younger (p = 0.003), colchicine in 76.7% versus 87.3% (p = 0.023), corticosteroids in 49.6% versus 26.8% (p < 0.001), and anakinra in 14.3% versus 23.9% (p = 0.044). CONCLUSIONS: Older adults affected by recurrent pericarditis show a different clinical pattern, with more frequent dyspnea, pleural effusion, severe pericardial effusion, and lower fever and lower leukocyte count, making the diagnosis sometimes challenging. They received significantly less NSAIDs and colchicine, likely due to comorbidities; they were also treated less commonly with anti-IL1 agents, and more frequently with corticosteroids.

Gastrointestinal bleeding associated to aortic valve stenosis (Heyde's syndrome): a case series and literature review.

Background: The association among aortic valve stenosis, gastrointestinal bleeding, and anaemia due to arteriovenous malformations, known as Heyde's syndrome (HS), is poorly understood and controversial. Recently, acquired Type 2A von Willebrand syndrome (vWS 2A) was shown to be the most likely aetiological mechanism of anaemia. Case summary: We report two cases of HS in whom the percutaneous replacement of the aortic valve was resolutive for iron deficiency anaemia. Discussion: Iron deficiency anaemia and aortic stenosis are a common association in the elderly, so much that frequently; in such cases, the correction of the valvulopathy is often excluded as pre-operative anaemia is associated with higher morbidity and mortality. From this perspective, the correct diagnosis of HS is crucial to guide the decision to correct valvulopathy, as valvular substitution is resolutive for both anaemic disorders and aortic stenosis.

Circulating microRNAs are new and sensitive biomarkers of myocardial infarction.

AIMS: Circulating microRNAs (miRNAs) may represent a novel class of biomarkers; therefore, we examined whether acute myocardial infarction (MI) modulates miRNAs plasma levels in humans and mice. METHODS AND RESULTS: Healthy donors (n = 17) and patients (n = 33) with acute ST-segment elevation MI (STEMI) were evaluated. In one cohort (n = 25), the first plasma sample was obtained 517 ± 309 min after the onset of MI symptoms and after coronary reperfusion with percutaneous coronary intervention (PCI); miR-1, -133a, -133b, and -499-5p were ~15- to 140-fold control, whereas miR-122 and -375 were ~87-90% lower than control; 5 days later, miR-1, -133a, -133b, -499-5p, and -375 were back to baseline, whereas miR-122 remained lower than control through Day 30. In additional patients (n = 8; four treated with thrombolysis and four with PCI), miRNAs and troponin I (TnI) were quantified simultaneously starting 156 ± 72 min after the onset of symptoms and at different times thereafter. Peak miR-1, -133a, and -133b expression and TnI level occurred at a similar time, whereas miR-499-5p exhibited a slower time course. In mice, miRNAs plasma levels and TnI were measured 15 min after coronary ligation and at different times thereafter. The behaviour of miR-1, -133a, -133b, and -499-5p was similar to STEMI patients; further, reciprocal changes in the expression levels of these miRNAs were found in cardiac tissue 3-6 h after coronary ligation. In contrast, miR-122 and -375 exhibited minor changes and no significant modulation. In mice with acute hind-limb ischaemia, there was no increase in the plasma level of the above miRNAs. CONCLUSION: Acute MI up-regulated miR-1, -133a, -133b, and -499-5p plasma levels, both in humans and mice, whereas miR-122 and -375 were lower than control only in STEMI patients. These miRNAs represent novel biomarkers of cardiac damage.

Impact of clinical and subclinical coronary artery disease as assessed by coronary artery calcium in COVID-19.

BACKGROUND AND AIMS: The potential impact of coronary atherosclerosis, as detected by coronary artery calcium, on clinical outcomes in COVID-19 patients remains unsettled. We aimed to evaluate the prognostic impact of clinical and subclinical coronary artery disease (CAD), as assessed by coronary artery calcium score (CAC), in a large, unselected population of hospitalized COVID-19 patients undergoing non-gated chest computed tomography (CT) for clinical practice. METHODS: SARS-CoV 2 positive patients from the multicenter (16 Italian hospitals), retrospective observational SCORE COVID-19 (calcium score for COVID-19 Risk Evaluation) registry were stratified in three groups: (a) "clinical CAD" (prior revascularization history), (b) "subclinical CAD" (CAC >0), (c) "No CAD" (CAC = 0). Primary endpoint was in-hospital mortality and the secondary endpoint was a composite of myocardial infarction and cerebrovascular accident (MI/CVA). RESULTS: Amongst 1625 patients (male 67.2%, median age 69 [interquartile range 58-77] years), 31%, 57.8% and 11.1% had no, subclinical and clinical CAD, respectively. Increasing rates of in-hospital mortality (11.3% vs. 27.3% vs. 39.8%, p < 0.001) and MI/CVA events (2.3% vs. 3.8% vs. 11.9%, p < 0.001) were observed for patients with no CAD vs. subclinical CAD vs clinical CAD, respectively. The association with in-hospital mortality was independent of in-study outcome predictors (age, peripheral artery disease, active cancer, hemoglobin, C-reactive protein, LDH, aerated lung volume): subclinical CAD vs. No CAD: adjusted hazard ratio (adj-HR) 2.86 (95% confidence interval [CI] 1.14-7.17, p=0.025); clinical CAD vs. No CAD: adj-HR 3.74 (95% CI 1.21-11.60, p=0.022). Among patients with subclinical CAD, increasing CAC burden was associated with higher rates of in-hospital mortality (20.5% vs. 27.9% vs. 38.7% for patients with CAC score thresholds≤100, 101-400 and > 400, respectively, p < 0.001). The adj-HR per 50 points increase in CAC score 1.007 (95%CI 1.001-1.013, p=0.016). Cardiovascular risk factors were not independent predictors of in-hospital mortality when CAD presence and extent were taken into account. CONCLUSIONS: The presence and extent of CAD are associated with in-hospital mortality and MI/CVA among hospitalized patients with COVID-19 disease and they appear to be a better prognostic gauge as compared to a clinical cardiovascular risk assessment.

Unusual case of myocardial injury induced by Escherichia coli sepsis.

The typical symptoms and signs of myocardial infarction are well known. Alterations in electrocardiogram (ECG), echocardiography or biochemical markers of myocardial necrosis are usually helpful to confirm the diagnosis. Some of these features, however, also occur in myocarditis, which is a potential differential diagnosis. We describe an unusual case of bacterial sepsis due to Escherichia coli that caused myocardial damage (myocarditis) with ECG changes mimicking acute myocardial infarction. The possible pathophysiological mechanisms of myocardial injury in sepsis are also reviewed.

Outcomes of idiopathic chronic large pericardial effusion.

OBJECTIVE: Aim of this paper is to evaluate the outcomes of 'idiopathic' chronic large pericardial effusions without initial evidence of pericarditis. METHODS: All consecutive cases of idiopathic chronic large pericardial effusions evaluated from 2000 to 2015 in three Italian tertiary referral centres for pericardial diseases were enrolled in a prospective cohort study. The term 'idiopathic' was applied to cases that performed a complete diagnostic evaluation to exclude a specific aetiology. A clinical and echocardiographic follow-up was performed every 3-6 months. RESULTS: 100 patients were included (mean age 61.3±14.6 years, 54 females, 44 patients were asymptomatic according to clinical evaluation) with a mean follow-up of 50 months. The baseline median size of the effusion (evaluated as the largest end-diastolic echo-free space) was 25 mm (IQR 8) and decreased to a mean value of 7 mm (IQR 19; p<0.0001) with complete regression in 39 patients at the end of follow-up. There were no new aetiological diagnoses. Adverse events were respectively: cardiac tamponade in 8 patients (8.0%), pericardiocentesis in 30 patients (30.0%), pericardial window in 12 cases (12.0%) and pericardiectomy in 3 patients (3.0%). Recurrence-free survival and complications-free survival was better in patients treated without interventions (log rank p=0.0038). CONCLUSIONS: The evolution of 'idiopathic' chronic large pericardial effusions is usually benign with reduction of the size of the effusion in the majority of cases, and regression in about 40% of cases. The risk of cardiac tamponade is 2.2%/year and recurrence/complications survival was better in patients treated conservatively without interventions.

Evolution of the pericardiocentesis technique.

: Pericardiocentesis is a valuable technique for the diagnosis and treatment of patients with pericardial effusion and cardiac tamponade, although it may be associated with potentially serious complications. Through the years, many different imaging approaches have been described to reduce the complication rate of the procedure. This systematic review provides a focused overview of the different techniques developed in recent years to reduce the procedural complications and to increase the related success rate.

[Cardiac infection by Listeria monocytogenes]. / Infezione cardiaca da Listeria monocytogenes.

We report the case of a 56-year-old man showing numerous cardiovascular manifestations of Listeria infection (myo-pericarditis, coronary vasospasm, intracavitary vegetations/thrombus, sinoatrial blocks). Cardiac magnetic resonance and echocardiography images provided an unexpected picture of this infection, and were relevant for the appropriate clinical management. Transthoracic and transesophageal echocardiography were useful for assessing the presence of an endocavitary mass. Tissue characterization by cardiac magnetic resonance confirmed the presence of a thrombus and revealed signs of active inflammation in the myocardial wall, pericardium and vascular pedicle.

Twelve-month outcome of patients with an established indication for oral anticoagulation undergoing coronary artery stenting and stratified by the baseline risk of bleeding: Insights from the Warfarin and Coronary Stenting (War-Stent) Registry.

PURPOSE: To evaluate the outcome of patients with an established indication for oral anticoagulation (OAC) undergoing coronary stent implantation (PCI-S) and stratified by the baseline risk of bleeding. MATERIAL AND METHODS: The database of the prospective, multicentre, observational WAR-STENT registry (ClinicalTrials.gov identifier NCT00722319) was analyzed and patients with atrial fibrillation and CHA2DS2-VASc score ≥2, mechanical heart valve, prior cardiac embolism, intra-cardiac thrombus and recent venous thromboembolism who were treated with either triple (warfarin, aspirin and clopidogrel) or dual (warfarin and clopidogrel) or dual antiplatelet (aspirin and clopidogrel) therapy, identified. Patients were then sorted into two groups at non-low and low risk of bleeding, as defined by an ATRIA score >3 and ≤3 respectively, and compared regarding major adverse cardiac and vascular events (MACVE) and bleeding. RESULTS: At 12-month follow up, MACVE were comparable in the two groups, whereas total, major and minor bleeding, as well as combined MACVE and total bleeding, were significantly more frequent in the non-low bleeding risk group. Upon Cox univariate and multivariable analysis, non-low bleeding risk category confirmed as an independent predictor of major bleeding. The choice of antithrombotic therapy however, appeared not to be influenced by the bleeding risk category at baseline. CONCLUSIONS: In patients with an established indication for OAC undergoing PCI-S, non-low bleeding risk category is the most potent independent predictor of major bleeding. Stratification of the bleeding risk at baseline should therefore be regarded as an indispensable process to be carried out before selection of the antithrombotic therapy.

Safety, Efficacy, and Complications of Pericardiocentesis by Real-Time Echo-Monitored Procedure.

Pericardiocentesis is useful in the diagnosis and treatment of pericardial effusive disease. To date, a number of methods have been developed to reduce complications and increase the success rate of the procedure. The aim of the present study was to evaluate the efficacy and the safety of echocardiography-guided pericardiocentesis under continuous echocardiographic monitoring in the management of pericardial effusion. We prospectively performed 161 pericardiocentesis procedures in 141 patients admitted from 1993 to 2015 in 3 centers. This procedure was performed for tamponade or large pericardial effusion in 157 cases and for diagnosis in 4 cases. A percutaneous puncture was performed where the largest amount of fluid was detected. To perform a real-time echo-guided procedure, a multi-angle bracket was mounted on the echocardiographic probe to support the needle and enable its continuous visualization during the puncture. The procedure was successful in 160 of 161 cases (99%). Two major complications occurred (1.2%): 1 mediastinal hematoma that required surgical drainage in a patient on anticoagulant therapy and 1 pleuropericardial shunt requiring thoracentesis. Seven minor complications occurred (4.3%): 1 pleuropericardial shunt, 1 case of transient AV type III block, 3 vasovagal reactions (1 with syncope), and 2 cases of acute pulmonary edema managed with medical therapy. No punctures of any cardiac chamber occurred, and emergency surgical drainage was not required in any case. In conclusion, echocardiography-guided pericardiocentesis under continuous visualization is effective, safe, and easy to perform, even in hospitals with low volumes of procedures with or without cardiac surgery.

The role of early contrast-enhanced chest computed tomography in the aetiological diagnosis of patients presenting with cardiac tamponade or large pericardial effusion.

AIMS: The role of chest computed tomography (CT) is not well defined for either diagnosis or management of pericardial disease. The aim of this study was to evaluate the added value of early chest CT in the diagnostic workup for patients presenting with cardiac tamponade or large pericardial effusion of unknown aetiology as the first manifestation of disease. METHODS AND RESULTS: We performed CT scan on 55 patients with pericardial effusion as defined above, undergoing echo-guided pericardiocentesis. We compared the success rate in making diagnosis and/or staging the underlying disorder of three sequential workups, including, respectively, (i) clinical presentation, inflammatory markers, chest X-ray imaging, (ii) all of the above and pericardial fluid analysis, and (iii) all of the above and chest CT. We were able to make diagnosis in 53 patients (96%): the major cause of effusion was malignancy (38%). Clinical and biochemical data were not able to differentiate non-tumour from tumour patients. CT revealed pathological findings in all patients with malignancy: tumour mass in 15/21 (71%) and pathological lymphadenopathy in the remaining 6 cases. The workup including CT provided a significantly higher diagnostic yield than the other two workups (P < 0.0001), both in the overall population and in the two subgroups of neoplastic (Npl) and non-Npl patients. CONCLUSION: In all patients with cardiac tamponade or large pericardial effusion, CT was useful either in identifying the underlying disease or in excluding other potential causes of pericardial effusion. We conclude that chest CT is a very useful non-invasive diagnostic tool to identify and stage pericardial diseases.

G-CSF treatment for STEMI: final 3-year follow-up of the randomised placebo-controlled STEM-AMI trial.

OBJECTIVE: To assess whether granulocyte colony-stimulating factor (G-CSF) treatment induces a sustained benefit on adverse remodelling in patients with large anterior ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction after successful reperfusion. METHODS: The STEM-AMI Trial was a prospective, placebo-controlled, multicentre study. Sixty consecutive patients with a first anterior STEMI, who underwent primary percutaneous coronary intervention 2-12 h after symptom onset, with LV ejection fraction (LVEF) ≤45% measured by echocardiography within 12 h after successful revascularisation (TIMI flow score ≥2), were randomised 1:1 to G-CSF (5 µg/Kg body weight b.i.d.) or placebo. Clinical events and Major Adverse Cardiac and Cerebrovascular Event (MACCE) were monitored, and LVEF, LV end-diastolic (LVEDV) and end-systolic (LVESV) volumes, and infarct size were evaluated by MRI at the final 3-year follow-up. RESULTS: Fifty-four patients completed the study, of whom 35 with MRI. No significant differences were found in mortality and MACCE between G-CSF and placebo-treated groups. The 3-year infarct size was not different between groups, whereas LVEDV was significantly lower in G-CSF (n=20) than in placebo (n=15) patients (170.1±8.1 vs 197.2±8.9 mL, respectively; p=0.033 at analysis of covariance). A significant inverse correlation was detected in G-CSF patients between the number of circulating CD34 cells at 30 days after reperfusion and the 3-year absolute and indexed LVEDV (ρ=-0.71, 95% CI -0.90 to -0.30, and ρ=-0.62, -0.86 to -0.14, respectively), or their change over time (r=-0.59, -0.85 to -0.11, and r=-0.55, -0.83 to -0.06, respectively). CONCLUSIONS: G-CSF therapy may be beneficial in attenuating ventricular remodelling subsequent to a large anterior STEMI in the long term. No differences have been detected in clinical outcome.

Diagnostic potential of plasmatic MicroRNA signatures in stable and unstable angina.

PURPOSE: We examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable (SA) and Unstable (UA) angina. METHODS: An exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated. RESULTS: Out of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA. CONCLUSIONS: This work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients.