Cesare Greco

Epidemiology of acute myocardial infarction in the Italian CCU network: the BLITZ study.

AIMS A large number of descriptive data on patients with acute myocardial infarction are based on clinical trials and registries on non consecutive patients: these data may give only a partial picture on treatment delay, patient characteristics, treatment and outcome of acute myocardial infarction in the real world. METHODS AND RESULTS The BLITZ survey prospectively enrolled all of the patients with acute myocardial infarction admitted in 296 (87%) Italian Coronary Care Units from 15-29 October 2001. Data on treatment delay, therapeutic strategies, duration of hospitalization and 30-day outcome were collected. One thousand nine hundred and fifty-nine consecutive patients (mean age 67+/-12 years, 70% males) were enrolled, 65% with ST-segment elevation (STEMI), 30% with no ST-segment elevation (NSTEMI) and 5% with undetermined ECG. The median delay between symptom onset and hospital arrival was 2h and 9 min with 76% of patients hospitalized within the sixth hour (26% within the first hour, 48% within the second). The median delay from hospital arrival to reperfusion therapy in STEMI was 45 min (IQR 26-85) for thrombolysis (50% of the patients) and 85 min (IQR 60-135) for primary angioplasty (15% of the patients). Coronary angiography was performed during hospital stay in 46% of the patients (STEMI 48%, NSTEMI 43%, undetermined AMI 35%), coronary angioplasty in 25% (STEMI 26%, NSTEMI 15%, undetermined AMI 13%) and coronary bypass in 1.4% (1%, 2.2% and 1% respectively). Twenty-two percent of the patients admitted to hospitals without cath-lab were transferred to a tertiary care hospital for invasive procedures. The overall median hospital stay was 10 days (IQR 7-12, STEMI 10, NSTEMI 9, undetermined AMI 11) and was not significantly different between hospitals with or without cath-lab (respectively, 9 and 10 days, P=0.38). After discharge and up to 30 days, coronary angiography was performed in 11% (STEMI 11%, NSTEMI 11%, undetermined MI 9%), angioplasty in 10% (STEMI 10%, NSTEMI 11%, undetermined MI 7%), bypass surgery in 7% (STEMI 5%, NSTEMI 11%, undetermined AMI 7%). The in-hospital and 30-day case fatality rates were 7.4% and 9.4%, respectively (7.5% and 9.5% for STEMI, 5.2% and 7.1% for NSTEMI, 18.2% and 21.2% for undetermined MI). CONCLUSIONS Patients with acute myocardial infarction admitted to the Italian CCUs, are older than those represented in clinical trials. A high proportion of these cases has the chance to receive early reperfusion therapy. Short-term mortality is lower than expected for patients with STEMI, but higher than reported for NSTEMI.

Angioplasty increases coronary sinus F2-isoprostane formation: evidence for in vivo oxidative stress during PTCA

OBJECTIVES Isoprostanes, stable end-products of oxygen free radical mediated-lipid peroxidation, were measured in the coronary vessels during percutaneous transluminal coronary angioplasty (PTCA) to provide direct evidence for enhanced oxidative stress in a local milieu in vivo. BACKGROUND Percutaneous transluminal coronary angioplasty is associated with complications such as myocardial stunning and accelerated restenosis, which at least in part are mediated by oxygen free radicals. Because isoprostanes are markers of oxidant stress and potent vasoactive compounds, the formation of which is not inhibited by aspirin treatment in vivo, it is possible that these mediators are increased locally during PTCA. METHODS In 12 coronary artery disease patients who were given aspirin and ticlopidine, blood samples from coronary sinus were taken immediately before and immediately upon balloon deflation during PTCA. Isoprostane F2alpha-III, isoprostane F2alpha-VI, and TxB2 were quantified after extraction and chromatography using a stable dilution isotope gas chromatography/mass spectrometry assay. RESULTS Coronary sinus and left main coronary artery levels of iPF2alpha-III and iPF2alpha-VI at baseline were (mean +/- SEM) 40 +/- 9 pg/ml and 115 +/- 10 pg/ml, respectively. The TxB2 levels were undetectable. Following PTCA, isoprostane levels markedly increased (mean +/- SEM): iPF2alpha-III, 125 +/- 12 pg/ml (p < 0.001); iPF2alpha-VI, 295 +/- 20 pg/ml (p < 0.001), whereas TxB2 levels remained undetectable. CONCLUSIONS These results indicate that PTCA induces coronary sinus increase in F2-isoprostane formation, and they also provide direct evidence for enhanced oxidative stress in a local milieu in vivo. Thus, an increased F2-isoprostane formation could play a role in the pathogenesis of some PTCA-associated untoward events.

Arterial access-site-related outcomes of patients undergoing invasive coronary procedures for acute coronary syndromes (from the ComPaRison of Early Invasive and Conservative Treatment in Patients With Non-ST-ElevatiOn Acute Coronary Syndromes [PRESTO-ACS] Vascular Substudy).

Transradial access (TRA) decreased bleeding after coronary interventions compared with femoral access (FA). However, no large study focused on arterial access-related outcomes in patients with acute coronary syndromes, although procedure-related bleeding significantly impaired prognosis. The aim was to evaluate access site-related outcomes of patients who underwent an invasive coronary procedure in the PRESTO-ACS Study. The cumulative primary study end point was death or reinfarction during hospitalization and at 1-year follow-up. Secondary end points were in-hospital bleeding and a net clinical outcome (combination of the primary end point and bleeding). Of 1,170 patients studied, 863 underwent a percutaneous coronary procedure using FA, and 307, using TRA. Compared with FA, TRA was associated with higher glycoprotein IIb/IIIa inhibitor use (52% vs 34%; p <0.0001). The in-hospital primary end point was similar between TRA (2.6%) and FA (2.9%; p = 0.79). However, TRA was associated with a significant decrease in bleeding (0.7% vs 2.4%; p = 0.05) and a nonsignificant decrease in net clinical outcome (3.3% vs 4.6%; p = 0.30). At 1-year follow-up, the TRA group had a statistically significant decrease in death or reinfarction (4.9% vs 8.3%; p = 0.05), bleeding (0.7% vs 2.7%; p = 0.03), and net clinical outcome (5.5% vs 9.9%; p = 0.02). In conclusion, in patients with non-ST-elevation acute coronary syndromes, use of TRA was associated with lower bleeding complications and identified patients with better long-term outcomes.

Comorbidities Frequency in Takotsubo Syndrome: An International Collaborative Systematic Review Including 1109 Patients

BACKGROUND To identify predisposing factors that can result in the onset of takotsubo syndrome, we performed an international, collaborative systematic review focusing on clinical characteristics and comorbidities of patients with takotsubo syndrome. METHODS We searched and reviewed cited references up to August 2013 to identify relevant studies. Corresponding authors of selected studies were contacted and asked to provide additional quantitative details. Data from each study were extracted by 2 independent reviewers. The cumulative prevalence of presenting features and comorbidities was assessed. Nineteen studies whose authors sent the requested information were included in the systematic review, with a total of 1109 patients (951 women; mean age, 59-76 years). Evaluation of risk factors showed that obesity was present in 17% of patients (range, 2%-48%), hypertension in 54% (range, 27%-83%), dyslipidemia in 32% (range, 7%-59%), diabetes in 17% (range, 4%-34%), and smoking in 22% (range, 6%-49%). Emotional stressors preceded takotsubo syndrome in 39% of patients and physical stressors in 35%. The most common comorbidities were psychological disorders (24%; range, 0-49%), pulmonary diseases (15%; range, 0-22%), and malignancies (10%; range, 4%-29%). Other common associated disorders were neurologic diseases (7%; range, 0-22%), chronic kidney disease (7%; range, 2%-27%), and thyroid diseases (6%; range, 0-37%). CONCLUSIONS Patients with takotsubo syndrome have a relevant prevalence of cardiovascular risk factors and associated comorbidities. Such of associations needs to be evaluated in further studies.

Real-world outcome of coronary bifurcation lesions in the drug-eluting stent era: Results from the 4,314-patient Italian Society of Invasive Cardiology (SICI-GISE) Italian Multicenter Registry on Bifurcations (I-BIGIS)

BACKGROUND Drug-eluting stents (DESs) introduction has somewhat renewed the issues of strategy and stenting technique for treatment of bifurcation lesions. In particular, concerns remain on extensive use of DESs, especially in the side branch, and on time of dual antiplatelet therapy (DAT) discontinuation, reflecting lack of pertinent long-term data. This study aimed to evaluate clinical safety and efficacy of different strategies for bifurcations treatment in a large observational real-world registry. METHODS A multicenter, retrospective Italian study of consecutive patients undergoing bifurcation percutaneous coronary intervention between January 2002 and December 2006 was performed. The primary end point was the long-term rate of major adverse cardiac events (MACEs). The role of DAT length on outcome was also analyzed. RESULTS A total of 4,314 patients (4,487 lesions) were enrolled at 22 independent centers. In-hospital procedural success rate was 98.7%. After median follow-up of 24 months, MACEs occurred in 17.7%, with cardiac death in 3.4%, myocardial infarction in 4.0%, target lesion revascularization in 13.2%, and stent thrombosis in 2.9%. Extensive multivariable analysis showed that MACEs were independently predicted by age, diabetes, renal failure, systolic dysfunction, multivessel disease, myocardial infarction at admission, restenotic lesion, bare-metal stent implantation, complex stenting strategy, and short duration of DAT. CONCLUSIONS This large study based on current clinical practice in an unselected patient population presenting with bifurcation disease and submitted to percutaneous coronary intervention demonstrated favorable long-term clinical results in this challenging patient setting, especially when DESs, simple stenting strategy, and DAT for at least 6 months are used.

Effectiveness of Two-Year Clopidogrel Aspirin in Abolishing the Risk of Very Late Thrombosis After Drug-Eluting Stent Implantation (from the TYCOON (Two-Year ClOpidOgrel Need) Study)

It remains unclear whether dual antiplatelet therapy >12 months might carry a better prognosis after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). To address the hypothesis that in the real world the risk of very late thrombosis after PCI with DESs can be decreased by an extended use of clopidogrel, we set up the Two-Year ClOpidOgrel Need (TYCOON) registry and prospectively investigated the impact on very late thrombosis of 12- versus 24-month dual antiplatelet regimens in an unselected population. The registry enrolled 897 consecutive patients who underwent PCI with stenting from January 1, 2003, to December 31, 2004, and had dual antiplatelet therapy. All patients had a 4-year clinical follow-up. In the 447 patients with DES implantation, the dual antiplatelet regimen after PCI was given for 12 months in the 173 patients treated in 2003 (12-month group) and for 24 months in the 274 patients treated in 2004 (24-month group). Comparison between groups did not reveal any significant difference in baseline clinical characteristics, angiographic and procedural features, and major adverse cardiac events. During follow-up, there were 5 cases of stent thrombosis after PCI in the 12-month DES group and 1 case in the 24-month DES group (p = 0.02). Specifically, there were 2 cases of subacute thrombosis (1 in each group), no case of late thrombosis, and 4 cases of very late thrombosis occurring at 13, 15, 17, and 23 months after DES implantation in the 12-month group only. In conclusion, a 2-year dual antiplatelet regimen with aspirin and clopidogrel can prevent the occurrence of very late stent thrombosis after PCI with DESs.

A pilot randomized study of ranolazine for reduction of myocardial damage during elective percutaneous coronary intervention

BACKGROUND Ranolazine is a new antianginal drug that reduces intracellular sodium and calcium accumulation during ischemia, thus potentially limiting myocardial ischemia. It remains unknown, however, if the drug can play a role in the pathophysiology of periprocedural myocardial infarction. The aim of this study was to verify in a randomized study if pretreatment with ranolazine before percutaneous coronary intervention (PCI) has any protective effect on periprocedural myocardial damage. METHODS Seventy patients with stable angina (age 62 ± 18 years, 42 men) scheduled for elective coronary intervention entered a randomized, double-blind, placebo-controlled pilot trial. For 7 days before the procedure, 35 patients were assigned to receive ranolazine (1,000 mg twice daily) and 35 patients had placebo. Creatine kinase-MB and troponin I levels were measured at baseline and at 8 and 24 hours postprocedure. RESULTS Comparison between the 2 groups did not show any difference in clinical features, extent of coronary artery disease, and technical aspects of PCI. Periprocedural myocardial infarction (ie, postprocedural increase of creatine kinase-MB ≥ 3 times above the upper limit of normal) was less commonly seen after PCI in the ranolazine than in the placebo group (6% vs 22%, P = .041). Detection of markers of myocardial injury above the upper limit of normal was less common [corrected] in the ranolazine vs placebo group: 23% vs 40% for creatine kinase-MB (P = .010) and 31% vs 48% for troponin I (P = .011). [corrected] Postprocedural peak markers levels were also significantly lower in the ranolazine vs placebo group (creatine kinase-MB: 3.1 ± 15.0 and 7.7 ± 19.1 ng/mL, P < .05; troponin I: 0.15 ± 0.35 and 0.47 ± 0.49 ng/mL, P < .05). No significant adverse effect was reported by the 2 groups of patients. CONCLUSIONS Pretreatment with ranolazine 1,000 mg twice daily for 7 days significantly reduced procedural myocardial injury in elective PCI.

Safety profile of mineralocorticoid receptor antagonists: Spironolactone and eplerenone

Spironolactone was first developed over 50 years ago as a potent mineralocorticoid receptor antagonist with undesirable side effects; it was followed a decade ago by eplerenone, which is less potent but much more mineralocorticoid receptor-specific. From a marginal role as a potassium-sparing diuretic, spironolactone has been shown to be an extraordinarily effective adjunctive agent in the treatment of progressive heart failure. Also, spironolactone is safe and protective in arterial hypertension, particularly in patients with so-called resistant hypertension. Eplerenone is the second oral aldosterone antagonist available for the treatment of arterial hypertension and heart failure. Treatment with eplerenone has been associated with decreased blood pressure and improved survival for patients with heart failure and reduced left ventricular ejection fraction. Due to the selectivity of eplerenone for the aldosterone receptor, severe adverse effects such as gynecomastia and vaginal bleeding seem to be less likely in patients who take eplerenone than in those who take spironolactone. The most common and potentially dangerous side effect of spironolactone--hyperkalemia--is also observed with eplerenone but the findings from clinical trials do not indicate more hyperkalemia induced drug withdrawals. Treatment with eplerenone should be initiated at a dosage of 25mg once daily and titrated to a target dosage of 50mg once daily preferably within 4 weeks. Serum potassium levels and renal function should be assessed prior to initiating eplerenone therapy, and periodic monitoring is recommended, especially in patients at high risk of developing hyperkalemia.

Meta-Analysis of Net Long-Term Benefit of Different Therapeutic Strategies in Patients With Cryptogenic Stroke and Patent Foramen Ovale

We pooled available data on follow-up events in patients with patent foramen ovale and cryptogenic stroke to evaluate the net clinical benefit of different therapeutic strategies (percutaneous closure vs antiplatelet vs anticoagulant therapy). MEDLINE/PubMed and Cochrane databases and reviewed cited references to identify relevant studies were used; 3,311 patients from 21 clinical studies, both observational and randomized, with follow-up ≥12 months were overall included. Net clinical benefit was evaluated considering the cumulative incidence of both stroke and/or transient ischemic attack and major bleeding events. Anticoagulant therapy was more effective than antiplatelet therapy in preventing recurrent stroke and/or transient ischemic attack (event rates: 7.7% vs 9.8%, respectively, p = 0.03), but at the price of more than sixfold greater risk of major bleeding (7.1% vs 1.3%; odds ratio 6.49, 95% confidence interval 3.25 to 12.99, p <0.00001). Patent foramen ovale closure was associated over the long term with significant net clinical benefit versus both antiplatelet and anticoagulant therapy; such benefit was driven by 50% relative reduction of stroke and/or transient ischemic attack versus antiplatelet therapy and by 82% relative reduction of major bleeding versus anticoagulant therapy. In conclusion, results of this large study-level meta-analysis may influence practice patterns in patients with patent foramen ovale and cryptogenic stroke; an individualized approach tailored on both the risk of recurrent cerebral events and the bleeding risk should be used to identify the best therapeutic option (percutaneous closure vs antiplatelet therapy vs anticoagulant therapy).

Clinical epidemiology, management and outcome of acute coronary syndromes in the Italian network on acute coronary syndromes (IN-ACS Outcome study)

Background: The Italian network on acute coronary syndromes outcome (IN-ACS Outcome) study is a nationwide observational, multicenter study with the aim to describe clinical epidemiology, management, 30-days and one-year outcomes of ACS in Italy. Methods: All consecutive patients admitted for ACS to 38 hospitals, between December 2005 and February 2007, were enrolled in the study. Patient in-hospital details and follow-up data at 30-days and one-year were collected using a web-based CRF and stored in a central database. Results: A total of 6045 patients (age 68 ± 13 years) were enrolled: 2313 patients (38.3%) had ST elevation myocardial infarction (STEMI) and 3732 (61.7%) patients had NSTE-ACS. Primary PCI was performed in 1085 (46.9%) STEMI patients, thrombolysis in 590 (25.5%) patients, whereas 638 (27.6%) patients were not reperfused. Among patients with NSTE-ACS, coronary angiography was performed in 2797 (75%) patients, PCI in 1797 (48.2%) patients and CABG in 213 (5.7%) patients. Thirty-days and one-year mortality rates were 5.8% and 9.8%, in STEMI patients and 3.1% and 8.6%, in NSTE-ACS patients. Conclusions: The IN-ACS Outcome study showed that the management of ACS is still suboptimal. Although 30-days mortality is low, the one-year mortality is still substantial.