Prognostic value of divergent pattern detection by 99mTc-sestamibi gated SPECT in patients with anterior acute myocardial infarction.

PURPOSE: In gated myocardial perfusion SPECT, apical remodeling may be identified by the presence of a divergent pattern (DP) of the left ventricle (LV). METHODS AND RESULTS: We examined 150 anterior ST-elevation myocardial infarction (STEMI) patients, all successfully treated with primary percutaneous coronary interventions (PCI). Perfusion gated-SPECT to measure infarct size, LV end-diastolic (ED) and end-systolic (ES) volumes and ejection fraction (EF) was acquired before hospital discharge and repeated at 6-month follow-up. DP was observed in 26 patients, who had larger infarct size (28 ± 19% vs. 15.7 ± 17%, P < 0.02), and lower EF (33 ± 7% vs. 41 ± 10%, P < 0.001) than patients without DP. At follow-up, DP patients had significantly larger EDV (156 ± 54 vs. 107 ± 44 mL, P < 0.0001), ESV (104 ± 47 vs. 59 ± 36 mL, P < 0.0001) and lower EF (35 ± 12% vs. 48 ± 13%, P < 0.0001). 54% of DP patients developed remodeling at follow-up vs. 12% of those without DP (P < 0.001). During follow up, 7 events in the DP group (27%) and 11 events in patients without DP (9%; P < 0.02) occurred. Kaplan-Meier survival curves showed a worse prognosis for DP patients. CONCLUSION: In patients with anterior AMI, early DP detection is related to subsequent LV dysfunction, larger infarct size, and worse severity. It is helpful for predicting LV remodeling at short-term follow-up and has prognostic implications.

Reticulated platelets predict cardiovascular death in acute coronary syndrome patients. Insights from the AMI-Florence 2 Study.

Reticulated platelets (RP) are newly-formed platelets with a greater mass, a residual amount of RNA and an increased prothrombotic potential. No studies investigating the association between RP and the risk of cardiovascular death in acute coronary syndrome (ACS) patients are available. In the frame of the AMI-Florence 2 study, we investigated RP in 229 (154 M/ 75 F) ACS patients (125 ST-elevation myocardial infarction [STEMI]; 104 Non-STEMI/Unstable Angina). RP were measured by using the Sysmex XE-2100 haematology analyzer and were expressed as the percentage of RP out of the total optical platelet count (immature platelet fraction; IPF) and as the percentage of RP highly fluorescent (H-IPF). At one-year follow-up, 22 out of 229 patients (9.6%) died from cardiovascular causes. Higher values of IPF (p=0.05) and H-IPF (p=0.006) were detected in dead compared to alive patients. A receiver operating characteristics curve analysis identified IPF ≥3.3% and H-IPF ≥0.9% as optimal cut-off values to predict cardiovascular death. At the multivariate model adjusted for the Global Registry of Acute Coronary Events (GRACE) risk score, the association between RP and cardiovascular death remained significant for both IPF [OR (95%CI) : 4.15 (1.24-13.91) p=0.02] and H-IPF [OR (95%CI): H-IPF 5.03 (1.38-18.38) p=0.01]. In conclusion, RP are independent predictors of cardiovascular death and may be useful in improving risk stratification for ACS patients. Future prospective studies to evaluate the role of RP in determining cardiovascular events are warranted.

PPARgamma promoter polymorphisms and acute coronary syndrome.

BACKGROUND: PPARgamma (PPARg) is a nuclear transcription factor involved in the control of lipid and glucose homeostasis. Two PPARg common polymorphisms, Pro12Ala and 161C>T, have been found to be associated with cardiovascular disease. In this study, in addition to PPARg coding region, we looked for genetic variations in promoters and their association with acute coronary syndrome (ACS). METHODS: We studied 202 Italian patients with ACS, and 295 healthy Italian subjects by dHPLC (denaturing high-performance liquid chromatography), heteroduplex analysis and direct sequencing or RFLP (restriction fragment length polymorphism) analysis for screening mutations. RESULTS: We identified 7 new and 2 already published polymorphisms in PPARg promoters. The C>T93695 (promoter 4) mutation showed significantly different genotype distribution and allele frequency between controls and ACS patients (p<0.001); the T allele conferred a protection against ACS at both univariate (OR: 0.45, 95% CI 0.29-0.69: p<0.001) and multivariate analysis adjusted for sex, age and traditional cardiovascular risk factors (OR: 0.44, 95% CI 0.25-0.76: p<0.005). Moreover, the 161C>T polymorphism allele frequency (p=0.03) and genotype distribution (p=0.015) resulted to be different in ACS group if compared to healthy controls. CONCLUSIONS: The protective role of 93695C>T polymorphism in PPARg promoter in ACS suggests that PPARg genetic variants may affect the susceptibility to atherosclerotic diseases.

An angiographic evaluation of restenosis rate at a six-month follow-up of patients with ST-elevation myocardial infarction submitted to primary percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is considered to be the optimal type of revascularization in patients with ST-segment elevation myocardial infarction (STEMI). However, the long-term effectiveness of this procedure can be reduced by restenosis. This investigation was aimed at a prospective evaluation, in a group of STEMI patients of "the real world" (not involved in randomised trials), of the angiographic restenosis rate at a 6-month follow-up, and at identifying the relationship between restenosis and the patients' characteristics. MATERIALS AND METHODS: Our study population consisted of 123 patients with STEMI submitted to primary PCI to then undergo stress echocardiography 3 months after PCI and an angiographic evaluation at a 6-month follow-up. RESULTS: a) In real life the restenosis rate is quite high (42.3%); b) no correlation was found between patients' clinical characteristics and restenosis; c) restenosis rate was higher in patients with bare metal stents than in those with drug-eluting stents (55.8% vs. 11.1%; p<0.001); in patients with longer stents (21.6+/-8.62 vs 18.1+/-6.34 mm, p=0.015) and when more than one stent was implanted. Moreover, a consistent number of patients showed restenosis though asymptomatic. CONCLUSIONS: Our data suggest that primary PCI is associated with a high incidence of angiographic restenosis. No correlation was found between patients' clinical characteristics and restenosis. The length and the number of implanted stents seem to be associated with a more probable restenosis at six-month angiographic evaluation. Drug-eluting stent implantation seems to be associated with a lower incidence of restenosis even in STEMI patients.

Different methodologies for evaluating the effect of clopidogrel on platelet function in high-risk coronary artery disease patients.

BACKGROUND: Two point-of-care (POC) systems have been recently proposed as rapid tools with which to evaluate residual platelet reactivity (RPR) in coronary artery disease (CAD) patients. OBJECTIVES AND METHODS: We compared Platelet Function Analyzer-100 (PFA-100) closure times (CTs) by collagen/adenosine 5'-diphosphate (ADP) (C/ADP CT) cartridge and the VerifyNow P2Y12 Assay (VerifyNow) with light transmission aggregation (LTA) induced by 2 and 10 micromol L(-1) ADP in 1267 CAD patients on dual antiplatelet therapy who underwent percutaneous coronary intervention. We also performed the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay by cytofluorimetric analysis in a subgroup of 115 patients. RESULTS: Cut-off values for identifying RPR were: > or = 54% and > or = 66% for LTA induced by 2 and 10 micromol L(-1) ADP respectively, and > or = 264 P2Y12 Reaction Units (PRU) for VerifyNow. The cut-off for PFA-100 C/ADP CT was > or = 68 s. RPR was detected in 25.1% of patients by 2 mumol L(-1) ADP-induced LTA (ADP-LTA), in 23.2% by 10 micromol L(-1) ADP-LTA, in 24.4% by PFA-100, and in 24.7% by VerifyNow. PFA-100 results did not parallel those obtained with LTA. VerifyNow showed a significant correlation (rho = 0.62, P < 0.001) and significant agreement (k = 0.34, P < 0.001) with LTA induced by 2 micromol L(-1) ADP. The correlation was similar but the agreement was better between VerifyNow and 10 micromol L(-1) ADP-LTA (rho = 0.64, P < 0.0001; k = 0.43, P < 0.001). Significant relationships were found between VASP platelet reactivity index and both ADP-LTA and VerifyNow. PFA-100 C/ADP CT did not significantly correlate with any of the other assays. CONCLUSIONS: Our results show a significant correlation between LTA and VerifyNow but not the PFA-100 C/ADP assay. Clinical validation studies for POC systems are necessary.

PAI-1 and homocysteine, but not lipoprotein (a) and thrombophilic polymorphisms, are independently associated with the occurrence of major adverse cardiac events after successful coronary stenting.

OBJECTIVE: To evaluate the role of factor V Leiden, prothrombin G20210A polymorphism, plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism, PAI-1, homocysteine, and lipoprotein (a) (Lp(a)) in the occurrence of major adverse cardiac events (MACE) in patients with acute coronary syndromes who underwent coronary stenting. DESIGN: 520 patients (375 men and 145 women) with acute coronary syndromes and 520 age and sex matched controls were enrolled. MACE were recorded for 109 patients. Heterozygosity for factor V Leiden, prothrombin G20210A polymorphism, and 4G/5G polymorphism did not significantly differ between patients with and without MACE. A significantly higher percentage of patients with increased homocysteine (28% v 19%, p < 0.001) and PAI-1 concentrations (25% v 16%, p < 0.001) had MACE with respect to those who did not. In Kaplan-Meier survival analysis, the overall risk of MACE was significantly higher among patients with increased PAI-1 (p = 0.006) and homocysteine concentrations (p = 0.04). Cox regression analysis adjusted for age, sex, traditional cardiovascular risk factors, renal function, systolic left ventricular function, the number of stenosed vessels, and history of percutaneous coronary intervention or coronary artery bypass grafting showed that homocysteine (odds ratio 7.5, 95% confidence interval (CI) 1.1 to 57.7, p < 0.05) and PAI-1 concentrations (odds ratio 5.3, 95% CI 1.2 to 23.8, p < 0.05) within the fifth quintile (with respect to the first) were significant and independent risk factors for the future occurrence of MACE. CONCLUSIONS: Increased PAI-1 and homocysteine concentrations are independent risk factors for MACE after successful coronary stenting, whereas Lp(a) and thrombophilic polymorphisms are not predictive.

Protein Z plasma levels in different phases of activity of coronary atherosclerosis.

We previously reported that low protein Z plasma levels are associated with acute coronary syndromes (ACS). Aim of the present study was to evaluate protein Z levels in different phases of activity of coronary atherosclerosis. Protein Z plasma levels were measured in 166 (131 male and 35 female) patients consecutively admitted to the University of Florence with a diagnosis of ACS (group A), 166 (131 male and 35 female) patients selected by age and gender in relation to group A from those with a clinical history of ACS who remained symptom- and/or event-free over the last year before the investigation (group B); and 332 (262 male and 70 female) controls comparable for age and gender with the other two groups. None had liver or renal dysfunction nor showed a positivity for antiphospholipid antibodies or for factor V Leiden mutation. Patients under warfarin therapy were excluded. Mean protein Z plasma levels were found to be significantly (P < 0.0001) lower in group A (1475 +/- 684.1 ng mL(-1)) and group B (1327.6 +/- 690.7 ng mL(-1)) as compared with control group (1650.1 +/- 634.5 ng mL(-1)), while no significant differences existed between the two groups of patients (P = 0.06). A logistic regression analysis, performed after the division of the study population into quartiles of protein Z levels and adjusted for all possible confounders, showed a significant increased risk of ACS for the lowest (<1213 ng mL(-1)) as compared with the highest quartile of protein Z in both groups of patients [group A odds ratio (OR): 2.7, 95% CI 1.3-5.5, P = 0.007; group B OR: 3.2, 95% CI 1.1-8.9, P = 0.02). In conclusion, these results strengthen our previous data on low protein Z plasma levels in ACS and indicate a possible dose-response effect of decreasing protein Z plasma levels on the coronary atherosclerotic disease.

Postprocedural PAI-1 activity is a risk marker of subsequent clinical restenosis in patients both with and without stent implantation after elective balloon PTCA.

Stent implantation after balloon dilation of coronary arteries has improved clinical prognosis in patients undergoing transluminal coronary angioplasty (PTCA), but late restenosis remains a relevant problem. A previous study has indicated that PAI-1 activity changes immediately after PTCA without stent implantation are predictive of clinical restenosis. The present study was aimed to investigate the early PAI-1 changes and fibrin formation in patients undergoing elective PTCA with stent implantation. PAI-1 activity and D-dimer plasma levels were evaluated in two groups of patients (G1 underwent only elective balloon PTCA and G2 underwent elective PTCA with stent implantation) before and after the procedure. At the end of the procedure, PAI-1 activity significantly decreased, while D-dimer levels significantly increased in both groups. Post-PTCA D-dimer levels in the group with stent implantation were significantly higher than in the other group (P<.05). In both groups of patients, the post-PTCA PAI-1 activity was higher in patients with subsequent clinical recurrence with restenosis (P<.005 in G1 and P<.0005 in G2) than in those without, whereas no differences were found in D-dimer levels. In conclusion, our results demonstrate that fibrin formation assessed by D-dimer levels is enhanced by stent implantation. However, this behaviour is not related, differently from PAI-1 changes, to subsequent occurrence of clinical restenosis.

Activation of the immune system and coronary artery disease: the role of anti-endothelial cell antibodies.

On the basis of the role of immuno-mediated inflammation in atherosclerosis we investigated, (1) the prevalence of anti-endothelial cell antibodies (AECA) in ischaemic heart disease (IHD); (2) if beta2-glycoprotein I (beta2-GPI) was the target antigen of AECA; (3) the relationship between AECA, tissue factor (TF) and tissue factor pathway inhibitor (TFPI). In 93 consecutive IHD patients undergoing percutaneous transluminal coronary angioplasty (PTCA) and 105 controls AECA were detected by ELISA on human umbilical vein endothelial cells (HUVEC). AECA positive sera were evaluated for anti-beta2-GPI antibodies by ELISA. TF and TFPI plasma levels were assessed by ELISA. Twelve of 93 (12.9%) IHD patients and only one of 105 controls (0.95%) were AECA positive. The prevalence of AECA was higher in unstable angina (UA) than in effort angina (EA) (P=0.01). Three of 12 AECA positive sera resulted positive for anti-beta2-GPI and showed a marked decrease in EC-binding when tested on HUVEC cultured in serum-free medium. The binding was restored by the addition of beta2-GPI. TF and TFPI levels were similar in AECA positive and AECA negative patients. The rate of angiographically documented clinical recurrences was 66.7% in the AECA positive and 14.8% in the AECA negative group (P=0.0004) with a significant relationship between restenosis and AECA (P<0.0001), unchanged by the inclusion of cardiovascular risk factors in the regression model. Our results suggest a 'role' for AECA in the immune-mediated inflammation in UA beta2-GPI is not the only AECA target antigen. AECA are not responsible for high TF and TFPI levels. The high rate of clinical recurrences after PTCA, confirmed by angiography, in AECA positive patients is in line with such a role and suggests further large-scale 'ad hoc' studies.

D-dimer increase after percutaneous transluminal angioplasty and clinical recurrence after primary revascularization in acute myocardial infarction? A pilot study.

It has been reported that the increase of plasminogen activator inhibitor-1 activity immediately after elective coronary angioplasty is related to subsequent clinical recurrence in patients with chronic coronary artery disease. The aims of our study were to evaluate the behavior of plasminogen activator inhibitor-1 and D-Dimer after revascularization in acute myocardial infarction patients treated with angioplasty and stenting and if this behavior is predictive of subsequent clinical recurrence. D-Dimer and plasminogen activator inhibitor-1 activity were evaluated in two groups of patients. Group 1 consisted of 54 consecutive patients undergoing primary angioplasty for acute myocardial infarction and Group 2 consisted of 48 patients undergoing elective angioplasty. Patients underwent control coronary angiography only in the case of clinical recurrence and/or positivity of provocative tests. D-Dimer and plasminogen activator inhibitor-1 baseline levels were significantly higher in group 1 than in group 2 (P<0.0005 and P<0.05, respectively). The percentage of group 1 patients with a post-procedural increase in D-Dimer was significantly higher among those with subsequent clinical recurrence with restenosis (61%) than among those with no recurrence (25%, P<0.05). No difference was observed in group 2. The percentage of group 2 patients in whom no decrease of plasminogen activator inhibitor-1 was observed after angioplasty was significantly higher (83%) among those with subsequent recurrence than among those with no recurrence (38%, P<0.05). This pattern was not observed in group 1. In conclusion, the role of early changes in plasminogen activator inhibitor-1 in predicting clinical recurrence after primary angioplasty in acute myocardial infarction patients is less clear than that observed after elective angioplasty. A significant role seems to be played by a more-marked clotting activation with increased fibrin formation.

Transferring patients for direct coronary angioplasty: a retrospective analysis of 135 unselected patients with acute myocardial infarction.

BACKGROUND: Direct coronary angioplasty (PTCA) represents the most effective treatment for acute myocardial infarction. However, only a minority of patients are initially admitted to hospitals with direct PTCA facilities available 24 hours daily. The safety and benefits of transfer direct PTCA are debated, and we have no data about the early return of patients to the admission hospital. METHODS: We report our experience with transfer direct PTCA in unselected patients with acute myocardial infarction, and the early post-procedural return to the referring hospitals. RESULTS: One hundred and thirty-five unselected patients with acute myocardial infarction were referred to our center for direct PTCA during 1998. The majority of patients (n = 93, 69%, group T) were initially admitted to a primary hospital whereas the rest (n = 42, 31%, group NT) were directly admitted to our hospital. One hundred and thirty-four patients underwent coronary angiography, and direct PTCA was attempted in 126 patients. The median time interval between admission and direct PTCA was higher in group T (60 vs 40 min, p < 0.001). Only 3 patients (3.2%) had severe complications during transfer to our center: 1 patient with cardiogenic shock died, and 2 patients had ventricular fibrillation. The procedural and in-hospital outcomes of both groups were similar. The early post-procedural transfer to the referring hospital was possible in 88% of patients; no complications occurred during the transfer. The incidences of cardiac mortality at 6 months and at long-term follow-up were 3.4 and 5.1% respectively. CONCLUSIONS: In our experience, interhospital transfer for direct PTCA in unselected patients with acute myocardial infarction is feasible and safe. The early return to the admission hospital is safe and does not negatively influence the in-hospital outcome.

Partial anomalous venous return associated with intact atrial septum and persistent left superior vena cava: a case report and literature review.

Left-sided partial anomalous pulmonary venous return (PAPVR) with an intact atrial septum is a rare cardiovascular anomaly. This report deals with the case of a 22-year-old woman who was referred to our Institution because of resting palpitation and exertional dyspnea. Two-dimensional echocardiography revealed right heart volume overload and a dilated coronary sinus. A left-sided PAPVR draining into a persistent left superior vena cava which, in turn, entered a dilated coronary sinus, was correctly detected by magnetic resonance imaging. Diagnosis was confirmed by cardiac catheterization. The literature on this subject is reviewed.

The pre-procedural platelet state predicts clinical recurrence after coronary angioplasty.

Percutaneous transluminal coronary angioplasty is an established therapy for coronary artery disease, but restenosis still occurs at a rate of 25%-40%. The aim of this study was to investigate the acute effect of percutaneous transluminal coronary angioplasty on platelet function and the relationship between platelet function and clinical recurrence. Spontaneous platelet aggregation was assessed before and after successful coronary angioplasty in 155 patients (120 men, 35 women). Patients were followed for a mean time of 20 months; follow-up angiography was performed only in patients with clinical recurrence. In 122 of 155 patients (79%) a significant increase in spontaneous platelet aggregation was observed immediately after coronary angioplasty. Baseline spontaneous platelet aggregation in platelet-rich plasma was significantly lower in patients with clinical recurrence than in those without (P<0.05). Kaplan-Meier event-free survival estimate showed a significant difference in clinical recurrence between patients with spontaneous platelet aggregation in platelet-rich plasma below and above the first quintile (P<0.05) with a relative risk of 2.5. In conclusion. these results indicate that percutaneous transluminal coronary angioplasty enhances spontaneous platelet aggregation and that the platelet state before coronary angioplasty affects the risk of clinical recurrence after the procedure.

Intravenous nitrates in the prehospital management of acute pulmonary edema.

STUDY OBJECTIVE: We sought to assess the effect of nitrates on prehospital mortality among patients with acute pulmonary edema (APE). METHODS: The study involved a retrospective evaluation of the records of prehospital outcome in 640 patients with APE rescued by the mobile CCU (MCCU) of Florence, Italy, between January 1980 and December 1991. The MCCU serves an urban environment with a population of 400,000 in a 102-sq km area. In the years 1980 through 1983, patients were treated with oxygen, morphine, furosemide, digoxin, nitrates, aminophylline, or dopamine, according to the attending physician's judgment. From 1984 through 1991, new guidelines for the use of intravenous nitrates, based on differential treatment according to blood pressure, were in use. RESULTS: Overall prehospital mortality rate for APE in all patients was 7.8% (50 of of 640 patients). Mortality after 1984 was significantly lower than before (5.3% versus 13%, P < .01). Nitrates were effective in reducing mortality, even in hypotensive patients. Multivariate analysis showed that outcome was significantly affected by two clinical features (dyspnea and low blood pressure), treatment with nitrates, and calendar period effects (before/after 1984). CONCLUSION: Our findings suggest that the use of intravenous nitrates improves short-term prognosis in APE.

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 angioplasty (PTCA). All patients had single-vessel coronary artery disease (only one > or = 85% stenosis in a major coronary artery) and normal left ventricular function. All 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.