ALLiance for sEcondary PREvention after an acute coronary syndrome. The ALLEPRE trial: A multicenter fully nurse-coordinated intensive intervention program.

The main objective of cardiovascular disease prevention is to reduce morbidity and mortality by promoting a healthy lifestyle, reducing risk factors, and improving adherence to medications. Secondary prevention after an acute coronary syndrome has proved to be effective in reducing new cardiovascular events, but its limited use in everyday clinical practice suggests that there is considerable room for improvement. The short-term results of evidence-based studies of nurse-coordinated secondary prevention programs have been positive, but there is a lack of long-term outcome data. The Alliance for the Secondary Prevention of Cardiovascular Disease in the Emilia-Romagna region (ALLEPRE) is a multicenter, randomized, controlled trial designed to compare the effects of a structured nurse-coordinated intensive intervention on long-term outcomes and risk profiles after an acute coronary syndrome with those of the standard of care. All of the patients randomized to the intervention group take part in 9 one-to-one sessions with an experienced nurse from the participating centers with the aim at promoting healthy lifestyles, reducing risk factors, and increasing adherence to medication over a mean period of 5 years. The primary clinical end point is the reduction in the risk of the 5-year occurrence of major adverse events (a composite of cardiovascular mortality, nonfatal reinfarction, and nonfatal stroke). The primary surrogate end point is the achievement of prespecified targets relating to classical risk factors, lifestyle modifications, and adherence to pharmacological therapy after 2 years of follow-up. Coronary heart disease is a chronic degenerative disease, and patients who recover from an acute coronary syndrome (ACS) are at high risk of developing recurrent events.1 Although secondary prevention measures have proved to be effective and are strongly recommended by all of the international guidelines,2., 3. the 4 EUROASPIRE surveys4., 5., 6., 7., 8. showed that there was still a high prevalence of conventional risk factors, that secondary prevention measures were inadequately implemented, and that their main goals were often not reached. In addition, there were considerable discrepancy in secondary prevention practices between centers and countries, and a widespread underuse of cardiac prevention and rehabilitation programs despite their demonstrated effectiveness in reducing cardiovascular risk over time.9., 10. Over the last 10 years, nurses have been increasingly involved in successful cardiovascular risk management,11., 12., 13. but although this has improved levels of cardiovascular risk, no clear reduction in hard end points such as major cardiovascular adverse events and mortality has been demonstrated.10 The aim of the ALLEPRE trial is to evaluate the benefit of a homogeneous, structured, secondary prevention intervention program, fully coordinated by nurses from in- and outpatient clinics, in terms of cardiovascular risk profiles and major clinical events in ACS patients living in the large Emilia-Romagna region of Italy.

Assessing MICRO-vascular resistances via IMR to predict outcome in STEMI patients with multivessel disease undergoing primary PCI (AMICRO): Rationale and design of a prospective multicenter clinical trial.

BACKGROUND: In STEMI patients treated with primary percutaneous coronary angioplasty (PPCI) the evaluation of coronary microcirculatory resistance index (IMR) predict the extent of microvascular damage and left ventricular (LV) remodeling. However, the impact of IMR on the clinical outcome after PPCI in patients with multivessel disease (MVD) remains unsettled. AIM: We designed a prospective multicenter controlled clinical trial to evaluate the prognostic value of IMR in terms of clinical outcome and left ventricular remodeling in STEMI patients with MVD undergoing PPCI. METHODS AND DESIGN: The study will involve 242 patients with MVD defines as the presence of at least a non-culprit lesion of >50% stenosis at index coronary angiography. Both fractional flow reserve (FFR) and IMR will be measured in the infarct-related artery (IRA) after successful PPCI. Measurements of FFR and IMR will be repeated in the IRA and performed in the non-culprit vessels at staged angiography. The non-culprit vessel lesions will be treated only in the presence of a FFR<0.75. A 2D echocardiographic evaluation of the left ventricular (LV) volumes and ejection fraction will be performed before hospital discharge and at 1-year follow-up. The primary end-point of the study will be the composite of cardiovascular death, re-hospitalization for heart failure and resuscitation or appropriate ICD shock during 1-year of follow-up. Secondary end-points will be the impact of IMR in predicting LV remodeling during follow-up and correlations between IMR and ST-segment resolution. Other secondary endpoints will be need for new revascularization, stent thrombosis and re-infarction of the non-culprit vessels territory. IMPLICATIONS: If IMR significantly correlates with differences in outcome and LV remodeling, it will emerge as a potential prognostic index after PPCI in patients with MVD.

Fractional Flow Reserve Evaluation and Chronic Kidney Disease: Analysis From a Multicenter Italian Registry (the FREAK Study).

OBJECTIVES: To establish if the presence of chronic kidney disease (CKD) influences fractional flow reserve (FFR) value in patients with intermediate coronary stenosis. BACKGROUND: FFR-guided coronary revascularization reduces cardiac adverse events in patients with coronary artery disease. CKD impairs microcirculation and increases cardiovascular risk. Whether CKD presence may limit FFR accuracy is unknown. METHODS: We used data from a multicenter prospective registry enrolling 1.004 patients undergoing FFR evaluation for intermediate stenosis. We assessed the relationship between clinical and angiographic variables and FFR measurement. CKD was defined as CrCl value ≤45 ml/min. FFR value was considered potentially flow-limiting, and therefore positive, if ≤0.80. The index of microcirculatory resistance (IMR) was calculated in 20 patients stratified according CrCl value (single-center substudy). RESULTS: FFR measurement was positive in 395 (39%) patients. Overall, 131 (13%) patients had CKD. Patients with CrCl ≤45 ml/min showed significantly higher FFR values as compared to the others (0.84 ± 0.07 vs. 0.81 ± 0.08, p < 0.001). Positive FFR occurrence was lower in patients with CrCl ≤45 ml/min (27% vs. 41%, p < 0.01). After multivariable analysis, diabetes (HR 1.07, 95%CI 1.008-1.13, p = 0.03), left anterior descending (HR 1.35, 95%CI 1.27-1.43, p < 0.001) and CrCl ≤45 ml/min (HR 0.92, 95%CI 0.87-0.97, p = 0.005) emerged as independent predictors of FFR measurement. Accordingly, IMR values were higher in patients with CrCl ≤45 ml/min (32 U [28245] vs. 16 U [11220], p < 0.01). CONCLUSIONS: FFR and IMR measurements differ between CKD patients and those with normal renal function. Flow-limiting FFR is less frequent in patients with CrCl ≤45 ml/min. © 2015 Wiley Periodicals, Inc.

New-generation drug-eluting stents reduce stent thrombosis and myocardial infarction: a propensity-score-adjusted analysis from the multicenter REAL registry (REgistro Regionale AngiopLastiche Dell'Emilia-Romagna).

OBJECTIVES: The aim of this study was to compare long-term clinical outcomes in patients treated with new-generation drug-eluting stent (DES) or early-generation DES in a real-world registry. BACKGROUND: New-generation DESs have proved to be more effective and safer than early-generation DES in randomized trials. However, the effects of new-generation DES versus early-generation DES in everyday clinical practice deserve further verification. METHODS: A propensity-score and inverse-probability weighted analysis of 5,332 patients undergoing DES implantation (2,557 new-generation and 2,775 early-generation) between January 1, 2007 and June 30, 2011 was performed, with a median follow-up of 3 years. We assessed the incidence of major adverse cardiovascular events (MACE: all-cause death, nonfatal myocardial infarction [MI], and target vessel revascularization [TVR]), and angiographic stent thrombosis (ST) during follow-up. RESULTS: At 3-years, new-generation DES in comparison with early-generation DES were associated with a reduced risk of MI (5% versus 7.4%, hazard ratio [HR]=0.65, 95% confidence interval [CI]=0.51-0.82, P=0.0004) and angiographic ST (0.5% vs. 1.1%, HR=0.35, 95% CI 0.17-0.72, P=0.004), whereas, the risk of TVR (10.9% vs. 13.5%; HR 0.99, 95% CI 0.84-1.16, P=0.99) and overall MACE was not significantly different (19.2% vs. 22.4%, HR=0.94, 95% CI=0.83-1.07, P=0.35). CONCLUSIONS: Our data from a large all-comers multicenter registry confirm that, in comparison with early-generation DES, the use of new-generation DES is associated with similar efficacy and increased long-term safety, because of a reduced risk of ST and MI.

Long-term outcome in patients with ST segment elevation myocardial infarction and multivessel disease treated with culprit-only, immediate, or staged multivessel percutaneous revascularization strategies: Insights from the REAL registry.

OBJECTIVES: To examine the differences in cardiac outcomes for patients with ST-elevation myocardial infarction (STEMI) and multivessel disease (MVD) as a function of whether they underwent culprit-only primary percutaneous coronary intervention (PPCI) or multivessel PCI, either during PPCI or as a staged procedure. BACKGROUND: MVD occurs in about 40% of patients presenting with STEMI, and it has been associated with a worse outcome compared to single-vessel disease. The most favorable PCI strategy for dealing with significant nonculprit lesions has to be established. METHODS: A total of 2061 STEMI patients with MVD undergoing PPCI, prospectively enrolled in the REAL Registry between July 2002 and December 2010, were considered: 706 underwent culprit-only PPCI; 367 multivessel PCI during the index procedure; 988 had a staged PCI within 60 days. Mortality and outcomes were calculated at 30 days and 2 years. RESULTS: At multivariate analysis, culprit-only PPCI was associated with higher rates of cardiac outcomes as compared to staged multivessel PCI, taken as reference [Hazard Ratio (HR): 2.81, 95% confidence interval (CI): 1.34-5.89, P = 0.006 for 30-day mortality, and HR: 1.93, 95% CI: 1.35-2.74, P = 0.0002 for 2-year mortality, respectively]. Short-term mortality rates were higher in multivessel PCI group as compared to staged PCI group (HR: 2.58, 95% CI: 1.06-6.26, P = 0.03); no differences were observed at 2-year follow-up (HR: 1.08, 95% CI: 0.64-1.82, P = 0.76). CONCLUSIONS: Our findings support the current guidelines recommendation to perform culprit-only PPCI in STEMI patients with MVD without hemodynamic compromise, followed by a staged PCI of noninfarct-related significant lesions.

Implantable cardioverter defibrillator system with floating atrial sensing dipole: a single-center experience.

BACKGROUND: The concept of a single-lead dual-chamber implantable cardioverter defibrillator (ICD) with floating sensing atrial dipole has been proven safe and functional. We report a single-center experience with this ICD system; the major focus of the work is on the recorded atrial activation and its stability on a medium term follow-up. METHODS: Thirteen patients received a DX ICD (BIOTRONIK SE & Co, Berlin, Germany) with the Linox Smart S DX(ProMRI) ICD lead; the implantation data were reported. Daily P- and R-wave sensing amplitude was collected and followed up during 200 days; their coefficient of variance (CV) was calculated. In addition, all the atrial and ventricular high-rate episodes were analyzed. RESULTS: The total x-ray exposure time was 3.9 ± 1.8 minutes. The overall mean sensing was 4.2 ± 1.9 mV for P wave and 12.9 ± 4.5 mV for R wave. The CV was significantly higher for the P-wave amplitude than for the R-wave one (0.25 ± 0.11 vs 0.08 ± 0.06; P < 0.001). A total of 27 high ventricular rate episodes were recorded and correctly discriminated by the device. Fifty-six high atrial rate episodes were recorded, 49 were true arrhythmic events. CONCLUSIONS: The single-lead ICD system with floating atrial dipole provides reliable atrial sensing amplitude over time. The physician, without the implantation of an additional lead, has the atrial information that may be used for the discrimination of supraventricular tachyarrhythmia/ventricular tachycardia, for the early detection of atrial fibrillation episodes and for the evaluation of changes in the patient's heart status.

Triple antithrombotic therapy in patients with atrial fibrillation undergoing coronary artery stenting: hovering among bleeding risk, thromboembolic events, and stent thrombosis.

Dual antiplatelet treatment with aspirin and clopidogrel is the antithrombotic treatment recommended after an acute coronary syndrome and/or coronary artery stenting. The evidence for optimal antiplatelet therapy for patients, in whom long-term treatment oral anticoagulation is mandatory, is however scarce. To evaluate the safety and efficacy of the various antithrombotic strategies adopted in this population, we reviewed the available evidence on the management of patients receiving oral anticoagulation, such as a vitamin-k-antagonists, referred for coronary artery stenting.Atrial fibrillation is the most frequent indication for oral anticoagulation. The need of starting antiplatelet therapy in this clinical scenario raises concerns about the combination to choose: triple therapy with warfarin, aspirin, and a thienopyridine being the most frequent and advised. The safety of this regimen appeared suboptimal because of an increased risk in hemorrhagic complications. On the other hand, the combination of oral anticoagulation and an antiplatelet agent is suboptimal in preventing thromboembolic events and stent thrombosis; dual antiplatelet therapy may be considered only when a high hemorrhagic risk and low thromboembolic risk are perceived. Indeed, the need for prolonged multiple-drug antithrombotic therapy increases the bleeding risks when drug eluting stents are used.Since current evidence derives mainly from small, single-center and retrospective studies, large-scale prospective multicenter studies are urgently needed.

One-year results from the Assessing MICRO-vascular resistances via IMR to predict outcome in ST-elevation myocardial infarction patients with multivessel disease undergoing primary PCI (AMICRO) trial.

Background: In ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary angioplasty (PPCI) the index of microcirculatory resistance (IMR) correlates to the extent of myocardial damage and left ventricular (LV) function recovery. Data on the IMR time-course and impact on clinical outcome in STEMI patients with multi-vessel disease (MVD) are scarce. Aims: We designed a prospective, multicenter clinical trial to assess the infarct-related artery (IRA)-IMR in STEMI patients with MVD undergoing PPCI and to explore its potential in relationship with outcome and LV remodeling. Methods: The study enrolled 242 STEMI patients with MVD. Both fractional flow reserve (FFR) and IMR of the IRA were assessed after successful PPCI. Then, FFR/IMR measurements were repeated in the IRA at a staged angiography, and FFR-guided angioplasty was performed in non-IRA lesions. The primary endpoint was the composite of cardiovascular death, re-infarction, re-hospitalization for heart failure, resuscitation or appropriate ICD shock at 1-year follow-up. Results: A significant improvement of IRA-IMR values (from 47.9 to 34.2, p < 0.0001) was observed early after PPCI. Staged FFR-guided angioplasty was performed in 102 non-IRA lesions. We failed to find a correlation between IRA-IMR, clinical events and LV remodeling. Notwithstanding, in patients with anterior STEMI an inverse correlation between initial IMR values and LV function at follow-up was observed. Conclusion: After successful PPCI, a significant proportion of patients with STEMI and MVD had coronary microvascular dysfunction as assessed by IMR that recovered early after reperfusion. Higher IMR values predicted lack of improvement of LV function only in anterior STEMI. Clinical trial registration: https://clinicaltrials.gov/, identifier [NCT02325973].

Comparison of 2-year clinical outcomes with sirolimus and paclitaxel-eluting stents for patients with diabetes: results of the Registro Regionale AngiopLastiche Emilia-Romagna Registry.

BACKGROUND: Long-term outcomes of percutaneous coronary interventions (PCI) with sirolimus-eluting stents (SES) compared to paclitaxel-eluting-stents (PES) in unselected diabetics in routine practice is still debated. OBJECTIVE: This study compared the 2-year incidence of MACE (all-cause mortality, nonfatal myocardial infarction and target vessel revascularization) of SES and PES in a real-world setting of patients with diabetes. DESIGN: Observational, multicenter, nonrandomized study. SETTING: Prospective web-based registry (REAL Registry; study period, 2002-2005) comprising all 13 hospitals performing PCI. PATIENTS: Among the 945 eligible patients treated with either SES alone (n = 606) or PES alone (n = 339), 29% were insulin-requiring, 72% had multivessel coronary disease, 26% had prior myocardial infarction and 10% had poor left ventricular function. MEASUREMENTS: Unadjusted and propensity score-adjusted 2-year clinical outcome. RESULTS: After propensity score adjustment, 2-year MACE incidence in the SES and PES groups was equivalent (23.3% vs. 23.7%, HR 1.01, 95%CI 0.72-1.42, P = 0.96). Adjusted 2-year angiographic stent thrombosis occurred in 1.1% of the SES patients versus 2.6% of the PES patients (P = 0.15). In this large, real-world, diabetic population treated with DES, there was no difference in outcome between SES and PES. Further studies are needed to demonstrate the long-term safety of different types of DES in patients with diabetes.

Twenty-four months clinical outcomes of sirolimus-eluting stents for the treatment of small coronary arteries: the long-term SES-SMART clinical study.

AIMS: It has been demonstrated that, in comparison with bare-metal stents (BMS), sirolimus-eluting stents (SES) reduce restenosis after the percutaneous revascularization of small coronary arteries, but the long-term clinical outcomes of this treatment have not yet been investigated. METHODS AND RESULTS: The long-term SES-SMART clinical study was a multicentre, prospective, randomized, single-blind study of 257 patients receiving a SES or BMS in a small coronary artery, who were evaluated at discharge, 30 days, 8 and 24 months after stenting. The clinical endpoint of the study was a 24 months composite of major adverse cardiac and cerebrovascular events, which included death, non-fatal myocardial infarction, ischaemia-driven target lesion revascularization (TLR), and cerebrovascular accident. The 24 months follow-up was completed by 254 patients (98.8%). The use of SES was associated with a significantly lower incidence of the clinical endpoint (12.6% vs. 33.1%; HR 0.30, 95% CI: 0.17-0.55; P < 0.0001), which was not only due to a reduction in TLR (7.9% vs. 29.9%; HR 0.30, 95% CI: 0.16-0.59; P < 0.0001), but also to a reduction in myocardial infarction (1.6% vs. 10.2%; HR 0.09, 95% CI: 0.01-0.66; P = 0.018). CONCLUSION: In comparison with BMS, the use of SES in the percutaneous revascularization of small coronary arteries is associated with improved clinical outcomes after 2 years follow-up.