Massimo Margheri

Effect of heparin, aspirin, or alteplase in reduction of myocardial ischaemia in refractory unstable angina

399 out of 474 inpatients with unstable angina were monitored for 48 h and 97 of these were found to be refractory to conventional antianginal treatments and entered a randomised double-blind study. With the initial protocol heparin infusion or bolus were compared with aspirin; with a modified protocol, heparin infusion, the best of these three treatments, was compared with alteplase. Patients were monitored for 3 days after starting treatment and then observed clinically for 4 more days. On the first days of treatment heparin infusion significantly decreased the frequency of angina (by 84-94%), episodes of silent ischaemia (by 71-77%), and the overall duration of ischaemia (by 81-86%). Heparin bolus and aspirin were not effective. Alteplase caused small (non-significant) reductions on the first day only. Only minor bleeding complications occurred.

Ostial and midshaft lesions vs. bifurcation lesions in 1111 patients with unprotected left main coronary artery stenosis treated with drug-eluting stents: results of the survey from the Italian Society of Invasive Cardiology

AIMS In this study, we compared the cumulative risk of major adverse cardiac events (MACE) of patients with distal unprotected left main coronary artery (ULMCA) stenosis with those of patients with ostial and midshaft lesions treated with drug-eluting stent (DES). METHODS AND RESULTS The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study involving 19 high-volume Italian centres. We enrolled 1111 patients with ULMCA stenosis treated with DES. Major adverse cardiac events were defined as death, myocardial infarction, and target lesion revascularization. Three hundred and thirty-four patients had ostial or midshaft lesions (group 1) and 777 bifurcations (group 2). The adjusted hazards ratio of the risk of 2 year MACE of patients in group 2 vs. patients in group 1 was 1.50 (P = 0.024). However, we observed that there was a significant difference between patients with bifurcations treated with two stents and those in group 1 (P = 0.001), but not between patients with bifurcations treated with one stent and those in group 1 (P = 0.38). CONCLUSION Patients with bifurcations have a worse outcome than patients with ostial and midshaft lesions. However, the technique used to treat bifurcations has a significant impact on clinical outcomes.

Safety and efficacy of biodegradable vs. durable polymer drug-eluting stents: evidence from a meta-analysis of randomised trials

AIMS Drug-eluting stents (DES) are a major advance in interventional cardiology; however concerns have been raised regarding their long-term safety due to the permanent nature of the polymer. New generation stents with biodegradable polymers (BDS) have recently been developed. The aim of this study was to perform a meta-analysis of randomised controlled trials (RCTs) comparing the safety and efficacy profile of BDS vs. durable polymer DES. METHODS AND RESULTS The MEDLINE/CENTRAL and Google Scholar databases were searched for RCTs comparing safety and efficacy of BDS vs. DES. Safety endpoints were mortality, myocardial infarction (MI), and stent thrombosis (ST). Efficacy endpoints were target vessel revascularisation (TVR), target lesion revascularisation (TLR) and six-month in-stent late loss (ISLL). The meta-analysis included eight RCTs (n=7,481). At a median follow-up of nine months, as compared to DES, BDS use did not increase mortality (OR [95% CI] = 0.91 [0.69-1.22], p=0.53) or MI (OR [95% CI] = 1.14 [0.90-1.44], p=0.29). Rate of late/very late ST was significantly reduced in BDS patients (OR [95% CI] = 0.60 [0.39-0.91], p=0.02), as was six-month ISLL (mean difference [95% CI] = -0.07 [-0.12; -0.02] mm, p=0.004) in comparison with DES patients. Rates of TVR and TLR were comparable between BDS and DES. CONCLUSIONS BDS are at least as safe as standard DES with regard to survival and MI, and more effective in reducing late ST, as well as six-month ISLL. Further large RCTs with long-term follow-up are warranted to definitively confirm the potential benefits of BDS.

Transradial Versus Transfemoral Intervention for Acute Myocardial Infarction: A Propensity Score-Adjusted and -Matched Analysis From the REAL (REgistro regionale AngiopLastiche dell'Emilia-Romagna) Multicenter Registry

OBJECTIVES This study sought to assess whether transradial intervention, by minimizing access-site bleeding and vascular events, improves outcomes in patients with ST-segment elevation myocardial infarction compared with the transfemoral approach. BACKGROUND Bleeding and consequent blood product transfusions have been causally associated with a higher mortality rate in patients with myocardial infarction undergoing coronary angioplasty. METHODS We identified all adults undergoing percutaneous intervention for acute myocardial infarction in Emilia-Romagna, a region in the north of Italy of 4 million residents, between January 1, 2003, and July 30, 2009, at 12 referral hospitals using a region-mandated database of percutaneous coronary intervention procedures. Differences in the risk of death at 2 years between patients undergoing transfemoral versus transradial intervention, assessed on an intention-to-treat basis, were determined from vital statistics records and compared based on propensity score adjustment and matching. RESULTS A total of 11,068 patients were treated for acute myocardial infarction (8,000 via transfemoral and 3,068 via transradial route). According to analysis of matched pairs, the 2-year, risk-adjusted mortality rates were lower for the transradial than for the transfemoral group (8.8% vs. 11.4%; p = 0.0250). The rate of vascular complications requiring surgery or need for blood transfusion were also significantly decreased in the transradial group (1.1% vs. 2.5%, p = 0.0052). CONCLUSIONS In patients undergoing angioplasty for acute myocardial infarction, transradial treatment is associated with decreased 2-year mortality rates and a reduction in the need for vascular surgery and/or blood transfusion compared with transfemoral intervention.

ST-Segment Elevation Myocardial Infarction Due to Early and Late Stent Thrombosis. A New Group of High-Risk Patients

OBJECTIVES The aim of this retrospective study was to compare clinical and angiographic outcomes between patients presenting with ST-segment elevation myocardial infarction (STEMI) due to stent thrombosis (ST) and de novo coronary thrombosis. BACKGROUND There are limited data for procedural and mid-term outcomes of patients with ST presenting with STEMI. METHODS From January 2004 to March 2007, 115 definite ST patients were observed: 92 (80%) of them presented as STEMI and were compared with a consecutive group of 98 patients with de novo STEMI. All patients underwent primary percutaneous coronary intervention. Primary end points were successful angiographic reperfusion and distal embolization. Major adverse cardiovascular and cerebrovascular events (MACCE), evaluated at 6-month follow-up, were defined as death, nonfatal myocardial reinfarction, target vessel revascularization, and cerebrovascular accident. RESULTS Successful reperfusion rate was lower in patients with ST (p < 0.0001), whereas distal embolization rate was higher (p = 0.01) in comparison with patients with de novo STEMI. Stent thrombosis proved to be an independent predictor of unsuccessful reperfusion at propensity-adjusted binary logistic regression (odds ratio 6.8, p = 0.004). In-hospital MACCE rate was higher in patients with ST (p = 0.003), whereas no differences were observed at 6-month follow-up among hospital survivors between the 2 groups (p = 0.7). CONCLUSIONS Stent thrombosis identifies a subgroup of patients with STEMI with poor angiographic and early clinical outcomes, suggesting that the management of these patients should be improved.

Evidence for the Existence of a Functional Cardiac Renin-Angiotensin System in Humans

BACKGROUND The presence of mRNA for the essential components of the renin-angiotensin system (RAS) has been found in animal and human hearts. The present study was designed to provide evidence for the existence of a (functional) cardiac RAS. METHODS AND RESULTS Twenty-four patients with atypical chest pain undergoing coronary angiography for diagnostic purposes were investigated. The cardiac production rate of angiotensins was estimated by measurement of the cardiac extraction of 125I-angiotensin I and 125I-angiotensin II associated with the determination of endogenous angiotensins in aortic and coronary sinus blood in normal, low, or high sodium diets. In a normal sodium diet, angiotensin I and II aorta-coronary sinus gradients were tendentially negative (-1.8 +/- 2.5 and -0.9 +/- 1.7 pg/mL, respectively), and the amounts of angiotensin I and II added by cardiac tissues were 6.5 +/- 3.1 and 2.7 +/- 1.3 pg/mL, respectively. The low sodium diet caused a significant increase in both plasma renin activity (PRA) and angiotensin I concentration in aortic but not in coronary sinus blood, resulting in a more negative aorta-coronary sinus gradient (-9.7 +/- 3.1 pg/mL, P < .01). Angiotensin formation by PRA in blood during transcardiac passage increased (P < .001), whereas angiotensin I formed by cardiac tissues decreased dramatically. Accordingly, in the low sodium diet, 125I-angiotensin II extraction did not change, the cardiac fractional conversion rate of 125I-angiotensin I to 125I-angiotensin II notably decreased (P < .01), and angiotensin II formation by cardiac tissues was undetectable. The high sodium diet caused a decrease in PRA and no changes in cardiac extraction of radiolabeled angiotensins; conversely, angiotensin I formed by cardiac tissues, cardiac Ang I fractional conversion rate, and angiotensin II formed during transcardiac passage significantly (P < .01 for all) increased. CONCLUSIONS These results provide evidence for the existence of a functional cardiac RAS independent of but related to the circulating RAS.

Propafenone versus amiodarone in field treatment of primary atrial tachydysrhythmias

Thirty-nine patients with paroxysmal atrial fibrillation or supraventricular tachycardia randomly received amiodarone or propafenone intravenously at home. Fifteen patients received amiodarone and 24 received propafenone; 87.5% of the patients who received propafenone and 40% of the patients who received amiodarone were converted at home to sinus rhythm (P less than .005). The median time of conversion was 10 minutes (range 5 to 35) for propafenone and 60 minutes (range 20 to 130) for amiodarone (P less than 0.005). When either drug failed to terminate atrial tachydysrhythmias at home, the same drug always restored sinus rhythm with subsequent oral treatment during hospitalization. No major side effects were observed after the infusion of either drug. The incidence of minor side effects was not significantly different between the two drugs. Both the drugs are efficacious and safe in the acute management of primary supraventricular tachydysrhythmias. Propafenone showed a greater rapidity of action.

Early and Long-Term Clinical Results of AngioJet Rheolytic Thrombectomy in Patients With Acute Pulmonary Embolism

Anticoagulant and thrombolytic therapies are a mainstay in the management of acute pulmonary embolism (PE), especially when hemodynamic compromise is present. However, systemic drugs cannot achieve timely and effective treatment of acute PE in all patients. In such a setting, mechanical removal of thrombus from the pulmonary circulation holds the promise of significant clinical benefits, although it remains untested. We report early and long-term outcome of patients with massive or submassive acute PE treated with rheolytic thrombectomy by means of the 6Fr Xpeedior AngioJet device at our institution. Three main groups were defined pre hoc: subjects with severe (i.e., shock), moderate, or mild hemodynamic compromise. Technical and procedural successes, obstruction, perfusion and Miller indexes, and clinical events were appraised. In total 25 patients were treated with thrombectomy (8 in severe, 12 in moderate, and 5 in mild hemodynamic compromise). Technical and procedural successes were obtained in all patients, as confirmed by the significant improvement in obstruction, perfusion and Miller indexes overall, and in each subgroup (all p values <0.001). Improvement in obstruction, perfusion, and Miller indexes at the end of the procedure could also be confirmed in patients (n = 8) treated with local fibrinolysis and in the absence of concomitant thrombolysis (n = 17, p <0.05). Four patients died in hospital, all other patients but 1 were safely discharged after an appropriate hospital stay, and all were alive at long-term follow-up (median 61 months). In conclusion, this study supports at early and long-term follow-up the effectiveness and safety of rheolytic thrombectomy for PE.

Two-Year Clinical Outcome With Drug-Eluting Stents Versus Bare-Metal Stents in a Real-World Registry of Unprotected Left Main Coronary Artery Stenosis from the Italian Society of Invasive Cardiology

Data are limited about the relative efficacy of drug-eluting stents (DESs) versus bare-metal stents (BMSs) for the treatment of unprotected left main coronary artery (ULMCA) stenosis. The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study involving 19 high-volume Italian centers of patients with ULMCA stenosis treated using percutaneous coronary intervention (PCI). From January 2002 to December 2006, of 1,453 patients identified with ULMCA stenosis treated with PCI, 1,111 were treated with DESs and 342 were treated with BMSs. During a 2-year follow-up, risk-adjusted survival free from cardiac death was significantly higher in patients treated with DESs than in those treated with BMSs. The propensity-adjusted hazard ratio for risk of 2-year cardiac mortality after DES versus BMS implantation was 0.49 (95% confidence interval 0.32 to 0.77). The benefit of DESs in reducing cardiac mortality was obtained in the period from 3 to 6 months and maintained up to 2 years. In conclusion, for patients with ULMCA stenosis undergoing PCI, DES implantation was associated with higher adjusted rates of 2-year survival free from cardiac death. The benefit of DESs in reducing cardiac mortality was obtained in the period in which clinical manifestations of restenosis usually peak.

EFFECTS OF ISCHEMIA AND REPERFUSION ON QT DISPERSION DURING CORONARY ANGIOPLASTY

The effects of ischemia and reperfusion on QT interval dispersion (QTD: QTmax‐QTmin in the 12‐lead ECG) were analyzed in 15 patients (12 males, 57 ± 13 years) undergoing coronary angiopiasty (PTCA). AH patients had single‐vessel coronary artery disease (only one ≥ 85% stenosis in a major coronary artery) and normal left ventricular function. AH were in sinus rhythm with normal atrioventricular and intraventricular conduction on the surface ECG. No patient was on therapy that could affect the QT interval. The ECG was recorded (all 12 leads simultaneously) at 50 mm/s speed before the first balloon inflation, at the end of the first inflation during PTCA, and at 30″ and 60″ during reperfusion following the first inflation. In order to avoid ischemic preconditioning, only recordings of the first inflation were used. In each tracing QTmax and QTmin were evaluated. All values were rate corrected using a simple linear equation (QT linear corrected = QT + 0.154 [1‐RR]). QTD increased significantly during both ischemia and reperfusion. QTmax was not changed by ischemia and was increased by reperfusion. QTmin was reduced by ischemia and increased by reperfusion. These results indicate that both ischemia and reperfusion alter ventricular repolarization, inducing a less homogeneous ventricular recovery pattern.