Timing of Oral P2Y12 Inhibitor Administration in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Although oral P2Y12 inhibitors are key in the management of patients with non-ST-segment elevation acute coronary syndrome, the optimal timing of their administration is not well defined. OBJECTIVES: The purpose of this study was to compare downstream and upstream oral P2Y12 inhibitors administration strategies in patients with non-ST-segment elevation acute coronary syndrome undergoing invasive treatment. METHODS: We performed a randomized, adaptive, open-label, multicenter clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was the superiority of the downstream versus the upstream strategy on the combination of efficacy and safety events (net clinical benefit). RESULTS: We randomized 1,449 patients to downstream or upstream oral P2Y12 inhibitor administration. A pre-specified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint, a composite of death due to vascular causes; nonfatal myocardial infarction or nonfatal stroke; and Bleeding Academic Research Consortium type 3, 4, and 5 bleeding through day 30, did not differ significantly between the downstream and upstream groups (percent absolute risk reduction: -0.46; 95% repeated confidence interval: -2.90 to 1.90). These results were confirmed among patients undergoing percutaneous coronary intervention (72% of population) and regardless of the timing of coronary angiography (within or after 24 h from enrollment). CONCLUSIONS: Downstream and upstream oral P2Y12 inhibitor administration strategies were associated with low incidence of ischemic and bleeding events and minimal numeric difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of 1 strategy over the other. (Downstream Versus Upstream Strategy for the Administration of P2Y12 Receptor Blockers In Non-ST Elevated Acute Coronary Syndromes With Initial Invasive Indication [DUBIUS]; NCT02618837).

Impact of sex on comparative outcomes of bivalirudin versus unfractionated heparin in patients with acute coronary syndromes undergoing invasive management: a pre-specified analysis of the MATRIX trial.

AIMS: Our aim was to assess whether bivalirudin compared with unfractionated heparin (UFH) is associated with consistent outcomes in males and females with acute coronary syndrome (ACS) undergoing invasive management. METHODS AND RESULTS: In the MATRIX programme, 7,213 patients were randomised to bivalirudin or UFH. Patients in the bivalirudin group were subsequently randomly assigned to receive or not a post-PCI bivalirudin infusion. The 30-day co-primary outcomes were major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or stroke, and net adverse clinical events (NACE), defined as MACE or major bleeding. The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target vessel revascularisation (TVR), definite stent thrombosis (ST), or NACE. The rate of MACE was not significantly lower with bivalirudin than with heparin in male (rate ratio [RR] 0.90, 95% confidence interval [CI]: 0.75-1.07; p=0.22) and female patients (RR 1.06, 95% CI: 0.80-1.40; p=0.67) without significant interaction (pint=0.31), nor was the rate of NACE (males: RR 0.85, 95% CI: 0.72-1.01; p=0.07; females: RR 0.98, 95% CI: 0.76-1.28; p=0.91; pint=0.38). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent TVR, definite ST, or NACE (males: RR 0.84, 95% CI: 0.66-1.07; p=0.15; females: RR 1.06, 95% CI: 0.74-1.53; p=0.74; pint=0.28). CONCLUSIONS: In ACS patients, the rates of MACE and NACE were not significantly lower with bivalirudin than with UFH in both sexes. The rate of the composite of urgent TVR, definite ST, or NACE was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion in both sexes.

Acute Kidney Injury After Radial or Femoral Access for Invasive Acute Coronary Syndrome Management: AKI-MATRIX.

BACKGROUND: It remains unclear whether radial access (RA), compared with femoral access (FA), mitigates the risk of acute kidney injury (AKI). OBJECTIVES: The authors assessed the incidence of AKI in patients with acute coronary syndrome (ACS) enrolled in the MATRIX-Access (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial. METHODS: Among 8,404 patients, 194 (2.3%) were excluded due to missing creatinine values, no or an incomplete coronary angiogram, or previous dialysis. The primary AKI-MATRIX endpoint was AKI, defined as an absolute (>0.5 mg/dl) or a relative (>25%) increase in serum creatinine (sCr). RESULTS: AKI occurred in 634 patients (15.4%) with RA and 712 patients (17.4%) with FA (odds ratio [OR]: 0.87; 95% confidence interval [CI]: 0.77 to 0.98; p = 0.0181). A >25% sCr increase was noted in 633 patients (15.4%) with RA and 710 patients (17.3%) with FA (OR: 0.87; 95% CI: 0.77 to 0.98; p = 0.0195), whereas a >0.5 mg/dl absolute sCr increase occurred in 175 patients (4.3%) with RA versus 223 patients (5.4%) with FA (OR: 0.77; 95% CI: 0.63 to 0.95; p = 0.0131). By implementing the Kidney Disease Improving Global Outcomes criteria, AKI was 3-fold less prevalent and trended lower with RA (OR: 0.85; 95% CI: 0.70 to 1.03; p = 0.090), with stage 3 AKI occurring in 28 patients (0.68%) with RA versus 46 patients (1.12%) with FA (p = 0.0367). Post-intervention dialysis was needed in 6 patients (0.15%) with RA and 14 patients (0.34%) with FA (p = 0.0814). Stratified analyses suggested greater benefit with RA than FA in patients at greater risk for AKI. CONCLUSIONS: In ACS patients who underwent invasive management, RA was associated with a reduced risk of AKI compared with FA. (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627).

One-year follow-up of patients treated with new-generation polymer-based 38 mm everolimus-eluting stent: the P38 study.

OBJECTIVES: To assess the clinical outcome at 1-year follow-up of real-world patients with long coronary lesions treated with the 38 mm Xience Prime (Abbott Vascular) everolimus-eluting stent (EES). BACKGROUND: Long-lesions present special challenges to the interventional cardiologists, including increased risk of restenosis, periprocedural injury, geographical miss, and stent deliverability. Indeed, results obtained with shorter stent in the treatment of simpler lesions are of limited applicability to longer stents. METHODS: Consecutive patients presenting with a long coronary lesion treated by percutaneous coronary intervention with at least one implanted 38 mm EES were enrolled in the study. Their clinical data were prospectively registered. Major adverse cardiac events (MACE) were defined as a composite of cardiac death, nonfatal myocardial infarction (according to the Universal Definition) and target vessel revascularization. Stent thrombosis was defined according to the Academic Research Consortium criteria. RESULTS: Overall, 203 real-world patients (152 men, 68 ± 9 years) were enrolled in the P38 Study. At 1-year follow-up, 6 (3.0%) patients had died from cardiac causes, 7 (3.4%) had a nonfatal myocardial infarction and 8 (3.9%) underwent target vessel revascularization, yielding a 10.3% cumulative rate of MACE. Two patients had a stent thrombosis (one definite and one probable). No significant differences in event rates were found between patients with and without an additional stent implanted overlapping the 38 mm one. CONCLUSIONS: The use of a new-generation polymer-based 38 mm EES in a real-world population with unselected long lesions is associated with excellent procedural results and good clinical outcomes at 12-month follow-up.

Comparison of risk of acute kidney injury after primary percutaneous coronary interventions with the transradial approach versus the transfemoral approach (from the PRIPITENA urban registry).

The risk of acute kidney injury (AKI) is a major issue after percutaneous coronary interventions (PCIs), especially in the setting of ST-elevation myocardial infarction. Preliminary data from large retrospective registries seem to show a reduction of AKI when a transradial (TR) approach for PCI is adopted. Little is known about the relation between vascular access and AKI after emergent PCI. We here report the results of the Primary PCI from Tevere to Navigli (PRIPITENA), a retrospective database of primary PCI performed at high-volume centers in the urban areas of Rome and Milan. Primary end point of this study was the occurrence of AKI in the TR and transfemoral (TF) access site groups. Secondary end points were major adverse cardiovascular events, stent thrombosis, and Thrombolysis in Myocardial Infarction major and minor bleedings. The database included 1,330 patients, 836 treated with a TR and 494 with a TF approach. After a propensity-matched analysis performed to exclude possible confounders, we identified 450 matched patients (225 TR and 225 TF). The incidence of AKI in the 2 matched groups was lower in patients treated with TR primary PCI (8.4% vs 16.9%, p = 0.007). Major adverse cardiovascular events and stent thrombosis were not different among study groups, whereas major bleedings were more often seen in the TF group. At multivariate analysis, femoral access was an independent predictor of AKI (odds ratio 1.654, 95% confidence interval 1.084 to 2.524, p = 0.042). In conclusion, in this database of primary PCI, the risk of AKI was lower with a TR approach, and the TF approach was an independent predictor for the occurrence of this complication.

Bivalirudin or heparin in primary angioplasty performed through the transradial approach: results from a multicentre registry.

BACKGROUND: Data on the effect of bivalirudin therapy in primary percutaneous coronary interventions (PCI) performed through the transradial approach are limited. The aim of our study was to evaluate bleeding complications and clinical outcomes in primary PCI performed through the transradial approach with bivalirudin therapy. METHODS: We retrospectively evaluated primary PCI performed through the transradial approach from January 2008 to June 2013. Patients were divided in two groups according to the use (group 1) or not (group 2) of bivalirudin. The primary end points were major bleedings and major adverse cardiac events (MACE) within 30 days. RESULTS: During the 5 years analysed, 1009 patients underwent primary PCI through the transradial approach: 154 patients were treated with bivalirudin (males 79%, age 65 ± 14 years) and 855 with heparin (males 82%, 63 ± 12 years). In group 1, the use of glycoprotein IIb/IIIa inhibitors was only 4%, compared to 55% (p<0.001) in group 2. There were no significant differences between the two groups for major bleedings (0.65% in group 1 and 1.17% in group 2, p=0.88) nor for minor bleedings (1.3% in group 1 and 1.5% in group 2, p=0.83). There were also no significant differences in MACE (7.1% in group 1 and 10.4% in group 2, p=0.27). The 30-day mortality rate was 3.9% in group 1 and 5.4% in group 2 (p=0.56). CONCLUSIONS: In this registry of primary PCI performed through the transradial approach, bivalirudin was not associated with a significant reduction in major bleeding or MACE compared to heparin and provisional glycoprotein IIb/IIIa inhibitors.

Case-control registry of excimer laser coronary angioplasty versus distal protection devices in patients with acute coronary syndromes due to saphenous vein graft disease.

Laser atherectomy might decrease procedural complications during percutaneous coronary intervention (PCI) of degenerated saphenous vein grafts (SVGs) in case of unstable or thrombotic lesions because of its ability to debulk and vaporize thrombus. We aimed at prospectively evaluating the safety and efficacy of excimer laser coronary angioplasty (ELCA) as a primary treatment strategy in consecutively unstable patients undergoing PCI of degenerated SVG lesions. Seventy-one consecutive patients with non-ST elevation acute coronary syndrome (mean age 69 ± 10 years, 66 men [89%]) undergoing PCI of degenerated SVG were enrolled in a prospective case-control registry, using 2 different distal protection devices (DPDs; FilterWire EZ [Boston Scientific, Natick, Massachusetts; n = 24] and SpiderRX [Ev3, Plymouth, Minnesota; n = 23]) or ELCA (n = 24). Primary end points of the study were incidence of angiographic microvascular obstruction (Thrombolysis In Myocardial Infarction flow grade of <3 or Thrombolysis In Myocardial Infraction flow grade of 3 with myocardial blush grade 1 to 2) and incidence of type IVa myocardial infarction. Angiographic microvascular obstruction incidence tended to be less in ELCA-treated patients compared with DPD-treated patients (3 [13%] vs 15 [32%], p = 0.09). Type IVa myocardial infarction incidence was more in DPD-treated patients compared with ELCA-treated patients (23 [49%] vs 5 [21%], p = 0.04). In conclusion, in patients with non-ST elevation acute coronary syndrome undergoing PCI of degenerated SVG, ELCA compared with DPD, is associated with a trend for better myocardial reperfusion and a lesser incidence of periprocedural necrosis. Controlled randomized trials are warranted to confirm these early observations.

Five-year outcomes in patients with chronic total coronary occlusion treated with drug-eluting vs bare-metal stents: a case-control study.

BACKGROUND: Limited data exist on long-term safety and effectiveness of drug-eluting stents (DESs) in true chronic total coronary occlusion (CTO) settings. We evaluated 5-year clinical outcomes of patients with CTO treated successfully with DES vs bare-metal stent (BMS). METHODS: We compared the 5-year clinical outcomes of 156 patients treated with DES implantation with outcomes of a historical cohort of 159 patients treated with BMS. Primary end point was freedom from major adverse cardiac events (MACEs; defined as death, myocardial infarction [MI], and target lesion revascularization [TLR]); secondary end points were freedom from target vessel failure (TVF; combination of target vessel revascularization, MI, and cardiac death) and TLR at 5 years. RESULTS: After 5 years, the DES group had significantly superior event-free survival from MACE (84% vs 69%; log rank P < 0.001), TVF (71% vs 84%; P = 0.002), and TLR (77% vs 92%; P = 0.0001), compared with the BMS group. The Cox proportional hazards model identified BMS vs DES (adjusted hazard ratio [HR] = 3.37; 95% confidence interval [CI], 1.85-6.17; P = 0.001), final minimal lumen diameter (HR, 0.27; 95% CI, 0.14-0.52; P = 0.0001), and stent length (HR, 1.01; 95% CI, 1.00-1.03; P = 0.03) as independent predictors of MACE at 5-year follow-up. Twelve (7%) and 7 (4%) stent thromboses occurred in the DES and BMS groups (P = 0.23), respectively. CONCLUSIONS: After 5 years, DESs were superior to BMSs in reducing MACE, TVF, and TLR in patients with CTO and should be the preferred strategy.

Serum levels of γ-glutamyltransferase and progression of coronary atherosclerosis.

BACKGROUND: Progression of coronary atherosclerosis (ATS) has clinical implications. Serum levels of γ-glutamyltransferase (GGT), a marker of oxidative stress, predict the risk of cardiovascular events. However, the role of GGT levels in the progression of coronary ATS has never been established. MATERIALS AND METHODS: Consecutive patients undergoing two coronary angiographies (CAs) separated by at least 6 months were prospectively enrolled between May 2008 and June 2010. All patients were discharged on statins after the first CA. The severity and extent of coronary ATS were graded according to Bogaty's score, and the variation (Δ) in stenosis score and extent index between follow-up (S2 and E2) and basal values (S1 and E1) were calculated. Predictors of ΔS2-1 and ΔE2-1 were assessed among clinical and laboratory data, including GGT levels, analyzed as Δ between follow-up and basal values (ΔGGT2-1). RESULTS: We enrolled 100 consecutive patients (age 64±11 years, 68% men). Compliance with statin therapy was 100%. At multiple regression analysis, ΔGGT2-1 was the only independent predictor of ΔS2-1 (B=0.18, SE=0.07, P=0.05), with Δlow-density lipoprotein-cholesterol2-1 levels being of borderline statistical significance (P=0.07). On multiple regression analysis, ΔGGT2-1 was the only independent predictor of ΔE2-1 (B=0.32; SE=0.11; P=0.04), with active smoking habit and Δfibrinogen2-1 levels being of borderline statistical significance (P=0.08 and 0.06, respectively). CONCLUSION: ΔGGT2-1 is associated with angiographic coronary ATS progression in patients with ischemic heart disease on statin treatment, suggesting that oxidative stress may be another therapeutic target for preventing ATS progression beyond that of lipid-lowering therapies.

Late (3 years) follow-up of successful versus unsuccessful revascularization in chronic total coronary occlusions treated by drug eluting stent.

The success rate of recanalization of coronary chronic total occlusion (CTO) has improved in recent years, but the clinical benefit associated with successful CTO recanalization in the drug-eluting stent (DES) era is not well known. A cohort of 317 consecutive patients (mean age 65 ± 10, 84% men) with CTOs (defined as Thrombolysis In Myocardial Infarction [TIMI] flow grade 0 and duration >3 months) of native coronary vessels in which percutaneous coronary intervention was attempted was enrolled from June 2005 to March 2009. All successful procedures (196 patients) were performed by DES implantation. The incidence of major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, and repeat revascularization) was assessed during a mean follow-up period of 3 years. MACE predictors were assessed in clinical, angiographic, and procedural data, including procedural success. Patients with successful percutaneous coronary intervention experienced a significantly lower MACE rate compared to those with failed procedures (17 [9%] vs 32 [26%], p = 0.008). Patients with multivessel disease experienced MACEs more frequently than those with single-vessel disease (45 [22%] vs 4 [4%], p = 0.002). On multiple Cox regression analysis, the presence of multivessel disease and CTO opening failure were independent predictors of MACEs (hazard ratio 2.31, 95% confidence interval 1.17 to 4.96, p = 0.01, and hazard ratio 1.81, 95% confidence interval 1.33 to 4.12, p = 0.02, respectively). The worst prognosis was confined to patients with multivessel disease and failed procedures (hazard ratio 2.73, 95% confidence interval 1.21 to 3.92, p = 0.03). In conclusion, successful recanalization of CTOs with DES translates into a reduction of the 3-year MACE rate compared to failed procedures, and the worst prognosis is observed in patients with failed procedures and multivessel disease, a notion that might be taken into account in the management of patients with coronary CTOs.

Filter no-reflow during percutaneous coronary intervention of saphenous vein grafts: incidence, predictors and effect of the type of protection device.

AIMS: To assess the main predictors and significance of filter no-reflow (FNR) in protected saphenous vein graft (SVG) percutaneous coronary intervention (PCI) and the effect of two different filter-based devices on FNR incidence. The phenomenon of FNR has been described as a transient impairment of blood flow due to debris plugging of a filter-based device used to shield the distal microvasculature during SVG PCI. METHODS AND RESULTS: Fifty consecutive patients treated with SVG PCI were enrolled, using two different filter-based devices (FilterWire EZ™ [Boston Scientific, Natick, MA, USA] and SpiderRX® [Ev3, Plymouth, MN, USA]). We evaluated: 1) the value of clinical and angiographic variables for predicting FNR including the recently-described "degeneration score" (DS); 2) the predictive value of FNR for post-procedural (type IVa) myocardial infarction (MI); 3) the effect of filter type on incidence of FNR. FNR was observed in 30% of patients and was predicted by a higher DS at baseline (2.1±0.9 vs. 1.4±0.8, p=0.02, respectively) as well as by the type of filter used (54% vs. 23% in SpiderFX and FilterWire EZ, respectively, p=0.04). However, at multivariate analysis DS was the only independent predictor of FNR (OR 2.47, CI 95% 1.06-5.76, p=0.04). Graft age and FNR were found to be independent predictors of type IVa MI (OR 1.28; CI%E2%80%AF95% 1.01-1.64, p=0.04 and OR 15.69; CI%E2%80%AF95% 2.12-116.39, p=0.007, respectively). CONCLUSIONS: FNR is a common complication of protected SVG stenting. FNR occurs mainly in grafts with a high degeneration score, and the presence of FNR predicts post-procedural myocardial infarction.

Eosinophil cationic protein and clinical outcome after bare metal stent implantation.

OBJECTIVE: we assessed the association between baseline eosinophil cationic protein (ECP) levels, a sensitive marker of eosinophil activation, and clinical outcome in patients undergoing bare metal stent (BMS) implantation. METHODS: basal ECP levels were measured in 110 patients (69±11 years, 88 men) undergoing BMS implantation. Major adverse cardiac events (MACEs), defined as cardiac death, non-fatal myocardial infarction, or clinically-driven target lesion revascularization, were registered at 24-month follow-up. RESULTS: eighteen (16.4%) patients had MACEs and showed higher ECP levels compared with those without MACEs [20.1 (9.8-47.3) vs. 9.5 (5.0-27.2) g/L, p=0.02]. At follow-up, ECP level>11 g/L was the only significant predictor of MACEs (HR 3.5, 95% CI 1.1-10.4, p=0.03). CONCLUSION: basal ECP levels are associated with MACEs after BMS implantation, suggesting that an allergic-mediated inflammation against the metal could explain some adverse reactions occurring after coronary stenting.

A case of myocardial infarction effectively treated by emergency coronary stenting soon after a Bentall-De Bono aortic surgery.

Postoperative ischemia may complicate cardiac surgery, despite myocardial protection and recent technical developments. Its medical management in the intensive cardiac care unit is usually efficient, although sometimes it requires the revision of the surgical site. In other cases, urgent coronary angiography and subsequent coronary stenting may resolve the situation. Ostial stenosis of coronary anastomoses is a well-known uncommon but dramatic complication after aortic surgery causing myocardial ischemia. Cases of effort angina have been described several months after surgery, but in some cases, acute myocardial infarction may occur days or weeks after intervention. We here describe an anteroseptal ST-elevation myocardial infarction soon after a Bentall aortic root replacement due to compression of the left main ostium by surgical glue, which has been effectively treated by emergency coronary stenting. This case highlights the importance of a joint management of acute myocardial ischemia after cardiac surgery by the cardiac surgeon and the interventional cardiologist.

Angiographic predictors of recurrent stent thrombosis (from the Outcome of PCI for stent-ThrombosIs MultIcentre STudy [OPTIMIST]).

Stent thrombosis is a catastrophic occurrence burdened by a high mortality rate and a tendency to recur. We sought to evaluate the angiographic risk factors for recurrent stent thrombosis (rST) in a subpopulation of 91 Outcome of PCI for stent-ThrombosIs Multicenter STudy (OPTIMIST) patients who underwent quantitative angiographic evaluation by an independent core laboratory. The Academic Research Consortium criteria were used for rST adjudication. A multivariate Cox proportional hazards model was applied to estimate the hazard ratios and the corresponding 95% confidence intervals for the occurrence of Academic Research Consortium-defined, definite rST (primary end point), definite or probable rST (secondary end point), and definite or probable or possible rST (secondary end point). A total of 8 definite rST events occurred during a median follow-up of 244 days (range 165 to 396), of which 5 were early and 3 were late. In the multivariate model, a residual thrombus score of > or =3 (hazard ratio 6.5, 95% confidence interval 1.4 to 30.7, p = 0.017) and a larger postprocedural reference vessel diameter (hazard ratio 4.5, 95% confidence interval 1.5 to 13.3, p = 0.006) were significantly associated with the primary end point. When the same model was applied to the 15 definite and probable rST events, only a residual thrombus score of > or =3 (hazard ratio 7.8, 95% confidence interval 2.5 to 24.5, p <0.001) was significantly associated with rST. Finally, when possible rST events were included (18 patients), a residual thrombus score of > or =3 remained associated with the dependent variable (hazard ratio 6.1, 95% confidence interval 2.0 to 18.2, p = 0.001), along with a larger postprocedural reference vessel diameter. In conclusion, when performing percutaneous coronary intervention for stent thrombosis, the residual thrombus burden and larger reference vessel were potent risk factors for rST.

Eosinophil cationic protein: A new biomarker of coronary atherosclerosis.

AIMS: Coronary atherosclerosis is a chronic inflammatory disease, but different inflammatory biomarkers may reflect different phases of atherosclerotic plaque evolution. We aimed at assessing the role of eosinophil cationic protein (ECP), a sensitive marker of eosinophil activation, and C-reactive protein (CRP) in coronary artery disease (CAD). METHODS AND RESULTS: Consecutive anginal patients with angiographic evidence of CAD [stable angina (SA) or non-ST-elevation acute coronary syndrome (NSTE-ACS)], or with angiographically normal coronary arteries (NCA) were enrolled. The severity of CAD was graded according to Bogaty's score and coronary lesion morphology was defined as smooth or complex. Baseline ECP and high sensitivity CRP were measured in all patients. Of 198 patients (64 + or - 10 years, male 74%), 91 had SA, 57 had NSTE-ACS and 50 had NCA. ECP levels were significantly higher in SA [30 microg/L (13.8-46.9), p<0.001] and NSTE-ACS [21.8 microg/L (5.5-46.3), p=0.016] compared to NCA [9.7 microg/L (6.1-13.6)], without significant difference between SA and NSTE-ACS (p=0.45). CRP levels were significantly higher in NSTE-ACS [2.38 mg/L (1.11-11.94)] compared to SA [1.48 mg/L (0.82-2.83), p=0.03], and NCA [1.09 mg/L (0.8-2.1), p<0.001], without significant difference between SA and NCA (p=0.20). The addition of ECP to main cardiovascular risk factors improved the area under the curve from 0.88 to 0.92, p=0.007 for the angiographic diagnosis of CAD; further addition of CRP increased the area to 0.94, p=0.014. At multiple linear regression analysis ECP levels independently predicted CAD severity (p=0.001), whereas CRP levels independently predicted lesion complexity (p=0.01). CONCLUSIONS: Our study shows that ECP is a marker of CAD and that different inflammatory biomarkers reflect different phases of atherosclerotic plaque evolution.

Pre-intervention eosinophil cationic protein serum levels predict clinical outcomes following implantation of drug-eluting stents.

AIMS: Eosinophils have been identified in post-mortem studies as important players of both restenosis and thrombosis after drug-eluting stent (DES) implantation. We aimed at assessing the association between baseline levels of eosinophil cationic protein (ECP), a marker of eosinophil activation, and recurrence of clinical events in a consecutive series of patients who underwent DES implantation. METHODS AND RESULTS: Two hundred patients (age 63 +/- 10.4, males 75%) undergoing implantation of first-generation DES (Taxus or Cypher stents) were enrolled. We measured serum levels of ECP and total IgE by enzyme-linked immunosorbent assay and of C-reactive protein by high-sensitivity nephelometry prior to percutaneous coronary intervention. A clinical follow-up was planned 18 months after discharge. Major adverse cardiac events (MACEs), such as cardiac death, recurrent myocardial infarction, or clinically driven target lesion revascularization, were the endpoint of the study. Twenty-two patients (11%) had MACEs and showed higher serum levels of ECP compared with those without MACEs [30.5 (14.4-50) vs. 12.2 (4.4-31) microg/L, P = 0.004]. At simple Cox regression analysis, serum levels of ECP were a significant predictor of MACEs (hazard ratio 1.016, 95% confidence interval 1.003-1.03, P = 0.018). CONCLUSION: This study shows for the first time an association between baseline ECP levels and the occurrence of MACEs in patients undergoing implantation of DES. Further studies are warranted to establish whether in this setting ECP is a risk marker or plays a contributory pathogenetic role.

Angiographic and clinical outcome of invasively managed patients with thrombosed coronary bare metal or drug-eluting stents: the OPTIMIST study.

AIMS: Stent thrombosis (ST) is a major complication of percutaneous coronary interventions (PCIs). An invasive management by re-PCI is the commonly adopted treatment for ST, but data on outcome are limited. METHODS AND RESULTS: We performed a 2-year multicentre registry enrolling consecutive patients with angiographically confirmed ST undergoing PCI. The primary angiographic endpoint was optimal angiographic reperfusion (TIMI 3 + blush grade 2 or 3). The primary clinical endpoints were death and major adverse coronary and cerebrovascular events (MACCEs) at 6 months. A total of 110 patients underwent 117 urgent PCI during the study. Patients with drug-eluting stent (DES) thrombosis, compared with those with bare metal stent (BMS) thrombosis, exhibited a higher rate of late or very late presentation and of anti-platelet therapy withdrawal. Optimal angiographic reperfusion was obtained in 64% of the patients. Death and MACCE rates at 6 months were 17 and 30%, respectively. Clinical outcome was similar for BMS and DES thrombosis. Very late ST, implantation of stent during PCI for ST, and failure to achieve optimal angiographic reperfusion were the independent predictors of 6-month mortality. CONCLUSION: DES and BMS thromboses have different clinical features, but a similar poor outcome. Indeed, PCI for ST is associated with a low rate of reperfusion and to a high rate of death and MACCE, calling for action in order to prevent its occurrence and to improve its management.

Predictive value of preintervention C-reactive protein on clinical outcome after directional coronary atherectomy followed by stent implantation.

BACKGROUND: Preprocedural C-reactive protein (CRP) serum levels have been shown to predict the recurrence of angina or major adverse cardiac events after percutaneous coronary intervention. Directional coronary atherectomy (DCA), by reducing residual plaque burden and restenosis, has been shown to improve clinical outcome after coronary stenting. Thus, we assessed the influence of preprocedural CRP serum levels on the recurrence of cardiac events after DCA followed by bare metal stent implantation. METHODS: We enrolled 40 consecutive patients (34 males; 61+/-10 years old) with single-vessel disease who were undergoing DCA. In all patients, preprocedural CRP serum levels were measured by an ultrasensitive nephelometric method. The endpoint of the study was defined as the composite incidence of death, myocardial infarction, and recurrence of angina requiring repeat revascularization at 6-month follow-up. RESULTS: CRP serum levels were a significant independent predictor of the composite endpoint at multiple regression analysis [odds ratio=1.69; 95% confidence interval (95% CI)=1.04-2.75; P=.033]. Patients with recurrence of cardiac events had CRP serum levels higher than those of patients not having events on follow-up [3.95 (2.2-5.7) vs. 2 (1.3-3.3); P=.05]. CONCLUSION: In conclusion, our study shows that baseline CRP serum levels predict cardiac events after coronary bare metal stenting despite plaque debulking with directional atherectomy.

The Outcome of PCI for stent-ThrombosIs MultIcentre Study (OPTIMIST): rationale and design of a multicenter registry.

BACKGROUND: Stent thrombosis (ST) is a recognized complication limiting the clinical efficacy of percutaneous coronary interventions (PCI). Because of the increasing number of stent-based PCI, the absolute number of patients experiencing ST is expected to expand. Re-PCI is the commonly adopted treatment for patients with ST; however, the prognostic variables as well as the angiographic and clinical results have not been systematically assessed. Moreover, the possible benefit associated with the use of adjunctive devices (AD) with theoretical antiembolic property has not been systematically analyzed in this high-risk population. METHODS: We present the design of a prospective and retrospective multicenter registry to assess the contemporary angiographic and clinical outcome of PCI in patients with ST. Moreover, we sought to assess if the use of thrombectomy or distal protection AD is associated with any improvement in the PCI's angiographic results. All patients with angiographically confirmed ST undergoing attempt of PCI in the enrolling centers during a fixed 2-year study period will enter the study. Clinical outcome during hospitalization, at 30 days and 6 months will be assessed. Percutaneous coronary intervention with or without AD will be performed according to physician's discretion. All PCI cine-film will undergo blind core laboratory analysis to assess a series of key angiographic data (TIMI flow, TIMI frame count, thrombus score, myocardial blush grade, distal embolization). CONCLUSIONS: The OPTIMIST study is designed to provide a detailed description of the angiographic and clinical outcome achieved in the real world with contemporary PCI for ST. Moreover, it will provide observational data regarding the role of AD in this high-risk scenario.