Data on administration of cyclosporine, nicorandil, metoprolol on reperfusion related outcomes in ST-segment Elevation Myocardial Infarction treated with percutaneous coronary intervention.

Mortality and morbidity in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) are still high [1]. A huge amount of the myocardial damage is related to the mitochondrial events happening during reperfusion [2]. Several drugs directly and indirectly targeting mitochondria have been administered at the time of the PCI and their effect on fatal (all-cause mortality, cardiovascular (CV) death) and non fatal (hospital readmission for heart failure (HF)) outcomes have been tested showing conflicting results [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. Data from 15 trials have been pooled with the aim to analyze the effect of drug administration versus placebo on outcome [17]. Subgroup analysis are here analyzed: considering only randomized clinical trial (RCT) on cyclosporine or nicorandil [3], [4], [5], [9], [10], [11], excluding a trial on metoprolol [12] and comparing trial with follow-up length <12 months versus those with longer follow-up [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. This article describes data related article titled "Clinical Benefit of Drugs Targeting Mitochondrial Function as an Adjunct to Reperfusion in ST-segment Elevation Myocardial Infarction: a Meta-Analysis of Randomized Clinical Trials" [17].

Clinical benefit of drugs targeting mitochondrial function as an adjunct to reperfusion in ST-segment elevation myocardial infarction: A meta-analysis of randomized clinical trials.

AIMS: To perform a systematic review and meta-analysis of randomized clinical trials (RCT) comparing the effectiveness of drugs targeting mitochondrial function vs. placebo in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical coronary reperfusion. METHODS: Inclusion criteria: RCTs enrolling STEMI patients treated with primary percutaneous coronary intervention (PCI) and comparing drugs targeting mitochondrial function vs. placebo. Odds ratios (OR) were computed from individual studies and pooled with random-effect meta-analysis. RESULTS: Fifteen studies were identified involving 5680 patients. When compared with placebo, drugs targeting mitochondrial component/pathway were not associated with significant reduction of cardiovascular and all-cause mortality (OR 0.9, 95% CI 0.7-1.17 and OR 0.92, 95% CI 0.69-1.23, respectively). However, these agents significantly reduced hospital admission for heart failure (HF) (OR 0.64; 95% CI 0.45-0.92) and increased left ventricular ejection fraction (LVEF) (OR 1.44; 95% CI 1.15-1.82). After analysis for subgroups according to the mechanism of action, drugs with direct/selective action did not reduce any outcome. Conversely, those with indirect/unspecific action showed a significant effect on cardiovascular mortality (0.65, 95% CI 0.46-0.92), all-cause mortality (OR 0.69, 95% CI 0.52-0.92), hospital readmission for HF (OR 0.41, 95% CI 0.28-0.6) and LVEF (OR 1.49, 95% CI 1.09-2.05). CONCLUSIONS: Administration of drugs targeting mitochondrial function in STEMI patients undergoing primary PCI appear to have no effect on mortality, but may reduce hospital readmission for HF. The drugs with a broad-spectrum mechanism of action seem to be more effective in reducing adverse events.

Early changes of left ventricular filling pattern after reperfused ST-elevation myocardial infarction and doxycycline therapy: Insights from the TIPTOP trial.

AIM: Metalloproteinases inhibition by doxycycline reduces cardiac protein degradation at extracellular and intracellular level in the experimental model ischemia/reperfusion injury. Since both extracellular cardiac matrix and titin filaments inside the cardiomyocyte are responsible for the myocardial stiffness, we hypothesized that doxycycline could favorably act on left ventricular (LV) filling pressures in patients after reperfused acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Seventy-three of 110 patients of the TIPTOP trial underwent a 2D-Echo-Doppler on admission, and at pre-discharge and at 6-month after a primary PCI for STEMI and LV dysfunction. From admission to pre-discharge, LV filling changed from a high filling pressure (HFP) to a normal filling pressure (NFP) pattern in 91% of the doxycycline-group, and in 67% of the control-group. Conversely, 1% of the doxycycline-group, and 37% of the control-group changed the LV filling from NFP to HFP pattern. Overall, a pre-discharge HFP pattern was present in 4 patients (11%) of the doxycycline-group and in 13 patients (36%) of the control-group (p=0.025). The evaluation of metalloproteinases and their tissue inhibitors plasma concentrations provide possible favorable action of doxycycline. On the multivariate analyses, troponine I peak (p=0.026), doxycycline (p=0.033), and on admission to pre-discharge LVEF changes (p=0.044) were found to be associated with pre-discharge HFP pattern. Independently of their baseline LV filling behavior, the 6-month remodeling was less in patients with pre-discharge NFP pattern than in patients with HFP pattern. CONCLUSIONS: In patients with STEMI and LV dysfunction doxycycline can favorably modulate the LV filling pattern early after primary PCI.

A New Risk Score to Predict Long-Term Cardiac Mortality in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock and Treated With Primary Percutaneous Intervention.

Poor data exist about predictors of long-term cardiac mortality in patients presenting acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) treated with primary percutaneous coronary intervention (p-PCI), and current risk-adjustment models in this setting are not adequate. We retrospectively analyzed our registry of patients with AMI treated with p-PCI. The aim of this study was to identify the independent predictors of 2-year cardiac mortality in patients presenting CS. A Risk Score was created assigning at any independent variable a value directly correlated with its power to increase mortality. From 1995 to 2013, 4,078 consecutive patients underwent primary PCI for AMI. Of these, 388 patients (10.5%) had CS on admission. The p-PCI procedural success was 85%. At 2-year follow-up, the overall cardiac mortality rate was 48%. The independent predictors related with mortality were: out of hospital cardiac arrest (OHCA) (hazard ratio [HR] 1.51; p = 0.04), age >75 years (HR 2.09; p ≤0.001), and failure p-PCI (HR 2.30; p <0.001). On the basis of the HR obtained, we assigned an incremental value to each independent variable identified (OHCA: 0.5 points, age>75 years: 1 point, failed p-PCI: 1.5 points). The mortality rates among different score risk level were highly significant (p <0.001): 32% score risk 1 (points 0), 58% score risk 2 (points 0.5-2), and 83% score risk 3 (points >2), respectively. In conclusion, OHCA, age >75 years, and failed p-PCI are strong predictors of 2-year cardiac mortality. On the basis of this, a rapid score tool could be useful to identify patients at major risk of death.

Angiographic and Clinical Outcomes After Everolimus-Eluting Stenting for Unprotected Left Main Disease and High Anatomic Coronary Complexity.

OBJECTIVES: This study determined angiographic and clinical outcomes after everolimus-eluting stent (EES)-supported percutaneous coronary intervention for unprotected left main disease (ULMD) and high SYNTAX (SYNergy between PCI with TAXus and Cardiac Surgery) trial score (≥33). BACKGROUND: The SYNTAX trial has shown the superiority of coronary surgery over percutaneous coronary intervention (PCI) in patients with ULMD and complex coronary anatomy. It has been hypothesized that, if newer generation drug-eluting stents had been used in the SYNTAX trial, there would have been a significant reduction in clinical events. METHODS: Patients had angiograms scored according to the SYNTAX score algorithm and were divided into 2 groups: those with SYNTAX score of ≥33 and those with <33. The main endpoints were ULMD restenosis and 3-year cardiac mortality. RESULTS: From May 2008 to July 2014, 393 patients underwent EES implantation for ULMD (181 patients had a SYNTAX score ≥33, whereas 212 patients had a SYNTAX score <33). Overall, the restenosis rate was 4.9% (6% in SYNTAX patients scoring ≥33 and 4.1% in SYNTAX patients scoring <33; p = 0.399). On multivariate analysis, the only variable related to restenosis was stent length (odds ratio [OR]: 1.06; 95% confidence interval [CI]: 1.02 to 1.09; p = 0.002). Three-year cardiac survival rates were 99 ± 1% and 98 ± 2% in patients with European system for cardiac operative risk evaluation (EuroSCORE) <6 and SYNTAX <33 and ≥33, respectively, and 90 ± 3% and 87 ± 3% in patients with a EuroSCORE >6 and SYNTAX score <33 and ≥33, respectively. EuroSCORE was strongly related to cardiac mortality, while the SYNTAX score ≥33 was not both in patients with a EuroSCORE <6 or ≥6, and there were no interactions between EuroSCORE and SYNTAX score ≥33. CONCLUSIONS: For ULMD patients, high anatomical complexity as defined by a SYNTAX score ≥33 is not predictive of clinical outcome after PCI. (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972).

Prognostic impact of high residual platelet reactivity after chronic total occlusion percutaneous coronary intervention in patients with diabetes mellitus.

BACKGROUND: The study sought to determine the impact of high residual platelet reactivity (HRPR) on long-term cardiac mortality in diabetic patients treated with PCI for CTO. No data exist about the impact of HRPR after 600 mg clopidogrel loading on long-term clinical outcome in patients with diabetes mellitus and treated with percutaneous coronary angioplasty (PCI) for chronic total occlusion (CTO). METHODS: From the Florence CTO-PCI registry, we identified consecutive diabetic patients with available in vitro platelet reactivity assessment by light transmittance aggregometry after a loading dose of 600 mg of clopidogrel. HRPR was defined as residual platelet aggregation by 10 µmol/L ADP test ≥70%. The primary end point of the study was long-term cardiac mortality. RESULTS: Two-hundred and three diabetic patients underwent CTO-PCI. The incidence of HRPR was 23%. The 3-year cardiac survival was lower in the HRPR group than the low residual platelet reactivity (LRPR) group (70 ± 7% and 92 ± 3%, respectively; p=0.001). Within the oral antidiabetic patients there were no significant differences in long-term survival between HRPR and LRPR groups. Conversely, the association of insulin therapy and HRPR was related to a dramatic decrease in survival compared to the LRPR group (34 ± 14% vs. 89 ± 4%; p<0.001). At multivariable analysis insulin therapy (HR 4.31; p=0.001) and HRPR (HR 3.26; p=0.004) were significantly related to long-term mortality, while completeness of revascularization was inversely related to cardiac mortality (HR 0.40; p=0.029). CONCLUSION: HRPR is a strong marker of increased risk of cardiac death in patients with DM who underwent PCI for CTO.

Matrix metalloproteinases and their tissue inhibitor after reperfused ST-elevation myocardial infarction treated with doxycycline. Insights from the TIPTOP trial.

BACKGROUND: The TIPTOP (Early Short-term Doxycycline Therapy In Patients with Acute Myocardial Infarction and Left Ventricular Dysfunction to Prevent The Ominous Progression to Adverse Remodelling) trial demonstrated that a timely, short-term therapy with doxycycline is able to reduce LV dilation, and both infarct size and severity in patients treated with primary percutaneous intervention (pPCI) for a first ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction. In this secondary, pre-defined analysis of the TIPTOP trial we evaluated the relationship between doxycycline and plasma levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). METHODS: In 106 of the 110 (96%) patients enrolled in the TIPTOP trial, plasma MMPs and TIMPs were measured at baseline, and at post-STEMI days 1, 7, 30 and 180. To evaluate the remodeling process, 2D-Echo studies were performed at baseline and at 6months. A (99m)Tc-SPECT was performed to evaluate the 6-month infarct size and severity. RESULTS: Doxycycline therapy was independently related to higher plasma TIMP-2 levels at day 7 (p<0.05). Plasma TIMP-2 levels above the median value at day 7 were correlated with the 6-month smaller infarct size (3% [0%-16%] vs. 12% [0%-30%], p=0.002) and severity (0.55 [0.44-0.64] vs. 0.45 [0.29-0.60], p=0.002), and LV dilation (-1ml/m(2) [from -7ml/m(2) to 9ml/m(2)] vs. 3ml/m(2) [from -2ml/m(2) to 19ml/m(2)], p=0.04), compared to their counterpart. CONCLUSIONS: In this clinical setting, doxycycline therapy results in higher plasma levels of TIMP-2 which, in turn, inversely correlate with 6month infarct size and severity as well as LV dilation.

Impact of chronic total occlusion revascularization in patients with acute myocardial infarction treated by primary percutaneous coronary intervention.

Coronary chronic total occlusion (CTO) carries a poor outcome in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI). We sought to investigate the prognostic impact of a staged successful CTO-PCI in patients with AMI treated with primary PCI. Outcome analysis included consecutive patients treated by successful primary PCI with coexisting non-infarct-related artery CTO who survived after 1 week from AMI. A comparison between patients with successful CTO-PCI and patients with failed or nonattempted CTO-PCI was performed. The primary end points of the study were 1-year and 3-year cardiac survival. Of 1,911 patients who underwent successful primary PCI for AMI from 2003 to 2012, 169 (10%) had non-infarct-related artery CTO of a major branch. A staged CTO-PCI attempt was performed in 74 patients (44%) and was successful in 58 (success rate 78%). All patients with successful CTO-PCI received drug-eluting stents. In the successful CTO-PCI group, a complete coronary revascularization was achieved in 88% of the patients. The 1-year cardiac mortality rate was 1.7% in the successful CTO-PCI group and 12% in nonattempted or failed CTO-PCI group (p = 0.025). Successful CTO-PCI was an independent predictor of 3-year cardiac survival (hazard ratio 0.20, 95% confidence interval 0.05 to 0.92, p = 0.038). In conclusion, successful CTO-PCI in survivors after primary PCI is associated with improved long-term cardiac survival.

Effects of a timely therapy with doxycycline on the left ventricular remodeling according to the pre-procedural TIMI flow grade in patients with ST-elevation acute myocardial infarction.

Doxycycline has been demonstrated to reduced left ventricular (LV) remodeling, but its effect in patients with ST-elevation myocardial infarction (STEMI) and a baseline occluded [thrombolysis in myocardial infarction (TIMI) flow grade ≤1] infarct-related artery (IRA) is unknown. According to the baseline TIMI flow grade, 110 patients with a first STEMI were divided into 2 groups. Group 1: 77 patients with TIMI flow ≤1 (40 patients treated with doxycycline and 37 with standard therapy, respectively), and a Group 2: 33 patients with TIMI flow 2-3 (15 patients treated with doxycycline and 18 with standard therapy, respectively). The two randomized groups were well matched in baseline characteristics. A 2D-Echo was performed at baseline and at 6 months, together with a coronary angiography, for the remodeling and IRA patency assessment, respectively. The LV end-diastolic volume index (LVEDVi) decreased in Group 2 [-3 mL/m(2) (IQR: -12 to 4 mL/m(2))], and increased in Group 1 [6 mL/m(2) (IQR: -2 to 14 mL/m(2))], (p = 0.001). In Group 2, LVEDVi reduction was similar regardless of drug therapy, while in Group 1 the LVEDVi was smaller in patients treated with doxycycline as compared to control [3 mL/m(2) (IQR: -3 to 8 mL/m(2)) vs. 10 mL/m(2) (IQR: 1-27 mL/m(2)), p = 0.006]. A similar pattern was observed also for LV end-systolic volume and ejection fraction. In STEMI patients at higher risk, as those with a baseline TIMI flow grade ≤1, doxycycline reduces LV remodeling.

Early short-term doxycycline therapy in patients with acute myocardial infarction and left ventricular dysfunction to prevent the ominous progression to adverse remodelling: the TIPTOP trial.

AIMS: Experimental studies suggest that doxycycline attenuates post-infarction remodelling and exerts protective effects on myocardial ischaemia/reperfusion injury. However, the effects of the drug in the clinical setting are unknown. The aim of this study was to examine the effect of doxycycline on left ventricular (LV) remodelling in patients with acute ST-segment elevation myocardial infarction (STEMI) and LV dysfunction. METHODS AND RESULTS: Open-label, randomized, phase II trial. Immediately after primary percutaneous coronary intervention, patients with STEMI and LV ejection fraction < 40% were randomly assigned to doxycycline (100 mg b.i.d. for 7 days) in addition to standard therapy, or to standard care. The echo LV end-diastolic volumes index (LVEDVi) was determined at baseline and 6 months. (99m)Tc-Sestamibi-single-photon emission computed tomography infarct size and severity were assessed at 6 months. We calculated a sample size of 110 patients, assuming that doxycycline may reduce the increase in the LVEDVi from baseline to 6 months > 50% compared with the standard therapy (statistical power > 80% with a type I error = 0.05). The 6-month changes in %LVEDVi were significant smaller in the doxycycline group than in the control group [0.4% (IQR: -16.0 to 14.2%) vs.13.4% (IQR: -7.9 to 29.3%); P = 0.012], as well as infarct size [5.5% (IQR: 0 to 18.8%) vs. 10.4% (IQR: 0.3 to 29.9%) P = 0.052], and infarct severity [0.53 (IQR: 0.43-0.62) vs. 0.44 (IQR: 0.29-0.60), P = 0.014], respectively. CONCLUSION: In patients with acute STEMI and LV dysfunction, doxycycline reduces the adverse LV remodelling for comparable definite myocardial infarct size (NCT00469261).

Predictors of reocclusion after successful drug-eluting stent-supported percutaneous coronary intervention of chronic total occlusion.

OBJECTIVES: This study sought to assess the incidence of reocclusion and identification of predictors of angiographic failure after successful chronic total occlusion (CTO) drug-eluting stent-supported percutaneous coronary intervention (PCI). BACKGROUND: Large registries have shown a survival benefit in patients with successful CTO PCI. Intuitively, sustained vessel patency may be considered as a main variable related to long-term survival. Very few data exist about the angiographic outcome after successful CTO PCI. METHODS: The Florence CTO PCI registry started in 2003 and included consecutive patients treated with drug-eluting stents for at least 1 CTO (>3 months). The protocol treatment included routine 6- to 9-month angiographic follow-up. Clinical, angiographic, and procedural variables were included in the model of multivariable binary logistic regression analysis for the identification of the predictors of reocclusion. RESULTS: From 2003 to 2010, 1,035 patients underwent PCI for at least 1 CTO. Of these, 802 (77%) had a successful PCI. The angiographic follow-up rate was 82%. Reocclusion rate was 7.5%, whereas binary restenosis (>50%) or reocclusion rate was 20%. Everolimus-eluting stents were associated with a significantly lower reocclusion rate than were other drug-eluting stents (3.0% vs. 10.1%; p = 0.001). A successful subintimal tracking and re-entry technique was associated with a 57% of reocclusion rate. By multivariable analysis, the subintimal tracking and re-entry technique (odds ratio [OR]: 29.5; p < 0.001) and everolimus-eluting stents (OR: 0.22; p = 0.001) were independently related to the risk of reocclusion. CONCLUSIONS: Successful CTO-PCI supported by everolimus-eluting stents is associated with a very high patency rate. Successful subintimal tracking and re-entry technique is associated with a very low patency rate regardless of the type of stent used.

The impact of right coronary artery chronic total occlusion on clinical outcome of patients undergoing percutaneous coronary intervention for unprotected left main disease.

OBJECTIVES: The aim of the present study was to investigate whether right coronary artery chronic total occlusion (CTO) carries prognostic implications in patients undergoing drug-eluting stent-supported percutaneous coronary intervention (PCI) for unprotected left main disease (ULMD). BACKGROUND: No data exist on the prognostic implication of CTO in patients undergoing PCI for ULMD. METHODS: Prospective registry of consecutive patients undergoing PCI for ULMD. Patients with ST-segment elevation myocardial infarction were excluded. Primary endpoints were 6-month and long-term cardiac mortality. RESULTS: From January 2004 to December 2009, 330 patients underwent PCI for ULMD. Of the 330 patients, 78 (24%) had CTO of the right coronary artery, 22 (7%) had CTO of the left anterior descending artery, and 16 (5%) had CTO of the left circumflex artery. Patients with right coronary artery CTO had a higher risk profile compared with patients without right coronary artery CTO. The 6-month mortality rate was 12.8% in patients with right coronary artery CTO, and 3.6% in patients without right coronary artery CTO (p < 0.002), and the 3-year cardiac survival rate was 76.4 ± 6.8% and 89.7 ± 2.7% (p < 0.003), respectively. By multivariable analysis, the only 2 independent predictors of 3-year cardiac mortality were right coronary artery CTO (hazard ratio: 2.15, 95% confidence interval: 1.02 to 4.50; p = 0.043) and EuroSCORE (hazard ratio: 1.03, 95% confidence interval: 1.02 to 1.05; p < 0.001). CONCLUSIONS: Right coronary artery CTO occurs frequently and is a significant predictor of mortality in patients with ULMD undergoing PCI.

Comparison of everolimus-eluting stent with paclitaxel-eluting stent in long chronic total occlusions.

The aim of the present study was the comparison of the everolimus-eluting stent (EES) with the paclitaxel-eluting stent (PES) in patients treated for long chronic total occlusions (CTOs). Previous randomized trials have shown the superiority of EESs over PESs. No data exist about the efficacy and safety of EESs in patients treated for complex CTOs requiring multiple stent implantation. We identified 258 patients treated for CTOs who received multiple EESs (n = 112) or PESs (n = 146), with a total stent length of ≥40 mm. The primary end point was in-segment restenosis, defined as >50% luminal narrowing at the segment site, including the stent and 5 mm proximal and distal to the stent edges of the target vessel, on the follow-up angiogram. The secondary end point was the 9-month composite of major adverse cardiovascular events. The 2 patient groups were similar in all baseline characteristics. The median lesion length was 48 mm in the EES group and 46 mm in the PES group (p = 0.793). The incidence of the primary end point of the study was 11.8% in the EES group and 31.4% in the PES group (p = 0.001). The major adverse cardiovascular event rate was lower in the EES group than in the PES group (8.9% and 22.6%, respectively, p = 0.003). Definite or probable stent thrombosis occurred in 5 patients in the PES group (3.4%), with no stent thrombosis occurring in the EES group (p = 0.048). On multivariate analysis, EES was the only variable independently related to the risk of binary angiographic restenosis with an odds ratio of 0.29 (95% confidence interval 0.14 to 0.62; p = 0.002). In conclusion, in patients treated for long CTOs and requiring multiple stent implantation, EESs performed better than PESs, with a >50% reduction in the risk of restenosis and major adverse cardiovascular events.

Relationship between infarct size and severity measured by gated SPECT and long-term left ventricular remodelling after acute myocardial infarction.

PURPOSE: After acute myocardial infarction (AMI), left ventricular (LV) remodelling may occur despite successful reperfusion. This study aimed to investigate by gated single photon emission computed tomography (SPECT) the long-term evolution of myocardial perfusion and LV function after AMI and to identify the predictors of LV remodelling. METHODS: Sixty-eight AMI patients successfully treated by primary percutaneous coronary intervention underwent (99m)Tc-sestamibi gated SPECT at 1 month (baseline) and over 6-month follow-up after the acute event. LV remodelling was defined as 20% increase in LV end-diastolic volume at follow-up. RESULTS: At baseline, patients with remodelling (n = 14) showed larger (infarct size 29.3 ± 7.8%) and more transmural (infarct severity 0.28 ± 0.10) infarctions, and reduced LV ejection fraction (35.4 ± 5.6%), but similar LV volume indexes, compared to patients without remodelling (n = 54) (infarct size 20.8 ± 14.4%, p < 0.05, infarct severity 0.40 ± 0.11, p < 0.001, ejection fraction 44.5 ± 9.2, p < 0.001). At stepwise multivariate regression analysis, infarct severity showed the best predictive value for predicting LV remodelling (F = 5.54, p < 0.05). Using the thresholds identified by receiver-operating characteristic curve analysis, infarct size and severity detected patients with remodelling with 75% accuracy and 95% negative predictive value. Infarct resorption (defined as the defect size difference between follow-up and baseline) was comparable between patients with (-4.4 ± 8.4%) and without remodelling (-6.8 ± 9.4%) (p = NS). CONCLUSION: Perfusion parameters assessed by gated SPECT in the subacute phase after successfully treated AMI correlate with changes in functional parameters at long-term follow-up. Infarct severity is more effective than infarct size, but both are helpful for predicting LV remodelling.

Predictor of stent thrombosis in patients treated with turbostratic carbon-coated stent implantation for acute myocardial infarction.

BACKGROUND: Stent thrombosis is a major complication after percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction (AMI) and is associated with reinfarction and increased risk of death. METHODS: Patients treated with the turbostratic carbon-coated stent (CID, Saluggia, Italy) for AMI were identified from a prospective primary PCI database. Primary end-point was stent thrombosis within 6 months. Forward stepwise Cox proportional hazards analysis was used to identify independent predictors of stent thrombosis. RESULTS: Between 2001 and 2008, 746 patients underwent turbostratic carbon-coated stent implantation for AMI. Patients had a mean age of 65 ± 12 years, 9% had cardiogenic shock on admission, 48% had multivessel coronary disease, 78% had baseline target vessel TIMI grade 0-1. Multiple stent implantation was performed in 26% of patients. The majority of patients (78%) received abciximab treatment and a postprocedural TIMI grade 3 flow was achieved in 98% patients. Definite stent thrombosis occurred in 10 patients (1.3%), while three patients (0.4%) had possible stent thrombosis. No probable stent thrombosis occurred. There were no procedural stent thromboses. In patients who received abciximab stent thrombosis the rate was 1%, while it was 4.3% in patients not receiving abciximab treatment. After adjusting for all clinical, angiographic, and procedural variables, abciximab treatment (HR 0.17; 95% CI 0.05-0.56, P = 0.003) and major bleedings (HR 14.2; 85% CI 2.79-72.44, P = 0.001) were the only two predictors related to stent thrombosis. CONCLUSIONS: Patients with AMI treated with turbostratic carbon-coated stent implantation and abciximab treatment have a low incidence of stent thrombosis. Abciximab treatment along with major bleeding complications are the only predictors related to stent thrombosis.

Comparison of bivalirudin and unfractionated heparin plus protamine in patients with coronary heart disease undergoing percutaneous coronary intervention (from the Antithrombotic Regimens aNd Outcome [ARNO] trial).

Previous studies have compared bivalirudin and unfractionated heparin (UFH) plus the routine use of glycoprotein IIb/IIIa inhibitors. They have demonstrated that bivalirudin can decrease bleeding complications without a significant increase in ischemic complications, resulting in a better net clinical outcome, as defined by the efficacy (ischemic complications) or safety (bleeding complications) end point. The aim of the present study was to compare bivalirudin and UFH plus protamine in patients undergoing elective percutaneous coronary intervention and pretreated with clopidogrel and aspirin. We randomly assigned 850 patients with stable or unstable coronary artery disease to bivalirudin or UFH followed by protamine at the end of the percutaneous coronary intervention. The primary end point was in-hospital major bleeding. The main secondary end points were the 1-month composite of death, myocardial infarction, unplanned target vessel revascularization; and the 1-month net clinical outcome. The rate of major bleeding (primary end point) was 0.5% in patients randomized to bivalirudin and 2.1% in patients randomized to UFH (p = 0.033). At 30 days, the rate of major bleeding was 0.9% in the bivalirudin arm and 2.8% in the UFH arm (p = 0.043). The composite of death, myocardial infarction, and target vessel revascularization rate and the net clinical outcome rate was 2.8% and 6.4% (p = 0.014) and 3.3% and 7.8% (p = 0.004), respectively, in the bivalirudin and UFH arms. In conclusion, in percutaneous coronary intervention patients pretreated with clopidogrel and aspirin, bivalirudin was associated with less major bleeding and fewer ischemic complications and a better net clinical outcome than UFH.

High residual platelet reactivity after clopidogrel loading and long-term clinical outcome after drug-eluting stenting for unprotected left main coronary disease.

BACKGROUND: No data exist about the impact of high residual platelet reactivity (HRPR) after clopidogrel loading on long-term clinical outcome in patients undergoing drug-eluting stent (DES) implantation for unprotected left main disease (ULMD). METHODS AND RESULTS: Consecutive patients who underwent percutaneous coronary intervention for ULMD had prospective platelet reactivity assessment by light transmittance aggregometry after a loading dose of 600 mg of clopidogrel. The primary end point of the study was cardiac mortality, and the secondary end point was stent thrombosis. From January 2005 to September 2008, 215 consecutive patients were treated with DES for ULMD. The incidence of HRPR after clopidogrel loading was 18.6%. The median follow-up was 19.3 months. The overall estimated 1-, 2- and 3-year cardiac mortality rate was 3.9+/-1.3%, 7.5+/-2.2%, and 12.2+/-3.4%, respectively. The 3-year cardiac mortality rate was 8.0+/-3.1% in the low residual platelet reactivity (LRPR) group and 28.3+/-10.4% in the HRPR group (P=0.005). The 3-year stent thrombosis rate was 4.2+/-1.8% in the low residual platelet reactivity group and 16.0+/-7.3% in the HRPR group (P=0.021). By forward stepwise regression analysis, HRPR after clopidogrel loading was the only independent predictor of cardiac death (hazard ratio, 3.82; 95% confidence interval,1.38 to 10.54; P=0.010) and stent thrombosis (hazard ratio, 3.69; 95% confidence interval, 1.12 to 12.09; P=0.031). CONCLUSIONS: HRPR after 600-mg clopidogrel loading is a strong marker of increased risk of cardiac death and DES thrombosis in patients receiving DES stenting for ULMD. Routine assessment of in vitro residual platelet reactivity after clopidogrel loading in patients with ULMD potentially suitable for DES-supported percutaneous coronary intervention should be considered to guide patient care decisions.

Relationship of sustained brain natriuretic peptide release after reperfused acute myocardial infarction with gated SPECT infarct measurements and its connection with collagen turnover and left ventricular remodeling.

BACKGROUND: The relationship among plasma brain natriuretic peptide (BNP), markers of extracellular matrix (ECM) remodeling, and left ventricular (LV) dilation after reperfused acute myocardial infarction is poorly known. METHODS AND RESULTS: Echocardiogram, plasma BNP, and ECM degradation markers (serum amino-terminal telopeptide of type I procollagen and type III procollagen and carboxy-terminal telopeptide of type I procollagen [ICTP]) were evaluated in 34 patients at days 1, 3, and 30 after first reperfused acute myocardial infarction. At 1 month, infarct size and severity and LV volume were measured by sestamibi gated single photon emission computed tomography. Patients were stratified according to day 3 BNP levels into 2 groups: group 1 (n = 17) had BNP values over the median value, and group 2 (n = 17) had BNP values under the median value. Infarct size and severity were similar in the 2 groups. LV volumes increased in group 1 but decreased in group 2 (P < .01). BNP values, LV volume/mass index, and infarct size were independent predictors of 1-month LV dilation (beta = .58 [P = .001], beta = .41 [P = .01], and beta = .32 [P = .03], respectively). Levels of serum amino-terminal propeptide of type I procollagen and type III procollagen were similar in both groups. The level of ICTP increased significantly in group 1 only, and after 3 days, it was higher (P < .01) than in group 2. In group 1 ICTP significantly interacted with the relationship between BNP release and serial changes in LV volumes (F = 4.87, P = .03). CONCLUSIONS: ICTP is related to elevated BNP level independently of infarct size and severity and interacts with the relationship between BNP and LV dilation. BNP levels could play a role in LV remodeling by favoring ECM degradation.

Impact of complete revascularization with percutaneous coronary intervention on survival in patients with at least one chronic total occlusion.

AIMS: This study sought to determine the impact on survival of successful drug-eluting stent-supported percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). METHODS AND RESULTS: Comparison of long-term cardiac survival of consecutive patients who underwent PCI for at least one CTO and who were stratified into successful and failure procedures. From 2003 to 2006, 486 patients underwent PCI for 527 CTO. CTO-PCI was successful in 344 patients (71%) and 361 lesions (68%). Multivessel PCI was performed in 62% in the CTO-PCI failure group and in 71% in the CTO-PCI success group (P = 0.062). Cardiac survival rate was higher in the CTO-PCI success group compared with CTO-PCI failure group (91.6 +/- 2.0 vs. 87.4 +/- 2.9%; P = 0.025), in patients with multivessel disease and CTO-PCI success compared with CTO-PCI failure (91.4 +/- 2.2 vs. 86.6 +/- 3.1%; P = 0.021), and in patients with complete revascularization when compared to patients with incomplete revascularization (94.0 +/- 1.7 vs. 83.8 +/- 3.6%; P < 0.001). CONCLUSION: Successful CTO-PCI confers a long-term survival benefit. Improvement in survival is driven by the differences in the outcome of patients with multivessel disease and who were completely revascularized.