Bifurcation PCI with a hybrid strategy with drug- eluting balloons versus a stepwise provisional two- stent strategy: Rationale and design of the hybrid DEB study.

The optimal treatment strategy for coronary bifurcation lesions by percutaneous coronary intervention (PCI) is complex and remains a subject of debate. Current guidelines advise a stepwise provisional approach with optional two-stent strategy. However, a two-stent strategy, both upfront and stepwise provisional, is technically demanding. Therefore, there is increasing interest in the use of drug-eluting balloons (DEB) in bifurcation lesions, mainly after a provisional approach with unsatisfactory result of the side branch. Some small pilot studies already showed that the use of DEB in bifurcation lesions is safe and feasible. However, a randomized comparison of this hybrid DEB strategy with a two-stent strategy is currently lacking. TRIAL DESIGN: The Hybrid DEB study is a prospective, multicenter, randomized controlled trial investigating noninferiority of a hybrid DEB approach, using a combination of a drug-eluting stent (DES) in the main vessel and DEB in the side branch, compared to stepwise provisional two-stent strategy in patients with true bifurcation lesions. A total of 500 patients with de novo true coronary bifurcation lesions, treated with a stepwise provisional approach and an unsatisfactory result of the side branch after main vessel stenting (≥ 70% stenosis and/or < thrombolysis in myocardial infarction III flow), will be randomized in a 1:1 ratio to receive either treatment with a DEB or with a DES in the side branch. The primary endpoint is a composite endpoint of the occurrence of all-cause death, periprocedural or spontaneous myocardial infarction and/or target vessel revascularization at the anticipated median 2-year follow-up. CONCLUSION: The Hybrid DEB study will compare in a multicenter, randomized fashion a hybrid DEB approach with a stepwise provisional two-stent strategy in patients with true bifurcation lesions. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT05731687.

Pooled Analysis Comparing the Efficacy of Intracoronary Versus Intravenous Abciximab in Smokers Versus Nonsmokers Undergoing Primary Percutaneous Coronary Revascularization for Acute ST-Elevation Myocardial Infarction.

Cigarette smokers with ST-segment elevation myocardial infarction (STEMI) may present different response to potent antithrombotic therapy compared to nonsmokers. We assessed the impact of smoking status and intracoronary abciximab in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). We pooled data from 5 randomized trials comparing intracoronary versus intravenous abciximab bolus in patients undergoing primary PCI. The primary end point was the composite of death or reinfarction at a mean follow-up of 292 ± 138 days. Of 3,158 participants, 1,369 (43.3%) were smokers, and they had a lower risk of the primary end point in crude, but not in adjusted analyses (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.63 to 1.21, p = 0.405). Intracoronary versus intravenous abciximab was associated with a significant reduction in the risk of primary end point among smokers (3.6% vs 8.0%; HR 0.43, 95% CI 0.26 to 0.72, p = 0.001), but not in nonsmokers (10.2% vs 9.9%; HR 0.99, 95% CI 0.72 to 1.36, p = 0.96), with a significant interaction (p = 0.009). Furthermore, intracoronary abciximab decreased the risk of reinfarction in smokers (HR 0.30, 95% CI 0.15 to 0.62, p = 0.001), with no difference in nonsmokers (HR 1.20, 95% CI 0.71 to 2.01, p = 0.50). Stent thrombosis was lowered by intracoronary abciximab in smokers (HR 0.28, 95% CI 0.06 to 0.66, p = 0.009), but was ineffective in nonsmokers (HR 1.04, 95% CI 0.54 to 2.00, p = 0.903). Interaction testing showed heterogeneity in treatment effect for reinfarction (p = 0.002) and stent thrombosis (p = 0.018) according to smoking status. In conclusion, among patients with STEMI undergoing primary PCI, smoking status did not affect the adjusted risk of clinical events. Intracoronary abciximab bolus improved clinical outcomes by reducing the risk of death or reinfarction.

Intracoronary abciximab in diabetic patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Although intracoronary abciximab failed to improve prognosis compared with intravenous route in unselected ST-segment elevation myocardial infarction (STEMI) patients, little is known about the role of intracoronary abciximab in diabetic patients. OBJECTIVES: To evaluate the efficacy of intracoronary abciximab administration in diabetic patients with STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS: Reperfusional and clinical outcomes of intracoronary abciximab compared with intravenous bolus abciximab according to diabetic status were evaluated in a pooled analysis of five randomized trials including 3158 STEMI patients. The primary clinical endpoint of the study was the composite of death or reinfarction at 30-day follow-up. RESULTS: Among 584 diabetic patients (18.5%), the composite of death or reinfarction was significantly reduced with intracoronary abciximab compared to intravenous abciximab (4.7% vs. 8.8%; rate ratio [RR], 0.50; 95% confidence intervals [CI], 0.26-0.99; p=0.04), driven by numerically lower deaths (3.7% vs. 6.4%; RR, 0.56; 95% CI, 0.26-1.20; p=0.13). Moreover, a significant reduction in definite or probable stent thrombosis was observed in patients receiving intracoronary abciximab (1% vs. 3.5%; RR, 0.27; 95% CI, 0.07-0.99; p=0.04). Although formal tests for interaction were not significant, no clinical benefit was apparent in the cohort of STEMI patients without diabetes (n=2574). CONCLUSIONS: In diabetic patients with STEMI undergoing primary PCI, intracoronary abciximab may improve clinical outcomes as compared with standard intravenous use. These findings require confirmation in a dedicated randomized trial.

Soluble interleukin 6 receptor levels are associated with reduced myocardial reperfusion after percutaneous coronary intervention for acute myocardial infarction.

AIMS: Interleukin-6 receptor (IL-6R) signalling has been suggested to play a causal role in the development and outcome of coronary heart disease (CHD). The aim of this study was to investigate the association of sIL-6R levels with myocardial reperfusion after percutaneous coronary intervention (PCI) for acute ST-elevated myocardial infarction (STEMI). METHODS: Blood was sampled from 70 patients presenting with STEMI at 6 different time-points (baseline, post-PCI, t=1h, t=6h, t=24h, t=2w). Coronary angiograms post-PCI were analysed for myocardial blush grade (MBG) as indicator of myocardial reperfusion. Serum IL-6 and sIL-6R were measured using IL-6 and sIL-6R enzyme-linked immunosorbent assays (ELISA). RESULTS: sIL-6R levels fluctuated biphasic during the two weeks after STEMI. Reduced MBG was associated with a larger change in sIL-6R levels between baseline and post-PCI compared to optimal MBG (-13.40; SEM 2.78ng/ml vs -1.99; SEM 2.35ng/ml, respectively; p<0.001). Patients with reduced MBG also showed a larger increase in sIL-6R levels after PCI and 1h after myocardial infarction (MI) compared to optimal MBG (respectively 11.56; SEM 2.68ng/ml vs 3.02; SEM 2.39ng/ml; p=0.018). IL-6/sIL-6R ratio was also more increased in patients with reduced MBG at 24h after myocardial infarction (0.23; SEM 0.08-0.51 vs 0.10; SEM 0.05-0.21; p=0.024). An optimal MBG was associated with a 10ng increase in sIL-6R level between baseline and post-PCI (OR 1.687, CI 1.095-2.598; p=0.018). CONCLUSIONS: sIL-6R levels fluctuate biphasic during the two weeks after MI with larger changes and increased IL-6/sIL-6R ratio in patients with reduced MBG. Further research is needed to increase our understanding of the possible causality of these associations.

Uninterrupted oral anticoagulation versus bridging in patients with long-term oral anticoagulation during percutaneous coronary intervention: subgroup analysis from the WOEST trial.

AIMS: To investigate the optimal periprocedural antithrombotic strategy in patients on long-term oral anticoagulation (OAC) who require percutaneous coronary intervention with stenting. METHODS AND RESULTS: The WOEST study was a randomised controlled trial which recruited 573 patients on long-term OAC who underwent PCI. The periprocedural treatment strategy was left to the operator's discretion. To assess the safety and feasibility of uninterrupted oral anticoagulation (UAC) and bridging therapy (BT), bleeding complications and MACCE were assessed in patients treated according to UAC (n=241) and BT (n=322) regimen. After 30 days, as well as after one year, there were no significant differences in bleeding complications (HR 1.14, 95% CI: 0.77-1.69, p=0.51, and HR 1.26, 95% CI: 0.94-1.69, p=0.12, respectively) and MACCE. MACCE tended to be less frequent in the UAC group (respectively HR 0.48, 95% CI: 0.15-1.51, p=0.21, and HR 0.72, 95% CI: 0.46-1.14, p=0.16). Additionally, adjustment with a propensity score revealed no significant differences. Periprocedural INR was not associated with bleeding or MACCE. CONCLUSIONS: In the WOEST study, UAC was not associated with an increase of bleeding or MACCE compared to bridging therapy. This is the largest study up to now to support the current guidelines. The WOEST trial is registered with ClinicalTrials.gov, number NCT00769938.

Effects of baseline coronary occlusion and diabetes mellitus in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Several studies have highlighted the prognostic role of preprocedural Thrombolysis In Myocardial Infarction (TIMI) flow in the infarct-related artery (IRA) in patients with ST-segment elevation myocardial infarction (STEMI). However, the impact of preprocedural IRA occlusion in patients with diabetes with STEMI has been insufficiently studied. The aim of this study was to evaluate the effects of baseline IRA occlusion and diabetic status in patients with STEMI who underwent primary percutaneous coronary intervention by using data from a pooled analysis of randomized trials comparing intracoronary with intravenous abciximab bolus administration. A total of 3,046 patients with STEMI who underwent primary percutaneous coronary intervention were included. Diabetes was present in 578 patients (19%). The primary outcome was mortality after a median follow-up period of 375 days. Secondary end points were reinfarction and stent thrombosis. In patients without diabetes, IRA occlusion versus no occlusion was not associated with increased rates of mortality (4.3% vs 2.7%, p = 0.051) and reinfarction (3.3% vs 2.5%, p = 0.33). Patients with diabetes with IRA occlusion compared with those without occlusion showed higher rates of mortality (10.6% vs 4.6%, p = 0.01) and reinfarction (5.6% vs 2.1%, p = 0.03). Baseline IRA occlusion increased the rate of stent thrombosis in the nondiabetic (2.1% vs 1.0%, p = 0.04) and diabetic (3.2% vs 0.8%, p = 0.05) cohorts. Interaction analysis demonstrated that the risk for death and reinfarction was significantly increased when diabetes and IRA occlusion occurred concomitantly. In conclusion, patients with STEMI with diabetes and baseline IRA occlusion had disproportionately higher rates of death and reinfarction. Preprocedural IRA occlusion increased the risk for stent thrombosis, irrespective of diabetic status.

Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial.

IMPORTANCE: Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function. OBJECTIVE: To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI). DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013. INTERVENTIONS: Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months. MAIN OUTCOMES AND MEASURES: The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure. RESULTS: At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed. CONCLUSIONS AND RELEVANCE: Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01217307.

Intracoronary versus intravenous bolus abciximab administration in patients undergoing primary percutaneous coronary intervention with acute ST-elevation myocardial infarction: a pooled analysis of individual patient data from five randomised controlled trials.

AIMS: In recent years, intracoronary bolus abciximab has emerged as an alternative to the standard intravenous route in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The aim of the current study was to perform an individual patient-level pooled analysis of randomised trials, comparing intracoronary versus intravenous abciximab bolus use in STEMI patients undergoing primary PCI. METHODS AND RESULTS: Individual data of 3,158 patients enrolled in five trials were analysed. Reperfusion endpoints were: post-procedural Thrombolysis in Myocardial Infarction (TIMI) 3 flow, myocardial blush grade (MBG) 2/3 and complete ST-segment resolution. The primary clinical endpoint of interest was the composite of death and reinfarction at 30 days. Compared with the intravenous route, intracoronary abciximab bolus administration did not improve TIMI 3 flow (odds ratio [OR] 1.19; 95% confidence interval [CI]: 0.90-1.59; p=0.23) and complete ST-segment resolution (OR 1.22, 95% CI: 0.92-1.63, p=0.17), but increased MBG 2/3 occurrence (OR 1.83, 95% CI: 1.05-3.18, p=0.03). At 30-day follow-up, intracoronary bolus abciximab did not reduce the risk of death and reinfarction (OR 0.78, 95% CI: 0.55-1.10, p=0.16), death (OR 0.77, 95% CI: 0.51-1.17, p=0.22), reinfarction (OR 0.79, 95% CI: 0.46-1.33, p=0.38) and stent thrombosis (OR 0.77, 95% CI: 0.43-1.35, p=0.36) as compared with intravenous administration. CONCLUSIONS: In STEMI patients undergoing primary PCI, intracoronary abciximab does not provide additional benefits as compared with standard intravenous treatment and, therefore, it should not be recommended as the default route of administration in this setting.

Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial.

BACKGROUND: If percutaneous coronary intervention (PCI) is required in patients taking oral anticoagulants, antiplatelet therapy with aspirin and clopidogrel is indicated, but such triple therapy increases the risk of serious bleeding. We investigated the safety and efficacy of clopidogrel alone compared with clopidogrel plus aspirin. METHODS: We did an open-label, multicentre, randomised, controlled trial in 15 centres in Belgium and the Netherlands. From November, 2008, to November, 2011, adults receiving oral anticoagulants and undergoing PCI were assigned clopidogrel alone (double therapy) or clopidogrel plus aspirin (triple therapy). The primary outcome was any bleeding episode within 1 year of PCI, assessed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769938. FINDINGS: 573 patients were enrolled and 1-year data were available for 279 (98·2%) patients assigned double therapy and 284 (98·3%) assigned triple therapy. Mean ages were 70·3 (SD 7·0) years and 69·5 (8·0) years, respectively. Bleeding episodes were seen in 54 (19·4%) patients receiving double therapy and in 126 (44·4%) receiving triple therapy (hazard ratio [HR] 0·36, 95% CI 0·26-0·50, p<0·0001). In the double-therapy group, six (2·2%) patients had multiple bleeding events, compared with 34 (12·0%) in the triple-therapy group. 11 (3·9%) patients receiving double therapy required at least one blood transfusion, compared with 27 (9·5%) patients in the triple-therapy group (odds ratio from Kaplan-Meier curve 0·39, 95% CI 0·17-0·84, p=0·011). INTERPRETATION: Use of clopiogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in the rate of thrombotic events. FUNDING: Antonius Ziekenhuis Foundation, Strect Foundation.

Multiple biomarkers for the prediction of short and long-term mortality after ST-segment elevation myocardial infarction: the Amsterdam Groningen collaboration.

Multiple biomarkers improve prognostication for long-term mortality in ST-segment elevation myocardial infarction (STEMI). However, one-third of mortality after STEMI occurs within initial discharge. Our objective was to determine whether multiple biomarkers (glucose, N-terminal pro-brain natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR)) predict both short-term as long-term mortality in STEMI. We used a patient-pooled dataset of consecutive STEMI patients, with complete biomarkers, who underwent primary percutaneous coronary intervention (PCI) in two single centers (Amsterdam and Groningen). With a previously developed multimarker risk score, based on three biomarkers, patients were indicated as low-, intermediate- or high risk. Cumulative 4-year mortality was estimated with the Kaplan-Meier method and compared with a log-rank test. We compared short-term and long-term mortality with a landmark set at 30 days because previous studies have shown that mortality largely occurs within 30 days. A total of 2,355 STEMI-patients were treated with primary PCI. The mortality rates in the low- (n = 1,531), intermediate- (n = 403) and high-risk (n = 421) groups were 4.8, 16.1, and 43.9 %, respectively. The differences were observed at a follow-up up to 30 days (log-rank p < 0.001) as well as after 30 days (log-rank p < 0.001). A multimarker risk score, based on admission levels of glucose, NT-proBNP, and eGFR identifies STEMI patients at low-, intermediate-, and high-risk for short-term and long-term mortality.

Percutaneous aortic valve replacement using a subclavian artery graft.

Over the past few years transcatheter heart valve implantation (THI) has become an alternative treatment for aortic valve replacement. The THI does not require a midline sternotomy or cardiopulmonary bypass and can be performed through a transfemoral or a transapical approach. In case of severe peripheral vascular disease the transapical route is usually chosen. However, when the use of a small anterolateral thoracotomy is not preferred due to comorbidities, the subclavian artery can be considered as a third alternative route. This case report describes an approach for THI through the subclavian artery, by using a Dacron graft.

Metformin in non-diabetic patients presenting with ST elevation myocardial infarction: rationale and design of the glycometabolic intervention as adjunct to primary percutaneous intervention in ST elevation myocardial infarction (GIPS)-III trial.

BACKGROUND: Left ventricular dysfunction and the development of heart failure is a frequent and serious complication of myocardial infarction. Recent animal experimental studies suggested that metformin treatment reduces myocardial injury and preserves cardiac function in non-diabetic rats after experimental myocardial infarction. We will study the efficacy of metformin with the aim to preserve left ventricular ejection fraction in non-diabetic patients presenting with ST elevation myocardial infarction (STEMI). METHODS: The Glycometabolic Intervention as adjunct to Primary percutaneous intervention in ST elevation myocardial infarction (GIPS)-III trial is a prospective, single center, double blind, randomized, placebo-controlled trial. Three-hundred-and-fifty patients, without diabetes, requiring primary percutaneous coronary intervention (PCI) for STEMI will be randomized to metformin 500 mg twice daily or placebo treatment and will undergo magnetic resonance imaging (MRI) after 4 months. Major exclusion criteria were prior myocardial infarction and severe renal dysfunction. The primary efficacy parameter is left ventricular ejection fraction 4 months after randomization. Secondary and tertiary efficacy parameters include major adverse cardiac events, new onset diabetes and glycometabolic parameters, and echocardiographic diastolic function. Safety parameters include renal function deterioration and lactic acidosis. CONCLUSIONS: The GIPS-III trial will evaluate the efficacy of metformin treatment to preserve left ventricular ejection fraction in STEMI patients without diabetes.

Clinical impact of intracoronary abciximab in patients undergoing primary percutaneous coronary intervention: an individual patient data pooled analysis of randomised studies.

OBJECTIVES: The aim of this study was to perform an individual patient-level pooled analysis of randomised trials, comparing intracoronary versus intravenous abciximab bolus use in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: Abciximab represents a cornerstone in the treatment of STEMI patients undergoing primary PCI. Intracoronary abciximab bolus administration has been proposed as an alternative strategy to the standard intravenous route. However, whether intracoronary abciximab effectively improves clinical outcomes compared with standard route remains unknown. METHODS: Individual data of 1198 patients enrolled in five trials were entered into the pooled analysis. The primary endpoint of the study was the occurrence of all-cause death and reinfarction at 30-day follow-up. Secondary endpoints were all-cause death, reinfarction and target-vessel revascularisation (TVR). RESULTS: No significant heterogeneity was found across trials. Compared with the intravenous route, intracoronary abciximab administration significantly reduced the risk of the composite of death and reinfarction (HR 0.52, 95% CI 0.29 to 0.94; p=0.03), death (HR 0.44, 95% CI 0.20 to 0.95; p=0.04) and TVR (HR 0.53, 95% CI 0.29 to 0.99; p=0.045), without a significant impact on the risk of reinfarction (HR 0.54, 95% CI 0.24 to 1.21; p=0.13). However, after correction for baseline differences, only the composite of death/reinfarction and death remained significant. CONCLUSIONS: In STEMI patients undergoing primary PCI, intracoronary abciximab administration, when compared with the intravenous standard route, can improve short-term clinical outcomes mainly by reducing the risk of death.

Inducible cardiac ischaemia is related to a decrease in the whole-blood Toll-like receptor 2 and 4 response.

TLR (Toll-like receptor) activation-induced inflammatory responses are important in the progression of atherosclerosis. We previously showed that TLR-dependent leucocyte responsiveness is acutely attenuated following percutaneous coronary intervention or vascular surgery. Furthermore, cytokine release following whole-blood TLR-2 and TLR-4 stimulation is negatively correlated with fractional flow reserve, suggesting that chronic ischaemia can elicit an enhanced inflammatory response. In the present study, we assessed the association between leucocyte TLR-2 and TLR-4 responsiveness and pre-existent and inducible ischaemia in patients undergoing SPECT (single-photon emission computed tomography)-MPI (myocardial perfusion imaging). TLR-2, TLR-4 and CD11b expression on monocytes were measured in blood samples that were obtained from 100 patients with suspected coronary artery disease before and after myocardial stress testing for SPECT-MPI. IL-8 (interleukin-8) levels were determined after whole-blood stimulation with Pam3Cys (TLR-2) and LPS (lipopolysaccharide; TLR-4). On the basis of SPECT-MPI, patients were categorized into three groups: reversible defect, irreversible defect and no defect. Myocardial stress induced a reduction in TLR-4 expression (2.46±0.21 compared with 2.17±0.16 arbitrary units, P=0.001) and CD11b expression (83.2±1.73 compared with 76.0±1.89 arbitrary units, P<0.001). TLR-induced IL-8 production before myocardial stress induction was not associated with the results of SPECT-MPI. However, a significant decrease in IL-8 production following TLR stimulation was observed after stress, which was more pronounced in patients with a reversible defect. In conclusion, inducible ischaemia is associated with a decrease in whole-blood TLR-2 and TLR-4 response. These results point to a regulating role of TLRs in order to prevent excessive inflammatory events known to occur during acute ischaemia.

Usefulness of thrombus aspiration for the treatment of coronary stent thrombosis.

Current treatment for coronary stent thrombosis (ST) often lacks satisfactory results and clinical outcome is poor. We investigated the impact of manual thrombus aspiration during percutaneous coronary intervention (PCI) on myocardial reperfusion and clinical outcome in patients with angiographically proved ST. We interrogated our PCI registry for patients with a first stent placement from January 2002 through May 2010 who had undergone an emergency repeated PCI procedure and systematically reviewed coronary angiograms and hospital records for evidence of ST. We identified 113 patients with ST. Thrombus aspiration was used in 51 patients and 62 patients received conventional PCI. Histopathologic analysis of thrombus aspirates was performed in 6 patients. Use of thrombus aspiration predicted postprocedure Thrombolysis In Myocardial Infarction grade 3 flow (odds ratio 3.16, 95% confidence interval 1.22 to 8.17, p = 0.018) and myocardial blush grade 2/3 (odds ratio 3.20, 95% confidence interval 1.20 to 8.55, p = 0.020) after multivariable adjustment with bootstrap model selection. Distal embolization was lower in the thrombus aspiration group compared to the conventional PCI group (14% vs 37%, p = 0.017). In most patients, aspirated thrombus was large and contained platelet and erythrocyte components at histopathologic analysis. Mortality in the thrombus aspiration group and conventional PCI group was 9.8% versus 16% at 30 days (p = 0.351) and 12% versus 21% at 1 year (p = 0.220), respectively. In conclusion, use of manual thrombus aspiration in patients with ST was associated with greater epicardial and microvascular myocardial reperfusion. In addition, mortality was lower in patients treated with thrombus aspiration, although not statistically significant.

Culprit vessel only versus multivessel and staged percutaneous coronary intervention for multivessel disease in patients presenting with ST-segment elevation myocardial infarction: a pairwise and network meta-analysis.

OBJECTIVES: The purposes of this study were to investigate whether, in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD), percutaneous coronary intervention (PCI) should be confined to the culprit or also nonculprit vessels and, when performing PCI for nonculprit vessels, whether it should take place during primary PCI or staged procedures. BACKGROUND: A significant percentage of STEMI patients have MVD. However, the best PCI strategy for nonculprit vessel lesions is unknown. METHODS: Pairwise and network meta-analyses were performed on 3 PCI strategies for MVD in STEMI patients: 1) culprit vessel only PCI strategy (culprit PCI), defined as PCI confined to culprit vessel lesions only; 2) multivessel PCI strategy (MV-PCI), defined as PCI of culprit vessel as well as ≥1 nonculprit vessel lesions; and 3) staged PCI strategy (staged PCI), defined as PCI confined to culprit vessel, after which ≥1 nonculprit vessel lesions are treated during staged procedures. Prospective and retrospective studies were included when research subjects were patients with STEMI and MVD undergoing PCI. The primary endpoint was short-term mortality. RESULTS: Four prospective and 14 retrospective studies involving 40,280 patients were included. Pairwise meta-analyses demonstrated that staged PCI was associated with lower short- and long-term mortality as compared with culprit PCI and MV-PCI and that MV-PCI was associated with highest mortality rates at both short- and long-term follow-up. In network analyses, staged PCI was also consistently associated with lower mortality. CONCLUSIONS: This meta-analysis supports current guidelines discouraging performance of multivessel primary PCI for STEMI. When significant nonculprit vessel lesions are suitable for PCI, they should only be treated during staged procedures.

Comparison of the temporal release pattern of copeptin with conventional biomarkers in acute myocardial infarction.

BACKGROUND: Early detection of acute myocardial infarction (AMI) using cardiac biomarkers of myocardial necrosis remains limited since these biomarkers do not rise within the first hours from onset of AMI. We aimed to compare the temporal release pattern of the C-terminal portion of provasopressin (copeptin) with conventional cardiac biomarkers, including creatine kinase isoenzyme (CK-MB), cardiac troponin T (cTnT), and high-sensitivity cTnT (hs-cTnT), in patients with ST-elevation AMI. METHODS: We included 145 patients undergoing successful primary percutaneous coronary intervention (PCI) for a first ST-elevation AMI presenting within 12 h of symptom onset. Blood samples were taken on admission and at four time points within the first 24 h after PCI. RESULTS: In contrast to all other markers, copeptin levels were already elevated on admission and were higher with a shorter time from symptom onset to reperfusion and lower systolic blood pressure. Copeptin levels peaked immediately after symptom onset at a maximum of 249 pmol/L and normalized within 10 h. In contrast, CK-MB, cTnT, and hs-cTnT peaked after 14 h from symptom onset at a maximum of 275 U/L, 5.75 µg/L, and 4.16 µg/L, respectively, and decreased more gradually. CONCLUSIONS: Copeptin has a distinct release pattern in patients with ST-elevation AMI, peaking within the first hour after symptom onset before conventional cardiac biomarkers and falling to normal ranges within the first day. Further studies are required to determine the exact role of copeptin in AMI suspects presenting within the first hours after symptom onset.

Circulating leukocyte and carotid atherosclerotic plaque telomere length: interrelation, association with plaque characteristics, and restenosis after endarterectomy.

OBJECTIVE: Shorter leukocyte telomeres are associated with atherosclerosis and predict future heart disease. The goal of the present study was to determine whether leukocyte telomere length is related to atherosclerotic plaque telomere length and whether it is associated with plaque characteristics or recurrence of disease. METHODS AND RESULTS: Telomere length was measured by real-time quantitative polymerase chain reaction in atherosclerotic plaques and leukocytes in patients with carotid atherosclerosis undergoing carotid endarterectomy (n=684) and of leukocytes in age- and gender-balanced subjects without clinical atherosclerosis (n=780). Leukocyte telomere length was shorter in patients versus controls (0.99 [interquartile range (IQR): 0.79 to 1.26] versus 1.06 [0.80 to 1.39]; P=0.0007). Plaque telomeres were longer than leukocyte telomeres (1.42 [IQR: 1.21 to 1.77] versus 1.01 [IQR: 0.75 to 1.34]; P<1.00×10(-6)) and independent of age. Leukocyte and plaque telomere length were only weakly correlated (correlation coefficient r2=0.04, P=0.03). Patients, whose plaques showed marked macrophage infiltration and large lipid core, had longer plaque telomeres (1.61 [IQR: 1.32 to 2.04] versus 1.40 [IQR: 1.15 to 1.57]; P=0.006) and shorter leukocyte telomeres (0.88 [IQR: 0.75 to 1.20] versus 1.03 [IQR: 0.83 to 1.34]; P=0.02). Plaque telomere length was associated with restenosis 1 year after endarterectomy (OR 1.58±0.206; P=0.026 per SD decrease of plaque telomere length). CONCLUSIONS: Leukocyte telomere length is associated with the presence of atherosclerotic carotid plaques but is not a proxy for local plaque telomere length. Plaque telomere length is related to plaque characteristics and development of restenosis following endarterectomy.