The value of computed tomography for head trauma in patients presenting with out-of-hospital cardiac arrest before emergency percutaneous coronary intervention.

INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) caused by an ST-elevation myocardial infarction (STEMI) is often accompanied by a sudden loss of consciousness that may cause the patient to collapse with resulting head trauma, leading to a suspicion of possible intracranial haemorrhage. To rule out intracranial haemorrhage before emergency percutaneous coronary intervention (PCI), emergency computed tomography (CT) of the head might be useful but also causes a delay in percutaneous STEMI treatment. METHODS: The medical records of all adult patients that presented with OHCA to the emergency department (ED) of the University Medical Centre Utrecht (UMCU), the Netherlands between 16 February 2020 and 16 February 2022 were reviewed. RESULTS: A total of 263 patients presented to the ED with an OHCA; 50 presented with a STEMI requiring emergency PCI. Thirty-nine (78%) patients with a STEMI were immediately referred to the catheterisation laboratory and 11 (22%) STEMI patients underwent a CT scan prior to emergency angiography; in no case was PCI deferred on the basis of the CT findings. The dominant indication for CT of the head was collapse, reported by 10 patients and resulting in a visible traumatic head injury in 7 patients. In none of the patients was intracranial haemorrhage detected. However, there was a delay between presentation to the ED and arrival at the catheterisation laboratory in patients who underwent CT of the head (mean 63 ± 25 min) before emergency PCI compared to patients without a CT scan (mean 37 ± 21 min). CONCLUSION: CT of the head did not result in a diagnosis of intracranial haemorrhage or deferral of PCI but did delay PCI treatment for STEMI in patients presenting with OHCA.

Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (CPR) restores perfusion and oxygenation in a patient who does not have spontaneous circulation. The evidence with regard to the effect of extracorporeal CPR on survival with a favorable neurologic outcome in refractory out-of-hospital cardiac arrest is inconclusive. METHODS: In this multicenter, randomized, controlled trial conducted in the Netherlands, we assigned patients with an out-of-hospital cardiac arrest to receive extracorporeal CPR or conventional CPR (standard advanced cardiac life support). Eligible patients were between 18 and 70 years of age, had received bystander CPR, had an initial ventricular arrhythmia, and did not have a return of spontaneous circulation within 15 minutes after CPR had been initiated. The primary outcome was survival with a favorable neurologic outcome, defined as a Cerebral Performance Category score of 1 or 2 (range, 1 to 5, with higher scores indicating more severe disability) at 30 days. Analyses were performed on an intention-to-treat basis. RESULTS: Of the 160 patients who underwent randomization, 70 were assigned to receive extracorporeal CPR and 64 to receive conventional CPR; 26 patients who did not meet the inclusion criteria at hospital admission were excluded. At 30 days, 14 patients (20%) in the extracorporeal-CPR group were alive with a favorable neurologic outcome, as compared with 10 patients (16%) in the conventional-CPR group (odds ratio, 1.4; 95% confidence interval, 0.5 to 3.5; P = 0.52). The number of serious adverse events per patient was similar in the two groups. CONCLUSIONS: In patients with refractory out-of-hospital cardiac arrest, extracorporeal CPR and conventional CPR had similar effects on survival with a favorable neurologic outcome. (Funded by the Netherlands Organization for Health Research and Development and Maquet Cardiopulmonary [Getinge]; INCEPTION ClinicalTrials.gov number, NCT03101787.).

Long-term follow-up of contemporary drug-eluting stent implantation in diabetic patients: Subanalysis of a randomized controlled trial.

OBJECTIVE: The elevated risk of adverse events following percutaneous coronary intervention in diabetic patients persists with newer-generation DES. The polymer-free amphilimus-eluting stent (PF-AES) possesses characteristics with a potentially enhanced performance in patients with diabetes. Data from the 1-year follow-up period has been previously published. The aim of this subanalysis was to assess long-term performance of two contemporary drug-eluting stents (DES) in a diabetic population. METHODS: In the ReCre8 trial, patients were stratified for diabetes and troponin status, and randomized to implantation of a permanent polymer zotarolimus-eluting stent (PP-ZES) or PF-AES. The primary endpoint was target-lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization. Clinical outcomes between discharge and 3 years follow-up were assessed. RESULTS: A total of 302 patients with diabetes were included in this analysis. After 3 years, TLF occurred in 12.5% of PP-ZES patients versus 10.0% in PF-AES patients (p = 0.46). Similarly, the separate components of TLF were comparable between the two study arms. The secondary composite endpoint of NACE was higher in the PP-ZES arm with 45 cases (29.6%) versus 30 cases (20.0%) in the PF-AES arm (p = 0.036). In the insulin-dependent diabetic population, TLF occurred in 19.1% of PP-ZES patients versus 10.4% of PF-AES patients (p = 0.21). NACE occurred in 40.4% of PP-ZES patients versus 27.1% of PF-AES patients (p = 0.10). CONCLUSIONS: This subanalysis shows that the use of PF-AES results in similar clinical outcomes as compared to PP-ZES, yet some benefits of use of PF-AES in diabetic patients may prevail. Future dedicated trials should confirm these findings.

Clinical outcomes after permanent polymer or polymer-free stent implantation in patients with diabetes mellitus: The ReCre8 diabetes substudy.

OBJECTIVES: The purpose of this analysis was to compare target-lesion failure (TLF) of a permanent polymer zotarolimus-eluting stent (PP-ZES) versus a polymer-free amphilimus-eluting stent (PF-AES) in diabetics. BACKGROUND: The improvement of outcomes with new-generation drug-eluting stent as seen in the general population is less pronounced among diabetics. The PF-AES introduces an elution-technology with potential enhanced performance in diabetics. METHODS: In this subanalysis of the ReCre8 trial, patients were randomized to either a PP-ZES or PF-AES after stratification for diabetes and troponin status. The primary device-oriented endpoint was TLF, a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization. RESULTS: In the ReCre8 trial, 304 (20%) patients were diabetic and 96 (6%) had insulin-dependent diabetes mellitus. There was no statistically significant difference between the two study arms regarding the primary endpoint (PP-ZES 7.2% vs. PF-AES 4.0%; p = .21), although the composite of net adverse clinical events was higher in the PP-ZES arm (15.7 vs. 8.0%; p = .035). Stent thrombosis was low in both groups with no cases in the PP-ZES arm and 1 case in the PF-AES arm (p = .32). Regarding insulin-treated diabetics, TLF was higher in the PP-ZES arm (14.9 vs. 2.1%; p = .022). CONCLUSIONS: Diabetics could potentially benefit from a dedicated stent, releasing sirolimus with a lipophilic carrier (amphilimus-formulation). Future trials should confirm the potential benefit of a PF-AES in this population.

High bleeding risk in patients undergoing percutaneous coronary intervention with drug-eluting stent implantation: ReCre8 subanalysis.

Objectives: In an all-comers cohort undergoing percutaneous coronary intervention (PCI), we aimed to assess prevalence of high bleeding risk (HBR) patients and impact of HBR and dual antiplatelet therapy (DAPT) on clinical events. Background: HBR represents a complex subgroup of patients undergoing PCI. Methods: In the ReCre8 trial, patients undergoing PCI were stratified for troponin status and diabetes and randomized to a permanent polymer zotarolimus-eluting- or polymer-free amphilimus-eluting stent. Patients were treated with 12 months (troponin-positive) or one month (troponin-negative) of DAPT. We evaluated clinical outcomes in patients with and without HBR according to the Academic Research Consortium for High Bleeding Risk criteria. Results: From a total of 1488 patients included in this subanalysis, 406 patients (27.3 %) were identified as being at HBR. Among HBR patients, target-lesion failure (TLF) was similar after one year yet was higher after three years (13.3 % vs. 9.1 %; p = 0.013), compared to non-HBR patients. There was no difference in Bleeding Academic Research Consortium (BARC) 3 to 5 bleeding, however BARC 2 to 5 bleeding was higher after three years with 4.9 % vs. 3.0 % (p = 0.037). There were no differences between troponin-positive (12-months DAPT) and -negative (1-month DAPT) HBR patients with respect to ischemic and bleeding outcomes. Conclusions: In this all-comers population of PCI patients, a higher TLF rate among HBR patients at long-term follow-up was found, underlining the complexities involving treatment of HBR patients. We did not observe statistically significant differences in BARC 3 to 5 bleeding between HBR and non-HBR patients regardless of DAPT duration. Clinical trial registration: URL: http://www.clinicaltrials.gov, unique identifier: NCT02328898.

3-Year Clinical Outcomes After Implantation of Permanent-Polymer Versus Polymer-Free Stent: ReCre8 Landmark Analysis.

OBJECTIVES: The aim of this analysis was to assess long-term clinical outcomes of the polymer-free Amphilimus-eluting stent (PF-AES) compared with a latest generation permanent-polymer drug-eluting stent (DES) in an all-comers population. BACKGROUND: PF-AES possess multiple properties improving targeted drug elution without the presence of polymers. Evaluation of long-term clinical performance of PF-AES versus latest generation permanent-polymer DES has not yet been performed in a large randomized trial introducing shortened dual-antiplatelet therapy. METHODS: In this physician-initiated, multicenter, randomized, all-comers trial, patients undergoing percutaneous coronary intervention with implantation of DES were enrolled. Patients were stratified for diabetes and troponin status and randomized to implantation of a permanent-polymer zotarolimus-eluting stent (PP-ZES) or a PF-AES. Dual-antiplatelet therapy duration was 12 months in troponin-positive patients and 1 month in troponin-negative patients. A noninferiority analysis was conducted to compare the 2 arms regarding target lesion failure (TLF) between 1 and 3 years. RESULTS: A total of 1,491 patients were randomized and treated. In this landmark analysis, between 1- and 3-year follow-up, TLF occurred in 35 patients (4.9%) in the PP-ZES arm and 37 PF-AES patients (5.1%). Clinical noninferiority of the PF-AES was confirmed, with a risk difference of 0.2% (upper limit 1-sided 95% CI: 2.2%; Pnoninferiority = 0.0031). CONCLUSIONS: ReCre8 (Randomized "All-Comer" Evaluation of a Permanent Polymer Resolute Integrity Stent Versus a Polymer Free Cre8 Stent) is the first randomized, multicenter trial with a head-to-head comparison of PP-ZES compared with PF-AES to investigate clinical outcomes of these new-generation DES in an all-comers population with long-term follow-up. On the basis of the present results, PF-AES are clinically noninferior to PP-ZES regarding TLF between 1 and 3 years. (Randomized "All-Comer" Evaluation of a Permanent Polymer Resolute Integrity Stent Versus a Polymer Free Cre8 Stent; NCT02328898).

Early initiation of extracorporeal life support in refractory out-of-hospital cardiac arrest: Design and rationale of the INCEPTION trial.

Return of spontaneous circulation occurs in less than 10% of patients with cardiac arrest undergoing cardiopulmonary resuscitation (CPR) for more than 15 minutes. Studies suggest that extracorporeal life support during cardiopulmonary resuscitation (ECPR) improves survival rate in these patients. These studies, however, are hampered by their non-randomized, observational design and are mostly single-center. A multicenter, randomized controlled trial is urgently warranted to evaluate the effectiveness of ECPR. HYPOTHESIS: We hypothesize that early initiation of ECPR in refractory out-of-hospital cardiac arrest (OHCA) improves the survival rate with favorable neurological status. STUDY DESIGN: The INCEPTION trial is an investigator-initiated, prospective, multicenter trial that will randomly allocate 110 patients to either continued CPR or ECPR in a 1:1 ratio. Patients eligible for inclusion are adults (≤ 70 years) with witnessed OHCA presenting with an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT), who received bystander basic life support and who fail to achieve sustained return of spontaneous circulation within 15 minutes of cardiopulmonary resuscitation by emergency medical services. The primary endpoint of the study is 30-day survival rate with favorable neurological status, defined as 1 or 2 on the Cerebral Performance Category score. The secondary endpoints include 3, 6 and 12-month survival rate with favorable neurological status and the cost-effectiveness of ECPR compared to CCPR. SUMMARY: The INCEPTION trial aims to determine the clinical benefit for the use of ECPR in patients with refractory OHCA presenting with VF/VT. Additionally, the feasibility and cost-effectiveness of ECPR will be evaluated.

One-year clinical outcomes of patients treated with polymer-free amphilimus-eluting stents or zotarolimus-eluting stents: A propensity-score adjusted analysis.

BACKGROUND: Polymer-free amphilimus-eluting stents (PF-AES) represent a novel elution-technology in coronary stenting. We aimed to assess 1-year clinical outcomes of PF-AES as compared to latest-generation permanent polymer zotarolimus-eluting stents (PP-ZES) in a real-world all-comers setting. METHODS: A prospective registry of patients treated with either PF-AES or PP-ZES between 2014 and 2016 was conducted. The primary outcome was defined as major adverse cardiac and cerebrovascular events (MACCE), and the secondary outcome was defined as target-lesion failure (TLF) at 1 year. To account for measured confounders, a propensity-score adjusted Cox proportional-hazard model was built to evaluate clinical outcomes. RESULTS: A total of 734 consecutive patients with 1,269 DES implantations were enrolled. The population was characterized by 28% diabetes, 24% ST-segment elevation myocardial infarction, and a high number of complex lesions (69%). The rate of MACCE was 11.5% for PF-AES and 13.6% for PP-ZES, plog-rank = 0.11. TLF was numerically lower in PF-AES as compared to PP-ZES (5.4 vs. 6.1%, plog-rank = 0.68). After propensity-score adjustment, PF-AES showed a trend toward a lower rate of MACCE and a favorable rate of TLF as compared to PP-ZES (HR 0.70; 95%CI 0.45 to 1.10, P = 0.12; and HR 0.88; 95%CI 0.47 to 1.65, P = 0.68, respectively). Rates of definite ST were low (0.8 vs. 0.3%, plog-rank = 0.62). CONCLUSIONS: Our study suggests that implantation of PF-AES was safe and effective in real-world patients, with low-rates of MACCE and TLF at 1 year. Our data needs to be confirmed by a large trial to evaluate the clinical outcomes of this novel polymer-free, eluting-technology used in PF-AES.

Randomized All-Comers Evaluation of a Permanent Polymer Zotarolimus-Eluting Stent Versus a Polymer-Free Amphilimus-Eluting Stent.

BACKGROUND: Polymer-free amphilimus-eluting stents (PF-AES) represent a novel elution technology in the current era of drug-eluting stents. The clinical safety and efficacy of PF-AES as compared with latest-generation permanent-polymer zotarolimus-eluting stents (PP-ZES) have not yet been investigated in a large randomized trial. METHODS: In this physician-initiated, prospective, multicenter, randomized, noninferiority trial, an all-comers population requiring percutaneous coronary intervention was enrolled across 3 European sites. Randomization (1:1 ratio) to PP-ZES or PF-AES was performed after stratification for troponin status and diabetes mellitus. In both treatment arms, troponin-positive patients were planned for 12-month dual antiplatelet therapy, whereas troponin-negative patients were planned for 1-month dual antiplatelet therapy. Outcome assessors were blinded to the allocated treatment. The device-oriented primary end point of target-lesion failure was defined as cardiac death, target-vessel myocardial infarction, or target-lesion revascularization at 12-months as analyzed by modified intention-to-treat (80% power, and a 3.5% noninferiority margin). RESULTS: In total, 1502 patients were randomized and 1491 treated with the assigned stent and available for follow-up. The primary end point occurred in 42 (5.6%) of the 744 patients receiving PP-ZES versus 46 (6.2%) of the 747 patients receiving PF-AES. PF-AES were clinically noninferior to PP-ZES (risk difference, 0.5%; upper limit 1-sided 95% confidence interval, 2.6%; Pnoninferiority=0.0086). Cardiac death occurred in 10 (1.3%) versus 10 patients (1.3%; P value for difference, 1.00), target-vessel myocardial infarction occurred in 18 (2.4%) versus 17 patients (2.3%; P value for difference, 0.87), and target-lesion revascularization occurred in 22 (2.9%) versus 20 patients (2.6%; P value for difference, 0.75) for PF-AES as compared with PP-ZES. Overall, definite or probable stent thrombosis occurred in 1.0%. CONCLUSIONS: PF-AES were noninferior to PP-ZES regarding target-lesion failure at 12 months. Findings regarding the secondary end point and prespecified subgroups were generally consistent with that of the primary end point. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02328898.

Rationale and design of amphilimus sirolimus-eluting stents versus zotarolimus-eluting stents in all-comers requiring percutaneous coronary intervention (ReCre8): A multicenter randomized clinical trial.

BACKGROUND: Amphilimus sirolimus-eluting stents (A-SES) represent a novel elution technology in the current era of drug-eluting stents with promising results in patients with diabetes mellitus. At present no large trial has been designed to evaluate clinical outcomes of A-SES as compared to new-generation drug-eluting stents in unselected patients. Accordingly, we designed this trial to evaluate clinical noninferiority of A-SES as compared with zotarolimus-eluting stents (ZES) in a real-world, all-comers setting. STUDY DESIGN: ReCre8 is a prospective multicenter randomized clinical trial evaluating the clinical outcomes of A-SES as compared with ZES in all-comers requiring percutaneous coronary intervention. Patients are randomized 1:1 to receive either A-SES or ZES. On-site block-randomization is stratified by diabetes mellitus, and troponin status to perform prespecified subanalyses. Patients receive 1-month of dual antiplatelet therapy (DAPT) when troponin-negative, or 12-months of DAPT when troponin-positive. The primary endpoint is target-lesion failure at 1-year follow-up. A total of 1,532 patients will be enrolled to demonstrate clinical noninferiority of A-SES with at least 80% power, a noninferiority margin of 3.5% and a type-I-error of 0.05. CONCLUSIONS: ReCre8 (NCT02328898) is the first randomized multicenter trial with a head-to-head comparison of A-SES as compared with ZES to investigate the clinical safety and efficacy of these new-generation DES in a real-world, all-comers population.

Clinical outcomes of complex real-world diabetic patients treated with amphilimus sirolimus-eluting stents or zotarolimus-eluting stents: A single-center registry.

OBJECTIVE: To assess clinical outcomes of Amphilimus Sirolimus-Eluting Stents (A-SES) as compared to Zotarolimus-Eluting Stents (ZES) in complex real-world diabetic patients. BACKGROUND: Patients with diabetes mellitus represent one of the most challenging scenarios with high rates of restenosis and stent thrombosis in the current era of drug-eluting stents. Hence, we assessed the safety of A-SES versus ZES in complex diabetic patients. METHODS: In this observational study, we analyzed all consecutive patients with diabetes mellitus referred to our center from November 2012 to November 2014. The primary outcome was target-lesion failure at 1-year follow-up. RESULTS: A total of 165 consecutive diabetic patients underwent percutaneous coronary intervention with A-SES or ZES for stable coronary artery disease in our tertiary center. Using the Kaplan Meier method the cumulative incidence of target-lesion failure was 6.7% (5.9% A-SES versus 7.5% ZES, p=0.19) at 1-year follow-up. Event-free survival at 1year follow-up was similar (89.4% A-SES vs. 83.3% ZES, p=0.29). Interestingly, we did not find any cases of definite-, and only one case of probable stent thrombosis in this high risk cohort. CONCLUSION: In this real-world registry, A-SES and ZES seems to be associated with promising 1-year clinical safety outcomes following PCI in a contemporary cohort of high-risk diabetic patients. Our results should be considered hypothesis generating, as the clinical safety of A-SES has to be confirmed in a large trial.

Inter-Ethnic Differences in Quantified Coronary Artery Disease Severity and All-Cause Mortality among Dutch and Singaporean Percutaneous Coronary Intervention Patients.

BACKGROUND: Coronary artery disease (CAD) is a global problem with increasing incidence in Asia. Prior studies reported inter-ethnic differences in the prevalence of CAD rather than the severity of CAD. The angiographic "synergy between percutaneous coronary intervention (PCI) with taxus and cardiac surgery" (SYNTAX) score quantifies CAD severity and predicts outcomes. We studied CAD severity and all-cause mortality in four globally populous ethnic groups: Caucasians, Chinese, Indians and Malays. METHODS: We quantified SYNTAX scores of 1,000 multi-ethnic patients undergoing PCI in two tertiary hospitals in the Netherlands (Caucasians) and Singapore (Chinese, Indians and Malays). Within each ethnicity we studied 150 patients with stable CAD and 100 with ST-elevated myocardial infarction (STEMI). We made inter-ethnic comparisons of SYNTAX scores and all-cause mortality. RESULTS: Despite having a younger age (mean age Indians: 56.8 and Malays: 57.7 vs. Caucasians: 63.7 years), multivariable adjusted SYNTAX scores were significantly higher in Indians and Malays than Caucasians with stable CAD: 13.4 [11.9-14.9] and 13.4 [12.0-14.8] vs. 9.4 [8.1-10.8], p<0.001. Among STEMI patients, SYNTAX scores were highest in Chinese and Malays: 17.7 [15.9-19.5] and 18.8 [17.1-20.6] vs. 15.5 [13.5-17.4] and 12.7 [10.9-14.6] in Indians and Caucasians, p<0.001. Over a median follow-up of 709 days, 67 deaths (stable CAD: 37, STEMI: 30) occurred. Among STEMI patients, the SYNTAX score independently predicted all-cause mortality: HR 2.5 [1.7-3.8], p<0.001 for every 10-point increase. All-cause mortality was higher in Indian and Malay STEMI patients than Caucasians, independent of SYNTAX score (adjusted HR 7.2 [1.5-34.7], p=0.01 and 5.8 [1.2-27.2], p=0.02). CONCLUSION: Among stable CAD and STEMI patients requiring PCI, CAD is more severe in Indians and Malays than in Caucasians, despite having a younger age. Moreover, Indian and Malay STEMI patients had a greater adjusted risk of all-cause mortality than Caucasians, independent of SYNTAX score.

Severity of stable coronary artery disease and its biomarkers differ between men and women undergoing angiography.

BACKGROUND: Coronary artery disease (CAD) affects both men and women. Cardiovascular biomarkers have been suggested to relate to CAD severity, but data on sex-specificity is scarce. Therefore, we investigated the association of established biomarkers with the severity of CAD in stable patients undergoing coronary angiography in a sex-specific manner. METHODS: We studied stable patients undergoing coronary angiography and measured CAD severity by SYNTAX score and biomarker levels (N-terminal pro-brain natriuretic peptide (NT pro-BNP), high-sensitivity CRP (hsCRP), cystatin C (CysC), myeloperoxidase (MPO), high-sensitivity troponin I (hsTnI) and von Willebrand factor (VWF)). We tested for sex differences in SYNergy between percutaneous coronary intervention with TAXUS™ and cardiac surgery (SYNTAX) scores and biomarker levels using multivariable ANCOVA. We investigated the association of biomarker levels with SYNTAX score in a multivariable linear regression with interaction terms for sex. RESULTS: We analysed data on 460 men and 175 women. SYNTAX scores were significantly lower in women (9.99 points vs. 11.88 points). Univariably, hsCRP and hsTnI levels were significantly associated with SYNTAX scores (both ß 2.5). In multivariable analysis only hsCRP associated with SYNTAX score (ß 1.9, p = 0.009). Sex did not modify the association of biomarkers with SYNTAX score. CONCLUSION: CAD severity as quantified by SYNTAX score is lower in women than men based on coronary angiography. The association of biomarkers with CAD severity did not differ between the sexes.

Clinical and angiographic predictors and prognostic value of failed thrombus aspiration in primary percutaneous coronary intervention.

OBJECTIVES: This study sought to investigate which factors are associated with failure of thrombus aspiration (TA) and if this has prognostic implications. BACKGROUND: The pathophysiological mechanism and clinical benefit of TA during primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction is still in debate. METHODS: Between August 2001 and October 2007, TA was attempted in 1,399 patients. Failure of TA was defined as the inability to reach and/or cross the occlusion with the aspiration catheter for effective thrombus removal. In addition, we analyzed patients in which no material could be obtained. We examined baseline clinical and angiographic variables related to failure of TA or to the lack of aspirate. Follow-up on vital status was obtained at 1 year. RESULTS: In 144 (10.3%) patients, the aspiration catheter failed to cross the lesion. After multivariable adjustment, marked proximal tortuosity (odds ratio [OR]: 2.88, 95% confidence interval [CI]: 1.92 to 4.31, p < 0.001), the presence of a calcified lesion (OR: 2.70, 95% CI: 1.77 to 4.13, p < 0.001), and a bifurcation lesion (OR: 1.97, 95% CI: 1.15 to 3.37, p = 0.013) were independent predictors of failed TA. Age over 60 years and the circumflex as infarct-related artery were associated with the lack of aspirate. Mortality rates at 1 year were 6.2% in patients with failed TA and 6.4% with successful TA (hazard ratio: 0.98, 95% CI: 0.49 to 1.95, p = 0.95). CONCLUSIONS: The presence of marked proximal tortuosity of the infarct-related artery, a calcified lesion, and a bifurcation lesion are independent predictors of failure of thrombus aspiration. We found that unsuccessful TA did not affect 1-year mortality.

Toll-like receptor 4 gene polymorphisms show no association with the risk of clinical or angiographic restenosis after percutaneous coronary intervention.

OBJECTIVE: Restenosis after percutaneous coronary intervention (PCI) remains an issue even in the drug-eluting stent era. Genetic polymorphisms may provide insight in the pathogenesis of restenosis and may help in the stratification of patients at risk for restenosis. The aim of this study was to examine whether polymorphisms at the toll-like receptor 4 (TLR4) locus, that are associated with impaired innate immune system and with an increased risk of cardiovascular events, were associated with clinical and/or angiographic restenosis after PCI. METHODS: The GENetic Determinants of Restenosis (GENDER) project was a prospective, multicenter study that enrolled 3146 consecutive patients after successful PCI. Frequencies of the TLR4 896A/G (Asp299Gly; rs4986790) and 1196C/T (Thr399Ile; rs4986791) polymorphisms and haplotypes were assessed. Patients were followed up for 1 year and in a subgroup of 406 patients angiographic follow-up was obtained. RESULTS: We included a total of 2682 patients that underwent successful PCI. There was no association between genotypes and the risk of target vessel revascularization at 1-year or late luminal loss at 6-months angiographic follow-up (P=0.53 and 0.44, respectively). Absence of association with target lesion revascularization and late luminal loss was replicated in the GEnetic risk factors for In-Stent Hyperplasia study Amsterdam (GEISHA) cohort study of 674 patients and in a subgroup of 550 patients with angiographic follow-up available (P=0.26, and 0.86, respectively). Moreover, in both the studies, no significant differences between haplotypes A/C and G/T were observed for target vessel revascularization at late luminal loss. CONCLUSION: Although inflammation has been implicated in the pathophysiology of restenosis, the 896A/G and 1196C/T polymorphisms or haplotypes based on these polymorphisms at the TLR4 locus are not associated with an increased risk of target vessel revascularization or angiographic restenosis after PCI. These polymorphisms are not useful for pre-PCI identification of patients at risk for restenosis.

Long-term follow-up after nonurgent percutaneous coronary intervention in unprotected left main coronary arteries.

OBJECTIVES: To evaluate the long-term outcomes of the selected patients by the local Heart Team to undergo percutaneous coronary intervention (PCI) of unprotected left main coronary artery (ULMCA) stenosis and to compare patients considered at low surgical risk versus at high surgical risk for coronary artery bypass grafting (CABG). BACKGROUND: CABG is recommended in patients with ULMCA stenosis according to the AHA/ACC and ESC guidelines, and there are limited data on the long-term outcomes in patients selected by the local Heart Team to undergo PCI. METHODS: Between 1996 and 2007, 227 patients underwent PCI for ULMCA stenosis based on decision of the local Heart Team and patient's and/or physician's preference. All patients were contacted at 1 year and in November 2008. RESULTS: Long-term follow-up was up to 8 years with a mean of 3.9 +/- 2.6 years. Overall, the Kaplan-Meier estimate of the composite of cardiac death, myocardial infarction (MI), or target lesion revascularization (TLR) was 14.8% at 1 year, 18.3% at 3 years, and 20.9% at 5 years with no events occurring thereafter. Patients considered at low surgical risk for CABG had a significantly lower incidence of cardiac death or MI compared to patients considered at high surgical risk at 8 years (1.4 vs. 16.8%; 1.4 vs. 14.8%, respectively); however, no significant difference was observed for cardiac death, MI, or TLR (18.6 vs. 24.4%). CONCLUSIONS: PCI of ULMCA stenosis in patients selected by the Heart Team resulted in good long-term clinical outcomes with most events occurring within the 1st year. Patients considered at low surgical risk for CABG have a significantly better long-term survival than patients at high risk for surgery.

Relationship of thrombus healing to underlying plaque morphology in sudden coronary death.

OBJECTIVES: The aim of this study was to assess differences in thrombus healing between ruptured and eroded plaques, given the natural difference in lesion substrate and that thrombi might exist days to weeks before the presentation of sudden coronary death. BACKGROUND: Although the ability to distinguish ruptures and erosions remains a major clinical challenge, in-hospital patients dying with acute myocardial infarction establish that erosions account for 25% of all deaths, where women experience a higher incidence compared with men. METHODS: Coronary lesions with thrombi (ruptures, n = 65; erosions, n = 50) received in consultation from the Medical Examiner's Office from 111 sudden death victims were studied. Thrombus healing was classified as early (<1 day) or late stage characterized in phases of lytic (1 to 3 days), infiltrating (4 to 7 days), or healing (>7 days). Morphometric analysis included vessel dimensions, necrotic core size, and macrophage density. RESULTS: Late-stage thrombi were identified in 79 of 115 (69%) culprit plaques. Women more frequently had erosion with a greater prevalence of late-stage thrombi (44 of 50, 88%) than ruptures (35 of 65, 54%, p < 0.0001). The internal elastic lamina area and percent stenosis were significantly smaller in erosions compared with ruptures (p < 0.0001 and p = 0.02), where plaque burden was greater (p = 0.008). Although macrophage infiltration in erosions was significantly less than ruptures (p = 0.03), there was no established relationship with thrombus organization. Other parameters of thrombus length and occlusive versus nonocclusive showed no association with healing. CONCLUSIONS: Approximately two-thirds of coronary thrombi in sudden coronary deaths are organizing, particularly in young individuals-especially women, who perhaps might require a different strategy of treatment.

p27kip1-838C>A single nucleotide polymorphism is associated with restenosis risk after coronary stenting and modulates p27kip1 promoter activity.

BACKGROUND: The cyclin-dependent kinase inhibitor p27(kip1) is a key regulator of smooth muscle cell and leukocyte proliferation in vascular disease, including in-stent restenosis. We therefore hypothesized that common genetic variations or single nucleotide polymorphisms in p27(kip1) may serve as a useful tool in risk stratification for in-stent restenosis. METHODS AND RESULTS: Three single nucleotide polymorphisms concerning the p27(kip1) gene (-838C>A, rs36228499; -79C>T, rs34330; +326G>T, rs2066827) were determined in a cohort of 715 patients undergoing coronary angioplasty and stent placement. We discovered that the p27(kip1)-838C>A single nucleotide polymorphism is associated with clinical in-stent restenosis; the -838AA genotype decreases the risk of target vessel revascularization (hazard ratio, 0.28; 95% confidence interval, 0.10 to 0.77). This finding was replicated in another cohort study of 2309 patients (hazard ratio, 0.61; 95% confidence interval, 0.40 to 0.93). No association was detected between this end point and the p27(kip1)-79C>T and +326G>T single nucleotide polymorphisms. We subsequently studied the functional importance of the -838C>A single nucleotide polymorphism and detected a 20-fold increased basal p27(kip1) transcriptional activity of the -838A allele containing promoter. CONCLUSIONS: Patients with the p27(kip1)-838AA genotype have a decreased risk of in-stent restenosis corresponding with enhanced promoter activity of the -838A allele of this cell-cycle inhibitor, which may explain decreased smooth muscle cell proliferation.

Histopathological features of aspirated thrombi after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction.

BACKGROUND: Plaque disruption with superimposed thrombus is the predominant mechanism responsible for the onset of acute coronary syndromes. Studies have shown that plaque disruption and thrombotic occlusion are frequently separated in time. We established the histopathological characteristics of material aspirated during primary percutaneous coronary intervention (PCI) in a large consecutive ST-elevation myocardial infarction (STEMI) population. METHODOLOGY/PRINCIPAL FINDINGS: Thrombus aspiration during primary PCI was performed in 1,362 STEMI patients. Thrombus age was classified as fresh (<1 day), lytic (1-5 days), or organized (>5 day). Further, the presence of plaque was documented. The histopathological findings were related to the clinical, angiographic, and procedural characteristics. Material could be aspirated in 1,009 patients (74%). Components of plaque were found in 395 of these patients (39%). Fresh thrombus was found in 577 of 959 patients (60%) compared to 382 patients (40%) with lytic or organized thrombi. Distal embolization was present in 21% of patients with lytic thrombus compared to 12% and 15% of patients with fresh or organized thrombus. CONCLUSIONS/SIGNIFICANCE: Material could be obtained in 74% of STEMI patients treated with thrombus aspiration during primary PCI. In 40% of patients thrombus age is older than 24 h, indicating that plaque disruption and thrombus formation occur significantly earlier than the onset of symptoms in many patients.

Presence of older thrombus is an independent predictor of long-term mortality in patients with ST-elevation myocardial infarction treated with thrombus aspiration during primary percutaneous coronary intervention.

BACKGROUND: Routine thrombus aspiration is frequently used during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction to prevent distal embolization. Recently, evidence of clinical benefit was published. In 50% of the ST-elevation myocardial infarction patients with an onset of symptoms <12 hours before, thrombi were shown to be >1 day old. This observation illustrates that plaque rupture and coronary occlusion are significantly separated in time. In the present study, we correlate the presence of fresh versus older thrombus with long-term mortality. METHODS AND RESULTS: Thrombus aspiration was performed in 1315 patients treated with primary percutaneous coronary intervention with 3 devices (Rescue, Export, and Proxis). Aspirated material was fixed in formalin and processed for histopathology. If possible, thrombus age was classified as either fresh only (<1 day) or older (>1 day). We identified fresh thrombus in 552 patients and older thrombus in 372 patients. The cumulative Kaplan-Meier estimate of all-cause mortality at 4 years was significantly higher in patients with older thrombus (16.0%) compared with patients with fresh thrombus (7.4%), with a hazard ratio of 1.82 (95% confidence interval, 1.17 to 2.85; P=0.008). Multivariate analysis identified the presence of older thrombus, in addition to other established predictors, as an independent predictor (hazard ratio, 1.83; 95% confidence interval, 1.14 to 2.93; P=0.01) of long-term mortality. CONCLUSIONS: Our study demonstrates that the presence of older thrombus, in addition to other established predictors, is an independent predictor of long-term mortality in patients with ST-elevation myocardial infarction treated with thrombus aspiration during primary percutaneous coronary intervention.