Baseline white blood cell count is an independent predictor of long-term cardiovascular mortality in patients with non-ST-segment elevation acute coronary syndrome, but it does not improve the risk classification of the GRACE score.

OBJECTIVES: To investigate the prognostic significance of baseline white blood cell count (WBCc) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and its additive predictive value beyond the Global Registry of Acute Coronary Events (GRACE) score. METHODS: We included 1,315 consecutive NSTE-ACS patients. Patients were divided in quartiles according to the WBCc (cells per 1 mm(3)) i.e. Q1 <6,850, Q2 = 6,850-8,539, Q3 = 8,540-10,857 and Q4 ≥10,858. The study end point was 3-year cardiovascular death (CVD). RESULTS: The median age of the study population was 76 years. Overall, 335 patients (25.5%) died with 211 of these (16%) suffering from CVD. Patients in Q4 showed a higher cumulative probability of CVD compared to patients in Q1-Q3. On multivariable analysis, patients in Q4 were at higher risk of CVD [hazard ratio (HR) = 1.47, 95% confidence interval (CI) 1.09-1.98, p = 0.011]. WBCc as a continuous variable was also independently associated with the study end point (HR = 1.043; 95% CI 1.02-1.07; p = 0.001). However, the incorporation of WBCc into the GRACE score did not improve either prediction of risk (C-index = 0.796 for GRACE score with or without WBCc) or classification of risk [relative integrated discrimination improvement = 0.0154, 95% CI) -0.029 to 0.0618; continuous net reclassification improvement = -0.0676, 95% CI -0.2149-0.0738). CONCLUSIONS: WBCc was an independent predictor of 3-year CVD in patients with NSTE-ACS. However, it did not add prognostic information beyond the GRACE score.

Percutaneous revascularization of left main: role of imaging, techniques, and adjunct pharmacology.

Refinement of interventional techniques, adjunctive pharmacological therapy, and the introduction of drug-eluting stents have fostered new interest for the percutaneous treatment of unprotected left main coronary artery (ULMCA) stenosis. Several observational registries, some randomized trials and several meta-analyses have consistently shown no difference in mortality and myocardial infarction between percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery in patients with ULMCA stenosis, but a higher rate of target vessel revascularization in patients treated with PCI. As a consequence, PCI of ULMCA stenosis has been upgraded to class IIa or IIb indication in the current European or American practice guidelines. However, several critical issues should be properly addressed when pursuing a percutaneous strategy for the treatment of ULMCA stenosis, such as the use of IVUS for procedural guidance, assessment of disease location, optimal technique for distal ULMCA stenosis, risk of stent thrombosis, optimal duration of dual antiplatelet therapy, and the most appropriate strategy for post-procedure follow up. Multidisciplinary team approach remains essential to provide a balanced information to the patient and to offer the beast treatment option.

Revascularization of unprotected left main coronary artery disease: strategy selection and systematic risk assessment.

Refinement of interventional techniques, adjunctive pharmacological therapy, and the introduction of drug eluting stents have fostered new interest for the percutaneous treatment of unprotected left main coronary artery (ULMCA) stenosis. Several observational registries, some randomized controlled trials and several meta-analyses have consistently shown no difference in mortality and myocardial infarction between percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery in patients with ULMCA stenosis, but a higher rate of target vessel revascularization in patients treated with PCI. As a consequence, PCI of ULMCA stenosis has been upgraded to class IIa or IIb indication in the current European or American College of Cardiology/American Heart Association practice guidelines. Although these results are promising, they do not still represent enough evidence for extending PCI of ULMCA stenosis to current clinical practice. The EXCEL trial will address the value of PCI in relation to CABG for the treatment of ULMCA stenosis in more than 2000 patients. A major breakthrough of the SYNTAX trial has been the demonstration of an interaction between the coronary complexity and the revascularization strategy, suggesting that optimal risk stratification is a key element when deciding the best strategy of revascularization in this high-risk group of patients. Multidisciplinary team approach remains essential to provide a balanced information to the patient and to offer the beast treatment option.

Absence of PCR-detectable human papilloma virus in erythroplasia of Queyrat using a comparative control group.

OBJECTIVES: High-risk human papillomavirus (HPV) types have been linked with genital carcinomas. However, the exact relation between HPV and erythroplasia of Queyrat (EQ), for example, in-situ carcinoma of the glans and prepuce, is still unclear. The aim of this study was to detect the presence of lesional HPV-DNA in patients with EQ. METHODS: Paraffin-embedded biopsies were obtained from the glans or inner foreskin of 11 adult uncircumcised patients (mean age 67.7 years; range 57-79) with EQ. An equal number of randomly selected uncircumcised healthy control patients underwent a single brush cytology smear of the penile mucosa. Biopsy specimens and brushings were then assayed by a highly sensitive two-step nested PCR technique based on MY11/MY09 consensus primers and general GP5+/GP6+ PCR primers, followed by cycle sequencing. Statistical evaluation was performed using conditional logistic regression analysis. RESULTS: None of the EQ or control samples proved to be positive for the presence of HPV-DNA. CONCLUSIONS: The findings do not support the hypothesis that there is a considerable risk of EQ development in patients with HPV infection. The prevalence of HPV infection in patients with EQ has rarely been investigated and available data are relatively scant and controversial. Therefore, the relation between HPV infection and the risk of progression of EQ into squamous cell carcinoma remains a matter of debate, and further investigations are needed in order to confirm the role of HPV in delineating this risk.

Diagnostic performance of standard electrocardiogram for prediction of infarct related artery and site of coronary occlusion in unselected STEMI patients undergoing primary percutaneous coronary intervention.

AIMS: To evaluate the relationship between ECG patterns and infarct related artery (IRA) in an all-comer population with ST-segment elevation myocardial infarction (STEMI) and validate current criteria for identifying IRA (right coronary artery (RCA) versus left circumflex artery (LCA)) in inferior STEMI and for diagnosing left main (LM) or left anterior descendent artery occlusion (LAD) in anterior STEMI. METHODS AND RESULTS: We retrospectively analysed ECGs at presentation and coronary angiogram in 885 consecutive patients undergoing primary percutaneous coronary intervention. Six ECG patterns were identified: anterior-STEMI (n=433; 49.0%), inferior-STEMI (i=365; 43.0%), lateral-STEMI (n=43; 5.0%), left bundle branch block (n=26; 3.0%), posterior-STEMI (n=7; 1.0%) and de Winter sign (n=7; 1.0%). The last two ECG patterns were univocally associated with LCA and proximal LAD occlusion respectively. In patients with inferior STEMI, predefined ECG algorithms showed high sensitivity(>90%) for RCA occlusion and high specificity(>90%) for LCA. The diagnostic performance was mainly determined by RCA dominance. In anterior STEMI the vectorial analysis of ST deviation in both frontal and horizontal planes could identify patients with LM/proximal LAD occlusion (adjusted-odds ratio for in-hospital mortality =2.45, 95% confidence interval: 1.31-4.56, p = 0.005) with low sensitivity (maximum 60%; using ST-depression in lead II, III, aVF + ΣSTE aVR + V1-ST depression V6≥0) and high specificity (maximum 95%; using ST-depression in inferior leads + ST-depression in V6). CONCLUSION: In STEMI undergoing primary percutaneous coronary intervention, six ECG patterns can be identified with a non-univocal relationship to the IRA. In inferior STEMI, vectorial analysis of ST deviation identifies IRA with a high appropriateness only when RCA is the dominant artery. In anterior STEMI, criteria derived from both frontal and horizontal planes identify LM/proximal LAD occlusion with high specificity but low sensitivity.

Predictors of complicated athero-thrombotic lesions in non-ST segment acute coronary syndrome.

AIMS: Non-ST segment elevation acute coronary syndrome (NSTE-ACS) is a heterogeneous syndrome in terms of patho-physiological mechanisms and prognosis. We sought to investigate the clinical features associated with complicated athero-thrombotic (CAT) coronary lesions and their prognostic relevance in NSTE-ACS. METHODS: We enrolled 701 consecutive NSTE-ACS patients without previous coronary bypass undergoing coronary angiography. The study population was divided into two groups according to the presence/absence of angiographic signs of endoluminal thrombi and/or plaque rupture, defined as CAT lesions. Multivariable analyses were used to identify predictors of CAT lesions. Their relation to composite endpoint of death, re-myocardial infarction, and re-unstable angina was investigated with the use of multivariable logistic regression. RESULTS: Patients with CAT lesions (n = 279, 40%) had a higher incidence of the combined endpoint (11.5 vs. 4.3%; P < 0.001). On multivariable analysis male sex [odds ratio (OR) 1.64, 95% confidence interval (CI) 1.17-2.30, P = 0.004], previous percutaneous coronary intervention (PCI) (OR 0.48, 95% CI 0.32-0.72, P < 0.001), severe angina (OR 1.72, 95% CI 1.18-2.52, P = 0.005) and anterior (i.e. V1-V4) ST segment depression (STD) were independently associated with CAT lesions (OR 1.71, 95% CI 1.14-2.57, P = 0.01). After adjustment for the Global Registry of Acute Coronary Events (GRACE) score only the presence of anterior STD emerged as an independent predictor of the clinical endpoint (OR 2.68, 95% CI 1.38-5.20, P = 0.003). The incorporation of anterior STD into the GRACE risk score showed an important trend toward improving prediction of endpoint as assessed by c-statistic (0.72 vs. 0.67; P = 0.08). CONCLUSION: In patients with NSTE-ACS male sex, severe angina and anterior STD were associated with an increased risk of CAT lesions. Patients with anterior STD were also at increased risk of in-hospital clinical events.

Risk of stroke with coronary artery bypass graft surgery compared with percutaneous coronary intervention.

OBJECTIVES: This study sought to determine whether coronary artery bypass graft (CABG) surgery is associated with an increased risk of stroke compared with percutaneous coronary intervention (PCI). BACKGROUND: Some, but not all, randomized trials have reported increased rates of stroke with CABG compared with PCI. However, all these studies were powered insufficiently to examine differences in the risk of stroke reliably. METHODS: We performed a meta-analysis of 19 trials in which 10,944 patients were randomized to CABG versus PCI. The primary end point was the 30-day rate of stroke. We also determined the rate of stroke at the midterm follow-up and investigated whether there was an interaction between revascularization type and the extent of coronary artery disease on the relative risk of stroke. RESULTS: The 30-day rate of stroke was 1.20% after CABG compared with 0.34% after PCI (odds ratio: 2.94, 95% confidence interval: 1.69 to 5.09, p < 0.0001). Similar results were observed after a median follow-up of 12.1 months (1.83% vs. 0.99%, odds ratio: 1.67, 95% confidence interval: 1.09 to 2.56, p = 0.02). The extent of coronary artery disease (single vessel vs. multivessel vs. left main) did not affect the relative increase in the risk of stroke observed with CABG compared with PCI at either 30 days (p = 0.57 for interaction) or midterm follow-up (p = 0.08 for interaction). Similar results were observed when the outcomes in 33,980 patients from 27 observational studies were analyzed. CONCLUSIONS: Coronary revascularization by CABG compared with PCI is associated with an increased risk of stroke at 30 days and at the mid-term follow-up.

The role of percutaneous balloon aortic valvuloplasty as a bridge for transcatheter aortic valve implantation.

AIMS: Many inoperable patients with severe aortic stenosis (AS) are not immediately eligible for transcatheter aortic valve implantation (TAVI). We evaluated the role of percutaneous balloon aortic valvuloplasty (BAV) in this setting. METHODS AND RESULTS: Among 210 consecutive patients referred to our institution for BAV, we identified three groups: immediately eligible for TAVI (n=65, 31%), excluded from TAVI (n=67, 32%), BAV as a bridge to TAVI (n=78, 37%). This last group comprised patients with low left ventricular ejection fraction, frailty or enfeebled status, symptoms of uncertain origin, critical conditions, moderate-to-severe mitral valve regurgitation, need of major non-cardiac surgery. Outpatient clinic visit and echocardiography were performed around one month after BAV to decide the final therapeutic strategy. Mean age was 81±8 years and the vast majority of patients had comorbidities and high-risk features. The incidence of periprocedural adverse events was 6.4%: 5.1% death (four patients: one procedural complication, three, natural disease progression), 1.3% minor stroke. After BAV, 46% of these patients were deemed eligible for TAVI, and 28% for cardiac surgery. Patients who underwent TAVI after bridge BAV showed 94% 30-day survival. CONCLUSIONS: BAV is a safe and effective tool to bridge selected patients to TAVI when indications are not obvious.

Pre-hospital ECG in patients undergoing primary percutaneous interventions within an integrated system of care: reperfusion times and long-term survival benefits.

AIMS: Treatment delay is a powerful predictor of survival in STEMI patients undergoing primary PCI. We investigated the effectiveness of pre-hospital triage with direct referral to PCI, alongside more conventional referral strategies. METHODS AND RESULTS: From January 2003 to December 2007, 1,619 STEMI patients were referred for primary PCI at our cathlab through two main triage groups: i.e., 1) following pre-hospital triage (n=524), 2) via more conventional triages (n=1,095) represented by the S. Orsola-Malpighi hospital emergency department triage (hub hospital) and local hospital triage. Pre-hospital diagnosis was associated with a 76 minute reduction in pain-to-balloon time (143 [107-216] vs. 219 [149-343], p=0.001) allowing mechanical revascularisation within 90 minutes from the first medical contact in the vast majority of the patients (>80%). Clinically, pre-hospital triage showed no significant reductions in terms of adjusted long-term mortality (HR 0.81, 95% CI 0.61-1.08; p=0.16) in the overall population. However, significant adjusted survival benefits were observed in high-risk groups (i.e., cardiogenic shock, TIMI risk score >30, diabetes mellitus). CONCLUSIONS: This study shows that pre-hospital diagnosis allows for significant reductions in primary PCI treatment delays and suggests the hypothesis that this referral strategy might provide long-term survival benefits especially in high-risk patients.

Short- and long-term prognostic significance of ST-segment elevation in lead aVR in patients with non-ST-segment elevation acute coronary syndrome.

We sought to evaluate the prognostic significance of ST-segment elevation (STE) in lead aVR in unselected patients with non-STE acute coronary syndrome (NSTE-ACS). We enrolled 1,042 consecutive patients with NSTE-ACS. Patients were divided into 5 groups according to the following electrocardiographic (ECG) patterns on admission: (1) normal electrocardiogram or no significant ST-T changes, (2) inverted T waves, (3) isolated ST deviation (ST depression [STD] without STE in lead aVR or transient STE), (4) STD plus STE in lead aVR, and (5) ECG confounders (pacing, right or left bundle branch block). The main angiographic end point was left main coronary artery (LM) disease as the culprit artery. Clinical end points were in-hospital and 1-year cardiovascular death defined as the composite of cardiac death, fatal stroke, and fatal bleeding. Prevalence of STD plus STE in lead aVR was 13.4%. Rates of culprit LM disease and in-hospital cardiovascular death were 8.1% and 3.8%, respectively. On multivariable analysis, patients with STD plus STE in lead aVR (group 4) showed an increased risk of culprit LM disease (odds ratio 4.72, 95% confidence interval [CI] 2.31 to 9.64, p <0.001) and in-hospital cardiovascular mortality (odds ratio 5.58, 95% CI 2.35 to 13.24, p <0.001) compared to patients without any ST deviation (pooled groups 1, 2, and 5), whereas patients with isolated ST deviation (group 3) did not. At 1-year follow-up 127 patients (12.2%) died from cardiovascular causes. On multivariable analysis, STD plus STE in lead aVR was a stronger independent predictor of cardiovascular death (hazard ratio 2.29, 95% CI 1.44 to 3.64, p <0.001) than isolated ST deviation (hazard ratio 1.52, 95% CI 0.98 to 2.36, p = 0.06). In conclusion, STD plus STE in lead aVR is associated with high-risk coronary lesions and predicts in-hospital and 1-year cardiovascular deaths in patients with NSTE-ACS. Therefore, this promptly available ECG pattern could be useful to improve risk stratification and management of patients with NSTE-ACS.

Prognostic significance of mean platelet volume on admission in an unselected cohort of patients with non ST-segment elevation acute coronary syndrome.

Mean platelet volume (MPV) has been proposed as a marker of platelet reactivity and cardiovascular risk. Its prognostic significance has not been thoroughly investigated in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). We included 1,041 consecutive patients with NSTE-ACS. Patients were divided in quartiles according to the MPV value on admission (fl) i.e. Q1<7.5; Q2=7.5-8.0; Q3=8.1-8.8; Q4≥8.9. The primary study endpoint was the composite of cardiovascular death and re-myocardial infarction (MI) at one year. Secondary study endpoints were individual cardiovascular death and re-MI. Patients in Q4 were older, had a higher prevalence of previous MI, peripheral artery disease and advanced Killip class compared to patients in Q1-Q3. Elevated MPV levels (Q4) was independently associated with gender, smoking status, platelet count and creatinine level. Overall, 210 patients (20.2%) reached the primary endpoint, 124 (12.1%) died from cardiovascular causes and 125 (12.0%) suffered from re-MI. On multivariable analysis patients in Q4 were at higher risk of primary endpoint (HR=1.41; 95%CI 1.06-1.89; p=0.02) whilst the association with cardiovascular death and re-MI was attenuated. MPV as continuous variable was independently associated with both primary endpoint (HR=1.19; 95%CI 1.06-1.33; p=0.003) and cardiovascular death (HR=1.23; 95%CI 1.06-1.42, p=0.006). The incorporation of MPV into a comprehensive model of risk significantly increased the likelihood ratio chi-square for prediction of both the composite endpoint (p=0.004) and cardiovascular death (p=0.009). Therefore, MPV may be useful to improve risk stratification in NSTE-ACS patients and should be included in future prospective studies evaluating the role of platelet function in promoting cardiovascular events.

A randomised study comparing the antiplatelet and antiinflammatory effect of clopidogrel 150 mg/day versus 75 mg/day in patients with ST-segment elevation acute myocardial infarction and poor responsiveness to clopidogrel: results from the DOUBLE study.

INTRODUCTION: The antiplatelet effect of standard or increased clopidogrel doses in patients with ST- segment elevation acute myocardial infarction (STEMI) has never been studied. In this study we compared the antiplatelet effect of a 75 mg daily maintenance dose of clopidogrel with 150 mg in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). MATERIALS AND METHODS: Fifty-four patients with STEMI undergoing PCI were randomly allocated to receive either 75 mg/day clopidogrel (group 1) or 150 mg/day (group 2) for 1 month. Platelet function, measured by 5 different assays, was determined at 3 time points: 38+/-8 hours after the procedure, 1 week and 1 month after randomization. RESULTS: In group 1, mean +/- SD platelet reactivity index (PRI) measured with the VASP assay was 57.7+/-15.7% and 46.9+/-15.7% at 1 week and 1 month, respectively, compared to 38.8+/-15.7% and 34.9+/-12.6% in group 2 (p=0.0001). Same results were observed for light transmittance aggregometry, whole blood aggregometry and VerifyNow, but not for thromboelastometry. In contrast to what may be expected, the 75 mg daily maintenance dose took longer than 1-week to provide the full clopidogrel antiplatelet effect. Furthermore, patients in group 2 had a nearly 50% reduction in C-reactive protein levels both at 1 week and 1 month. CONCLUSION: In patients with STEMI and poor responsiveness to clopidogrel a 150 mg daily maintenance dose of clopidogrel is associated with a significant reduction of platelet aggregation and a trend towards reduced inflammation.

A comparison between coronary artery bypass grafting surgery and drug eluting stent for the treatment of unprotected left main coronary artery disease in elderly patients (aged > or =75 years).

AIMS: In this study, we compared the clinical outcomes of elderly patients with unprotected left main coronary artery (ULMCA) stenosis treated with either coronary artery bypass grafting (CABG) or drug-eluting stent (DES). METHODS AND RESULTS: From January 2003 to April 2006, 259 patients with ULMCA stenosis and age > or =75 years underwent coronary revascularization with either CABG or DES. One hundred and sixty-one patients were treated with CABG and 98 with DES. The cumulative unadjusted rates of 2-year mortality were 17% in CABG-treated patients and 18% in those treated with DES (P = 0.71). The adjusted rates of 2-year survival were 85% for CABG-treated patients and 87% for DES-treated patients (P = 0.74). The incidence of 2-year myocardial infarction was 6% in CABG-treated patients and 4% in DES-treated patients (P = 0.11). The incidence of target lesion revascularization (TLR) was 3% in CABG-treated patients and 25% in DES-treated patients (P < 0.0001). In the multivariable analysis, peripheral vascular disease, left ventricular ejection fraction and acute coronary syndrome were independent predictors of 2-year mortality. CONCLUSION: In this study, we could not demonstrate a difference in mortality between CABG-treated patients and those treated with DES. However, the rate of TLR was higher in the DES group.