Carlo Pierli

Impact of Iso-Osmolar Versus Low-Osmolar Contrast Agents on Contrast-Induced Nephropathy and Tissue Reperfusion in Unselected Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention (From the Contrast Media and Nephrotoxicity Following Primary Angioplasty for Acute Myocardial Infarction [CONTRAST-AMI] Trial)

Conflicting data have been reported on the effects of low-osmolar and iso-osmolar contrast media on contrast-induced acute kidney injury (CI-AKI). In particular, no clinical trial has yet focused on the effect of contemporary contrast media on CI-AKI, epicardial flow, and microcirculatory function in patients with ST-segment elevation acute myocardial infarction who undergo primary percutaneous coronary intervention. The Contrast Media and Nephrotoxicity Following Coronary Revascularization by Angioplasty for Acute Myocardial Infarction (CONTRAST-AMI) trial is a prospective, randomized, single-blind, parallel-group, noninferiority study aiming to evaluate the effects of the low-osmolar contrast medium iopromide compared to the iso-osmolar agent iodixanol on CI-AKI and tissue-level perfusion in patients with ST-segment elevation acute myocardial infarction. Four hundred seventy-five consecutive, unselected patients who underwent primary percutaneous coronary intervention were randomized to iopromide (n = 239) or iodixanol (n = 236). All patients received high-dose N-acetylcysteine and hydration. The primary end point was the proportion of patients with serum creatinine (sCr) increases ≥25% from baseline to 72 hours. Secondary end points were Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, increase in sCr ≥50%, increase in sCr ≥0.5 or ≥1 mg/dl, and 1-month major adverse cardiac events. The primary end point occurred in 10% of the iopromide group and in 13% of the iodixanol group (95% confidence interval -9% to 3%, p for noninferiority = 0.0002). A TIMI myocardial perfusion grade of 0 or 1 was present in 14% of patients in the 2 groups. No differences between the 2 groups were found in any of the secondary analyses of sCr increase. No significant difference in 1-month major adverse cardiac events was found (8% vs 6%, p = 0.37). In conclusion, in a population of unselected patients with ST-segment elevation acute myocardial infarction who underwent primary percutaneous coronary intervention, iopromide was not inferior to iodixanol in the occurrence of CI-AKI; no significant differences were found in terms of tissue-level reperfusion and major adverse cardiac events between the 2 contrast agents.

Long-Term Effectiveness and Safety of Sirolimus Stent Implantation for Coronary In-Stent Restenosis: Results of the TRUE (Tuscany Registry of Sirolimus for Unselected In-Stent Restenosis) Registry at 4 Years

OBJECTIVES The aim of this study was to evaluate the long-term clinical outcome of the efficacy and safety of sirolimus-eluting stents (SES) for in-stent restenosis (ISR) in the TRUE (Tuscany Registry of Unselected In-Stent Restenosis) database. BACKGROUND The TRUE registry demonstrated that SES in the treatment of bare-metal stent ISR is efficacious (5% of target lesion revascularization [TLR]) and safe (stent thrombosis <1%) at 9 months. Clinical outcome at 4 years is reported. METHODS A total of 244 patients with ISR who were treated with SES implantation represent the study population. The incidence of major adverse cardiac events was collected at 4 years. RESULTS At 4-year follow-up, overall mortality was 9.8% (24 patients). Cardiac death occurred in 11 (4.5%), nonfatal myocardial infarction in 8 (3.2%), and TLR in 27 (11.1%) patients for a cumulative event-free survival rate of 80.3%. Definite stent thrombosis occurred in 5 (2%) patients and possible stent thrombosis in 2 (0.8%). Diabetes remained an independent negative predictor of freedom from TLR (odds ratio [OR]: 0.38; 95% confidence interval [CI]: 0.20 to 0.71, p = 0.002) and major adverse cardiac events (OR: 0.38; 95% CI: 0.20 to 0.71, p = 0.002). CONCLUSIONS The clinical benefit of SES implantation for bare-metal stent ISR is maintained at 4 years with a low TLR rate and an overall incidence of stent thrombosis of 0.7% per year.

Reduced levels of putative endothelial progenitor and CXCR4+ cells in coronary artery disease: Kinetics following percutaneous coronary intervention and association with clinical characteristics

Levels of circulating endothelial progenitor cells (EPCs) and CXCR4-positive cells are decreased in patients with coronary artery disease (CAD); however, their ability to change in response to acute vascular injury remains to be elucidated. Progenitor and CXCR4-positive cells were analysed by flow cytometry from the peripheral blood of 23 healthy controls and 23 patients with CAD, of which 13 patients underwent angiogram and 10 patients received percutaneous coronary intervention (PCI) with stent implantation. Baseline levels of progenitor and CXCR4-positive cells were substantially reduced in CAD patients compared to controls, although they were still capable of increasing in response to vascular injury. Levels of progenitor and CXCR4-positive cells were increased to a greater extent in the PCI group compared to angiogram patients. At presentation, levels of putative endothelial progenitor and CXCR4-positive cells were found to be negatively correlated with disease severity. A one-year follow-up revealed that out of the cell populations examined, only levels of CXCR4-positive cells were positively correlated with angina frequency in the PCI group, but not in patients receiving angiogram. Baseline levels of progenitor cells are differentially increased depending upon the severity of vascular injury incurred, regardless of a significant deficit in baseline levels in CAD patients. Levels of putative EPCs and CXCR4-positive cells were negatively correlated with disease severity at presentation, however, only CXCR4-positive cells were associated with patient condition in a one-year follow-up.

The impact of gender on fractional flow reserve measurements.

AIMS Fractional flow reserve (FFR) allows accurate investigation of the functional significance of intermediate coronary stenoses. The present study set out to study the impact of gender on FFR measurements. METHODS AND RESULTS Three hundred and seventeen intermediate (40-70% at angiography) stenoses were assessed with FFR in 270 patients (mean age 65.8 ± 10.3 years, 84 females). Resting Pd/Pa (the ratio of mean blood pressure measured distal to the stenosis to mean aortic blood pressure in resting conditions), FFR (Pd/Pa during adenosine-induced hyperaemia) and the ΔPd/Pa (calculated as the change in Pd/Pa during hyperaemia) were measured. There was no difference in the location and degree of stenoses between genders (p>0.5). Similarly, there was no difference in age and in the prevalence of cardiovascular risk factors (all p>0.2). Resting Pd/Pa also did not differ between genders (0.92 ± 0.08 vs. 0.93 ± 0.05, p=0.23). In response to adenosine, however, a significantly larger ΔPd/Pa (0.14 ± 0.07 vs. 0.11 ± 0.07, p=0.001) and a significantly lower FFR (0.79 ± 0.12 vs. 0.82 ± 0.10, p=0.008) were observed in males. This difference was maintained in a multivariate regression analysis. CONCLUSIONS We observed gender-based differences in FFR data in daily routine. Further studies are necessary to test the mechanism of this observation and how these differences impact on the assessment of haemodynamically relevant stenoses.

Evaluating the safety of very short-term (10 days) dual antiplatelet therapy after Genous™ bio-engineered R stent™ implantation: the multicentre pilot Genous trial.

AIMS Percutaneous coronary stenting is synonymous with dual antiplatelet therapy, ranging from four weeks to lifelong. However, even short-term (four weeks) therapy with aspirin and thienopyridines is occasionally contraindicated. No study has ever appraised very short-term dual antiplatelet therapy after stenting. We thus aimed to exploit the pro-healing features of the Genous™ Bio-engineered R stent™ (Genous) (OrbusNeich Medical Technologies, Hong Kong, Peoples Republic of China) and evaluate the safety of a 10-day dual antiplatelet regimen after its implantation in up to 50 patients. METHODS AND RESULTS Forty-nine consecutive patients with de novo lesions located in vessels able to receive a 2.5 mm Genous stent were included. After stenting, they received lifelong aspirin plus clopidogrel for 10 days. The primary endpoint of the study was sudden cardiac death, myocardial infarction or angiographic evidence of stent thrombosis ascribable to the study stent. Almost 70% of patients effectively discontinued clopidogrel nine to 11 days after stenting. At three-month clinical follow-up, no patient had died or reached the primary endpoint (95%; confidence interval 0-7.3%). Repeat revascularisation occurred instead in three (6.1%[2.1-16.5%]), with target lesion revascularisation in two (4.1%[1.1-13.7%]). CONCLUSIONS Even very short-term dual antiplatelet therapy seems safe after coronary stenting with Genous in de novo coronary artery lesions located in secondary branch vessels. This preliminary exploratory study gives some support to planning a large trial to test the hypothesis of short dual antiplatelet therapy following Genous stent implantation.

B-type natriuretic peptide as an independent predictor of coronary disease extension in non-ST elevation coronary syndromes with preserved systolic function

Objective: B-type natriuretic peptide (BNP) has been employed as a risk marker in patients with coronary artery disease (CAD) with ST elevation and non-ST elevation. It is not yet established if early BNP measurements provide additional information to troponin and electrocardiographic analysis in patients without ventricular enlargement and systolic dysfunction. Design: This study compared BNP levels in patients with stable angina (SA) and acute coronary syndromes with non-ST elevation in relation to angiographic lesions (NSTEMI-ACS). Moreover, the diagnostic utility of BNP was determined using the receiver operating characteristic curve. Patients: 280 patients with CAD without ST elevation and preserved systolic function were studied. BNP samples were measured in all recruited patients within 24 hours of hospitalization. Results: BNP values increased progressively with the severity of diagnosis: SA (n = 85; 50.4 ± 50 pg/ml) NSTEMI-ACS (n = 195; 283 ± 269 pg/ml; p < 0.0001). The analysis of BNP in relation to the number of involved vessels demonstrated significantly increased levels in patients with multivessel disease compared to patients with 1- or 2-vessel disease (p < 0.001 and p < 0.003). Values of BNP >80 pg/ml were shown to be able to predict CAD severity and coronary vessel involvement (AUC = 0.80; p = 0.0001) with a sensitivity of 78% and a specificity of 72%. In multivariate analysis, BNP levels >80 pg/ml, CAD history, and ST deviation >2 mm were confirmed as independent predictors of CAD severity. Conclusions: Circulating BNP levels appear elevated in NSTEMI-ACS, without left ventricular systolic dysfunction. A BNP cut-off value of 80 pg/ml is a good predictor of CAD extension.

Takotsubo cardiomyopathy in a Caucasian Italian woman: Case report

BackgroundTakotsubo cardiomyopathy is an acute cardiac syndrome characterized by transient LV regional wall motion abnormalities (with peculiar apical ballooning appearance), chest pain or dyspnea, ST-segment elevation and minor elevations of cardiac enzyme levelsCase presentationA 68-year-old woman was admitted to the Emergency Department because of sudden onset chest pain occurred while transferring her daughter, who had earlier suffered a major seizure, to the hospital. The EKG showed sinus tachycardia with ST-segment elevation in leads V2–V3 and ST-segment depression in leads V5–V6, she was, thus, referred for emergency coronary angiography. A pre-procedural transthoracic echocardiogram revealed regional systolic dysfunction of the LV walls with hypokinesis of the mid-apical segments and hyperkinesis of the basal segments. Coronary angiography showed patent epicardial coronary arteries; LV angiography demonstrated the characteristic morphology of apical ballooning with hyperkinesis of the basal segments and hypokinesis of the mid-apical segments. The post-procedural course was uneventful; on day 5 after admission the echocardiogram revealed full recovery of apical and mid-ventricular regional wall-motion abnormalities.ConclusionTakotsubo cardiomyopathy is a relatively rare, unique entity that has only recently been widely appreciated. Acute stress has been indicated as a common trigger for the transient LV apical ballooning syndrome, especially in postmenopausal women. The present report is a typical example of stress-induced takotsubo cardiomyopathy in a Caucasian Italian postmenopausal woman.

B-type natriuretic peptide levels predict extent and severity of coronary disease in non-ST elevation coronary syndromes and normal left ventricular systolic function.

BACKGROUND B-type natriuretic peptide (BNP) has been used recently as a biological marker in patients with coronary artery disease (CAD) with ST-elevation, as well as without ST-elevation. BNP is able to predict systolic dysfunction, adding new prognostic information to existing traditional markers. However is not known if there is a relation between the quantity of BNP levels and the severity of coronary artery disease. METHODS This study compared B-type natriuretic peptide (BNP) levels in patients with stable angina (SA) and acute coronary syndromes (ACS) without ST-elevation in relation to angiographic lesions using TIMI and Gensini Scores. We studied 282 patients with CAD without ST elevation and preserved systolic function. BNP samples were measured in all recruited patients within 24 hours of hospitalization. RESULTS BNP values were progressively increased in relation to the severity of diagnosis: SA (52.6±49.4 pg/mL ) UA (243.3±212 pg/mL) NSTE-ACS (421.7±334 pg/mL) (p<0.0001 and p<0.007 respectively). No statistically significant difference was observed between patients with SA and controls (21.2±6.8 pg/mL). The analysis of BNP levels in relation to the number of involved vessels demonstrated significantly increased levels in patients with multivessel disease compared to patients with 1 or 2 vessel disease (1-86.2±46.3 pg/mL; 2-127±297 pg/mL; 3-295±318 pg/mL; 4-297±347 pg/mL p<0.001 and p<0.003). Evaluation of BNP using Gensini Score showed a strong relation between BNP and coronary disease extension (r=0.38 p<0.0001).This trend was maintained in all CAD groups (SA=r 0.54; UA r=0.36 NSTE-ACS r=0.28). CONCLUSIONS Circulating BNP levels appear elevated in ACS with diffuse coronary involvement, even in the absence of systolic dysfunction. BNP is also associated with multi-vessel disease and the extension of coronary disease.

Long-term clinical outcome of alternative treatment strategies for drug-eluting stents restenosis.

AIMS Due to the widespread use of drug-eluting stents (DES), in-DES restenosis is increasing. The aim of this study is to evaluate the clinical outcome of patients undergoing repeat percutaneous coronary intervention (PCI) for DES restenosis. METHODS AND RESULTS One hundred patients with 108 restenotic lesions using DES were consecutively enrolled in a single-arm 2-centre registry. The repeat-PCI was performed either with balloon angioplasty (POBA) or with DES implantation (homo-stent or hetero-stent). Major adverse cardiac events (MACE) occurrence was assessed long-term. Of the 108 DES restenotic lesions, 34 were treated with balloon angioplasty, 43 with homo-stent and 31 with hetero-stent implantation. Of the patients, 37% had diabetes mellitus, while 30% peripheral or carotid artery disease. Over a mean follow-up of 16.0+/-6.0 months, the rates of death, myocardial infarction (MI), and ischaemic driven target lesion revascularisation (IDTLR) in hetero-stent, homo-stent and POBA groups were respectively 0% vs. 5% vs. 3% (p=NS), 2% vs. 5% vs. 0% (p=NS) and 17% vs. 23% vs. 25% (p=NS). When comparing patients treated with POBA to those receiving hetero-/homo-DES, no significant difference in terms of IDTLR (25% vs. 20%; p=NS), MI (0% vs. 4%; p=NS) and overall MACE (25% vs. 23%, p=NS) appeared. The presence of previous MI (OR 0.05; 95% CI 0.01-0.3), first DES implanted for BMS restenosis (OR 0.16; 95% CI 0.02-0.99) and peripheral or carotid disease (OR 0.09; 95% CI 0.01-0.67) were negative independent predictors of freedom from IDTLR. CONCLUSIONS Repeat balloon angioplasty for DES restenosis showed similar clinical outcome compared to re-DES (homo- or hetero-) implantation and could be considered as first treatment strategy in this setting.

Beneficial effect of post-procedural abciximab in patients undergoing primary coronary angioplasty and presenting with the no-reflow phenomenon

We sought to investigate the effect of post-procedural abciximab on clinical outcome of patients presenting the no-reflow phenomenon after primary angioplasty. We retrospectively selected 38 patients who developed the no-reflow phenomenon after primary angioplasty: 18 received post-procedural abciximab, 20 age- and sex-matched patients who did not receive abciximab were considered as concurrent controls. At 6 months follow-up, the clinical course was uneventful in the abciximab group while the composite end-point of major adverse cardiac events occurred in 8 patients (40%) in the control group (P=0.009). ‘Rescue’ administration of abciximab is an effective option for the treatment of the no-reflow phenomenon determining significant prognostic improvements.