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Iron deficiency has been extensively researched and is associated with adverse outcomes in heart failure. However, to our knowledge, the temporal evolution of iron status has not been previously investigated in patients with acute coronary syndrome (ACS). Therefore, we aimed to explore the temporal pattern of repeatedly measured iron, ferritin, transferrin, and transferrin saturation (TSAT) in relation to prognosis post-ACS. BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective, multicenter, observational cohort study conducted in The Netherlands between 2008 and 2015. A total of 844 patients with post-ACS were enrolled and underwent high-frequency (median 17) blood sampling during 1 year follow-up. Biomarkers of iron status were measured batchwise in a central laboratory. We analyzed 3 patient subsets, including the case-cohort (n = 187). The primary endpoint (PE) was a composite of cardiovascular mortality and repeat nonfatal ACS, including unstable angina pectoris requiring revascularization. The association between iron status and the PE was analyzed using multivariable joint models. Mean age was 63 years; 78% were men, and >50% had iron deficiency at first sample in the case-cohort. After adjustment for a broad range of clinical variables, 1 SD decrease in log-iron was associated with a 2.2-fold greater risk of the PE (hazard ratio 2.19, 95% confidence interval 1.34 to 3.54, p = 0.002). Similarly, 1 SD decrease in log-TSAT was associated with a 78% increased risk of the PE (hazard ratio 1.78, 95% confidence interval 1.17 to 2.65, p = 0.006). Ferritin and transferrin were not associated with the PE. Repeated measurements of iron and TSAT predict risk of adverse outcomes in patients with post-ACS during 1 year follow-up. Trial Registration: The Netherlands Trial Register. Unique identifiers: NTR1698 and NTR1106. Registered at https://www.trialregister.nl/trial/1614 and https://www.trialregister.nl/trial/1073.

Aims Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients. Methods and results BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02–2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28–2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract). Conclusion Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS. Clinical Trial Registration The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Background. The Nuss procedure is the gold standard surgical treatment for pectus excavatum in young patients. Its use in adults has also been described, although it may be associated with increased postoperative morbidity resulting from higher chest wall rigidity. This study aimed to examine the risk of complications after the Nuss procedure in adult patients compared with young patients with pectus excavatum.Methods. This single-center retrospective cohort study evaluated all patients who underwent the Nuss procedure between 2006 and 2018. Patients were stratified by age as young (24 years old). The primary end point was the occurrence of perioperative or postoperative complications, subdivided into major (Clavien-Dindo class Ill a or higher) and minor (less severe than Clavien-Dindo class III). Between-group differences were analyzed using the Mann-Whitney U and the chi(2) test with post hoc analysis.Results. A total of 327 participants were included, 272 in the young group (median age, 16 years; interquartile range [IQR], 15 to 18 years; range, 11 to 24 years) and 55 in the adult group (median age, 32 years; IQR, 27 to 38 years; range, 25 to 47 years). The median Haller index was similar between groups (young, 3.7; IQR, 3.2 to 4.4 vs adult,3.6; IQR, 3.0 to 4.3; P = .44). The median follow-up was 34 and 36 months, respectively. The incidence of major complications was comparable between young and adult participants (P = .43). Minor complications occurred more often among adults (young, 4% vs adult, 11%; P = .002). Chronic postoperative pain was the only minor complication with a significant difference in incidence (young, 1% vs adult, 7%; P = .008).Conclusions. The Nuss procedure is a safe surgical treatment for pectus excavatum in both young and adult patients. The risk of major complications is comparable. However, adults more often have chronic pain. (C) 2021 by The Society of Thoracic Surgeons

Objectives Details of the biological variability of high-sensitivity C-reactive protein (hs-CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and ST2 are currently lacking in patients with acute coronary syndrome (ACS) but are crucial knowledge when aiming to use these biomarkers for personalized risk prediction. In the current study, we report post-ACS kinetics and the variability of the hs-CRP, NT-proBNP and ST2. Methods BIOMArCS is a prospective, observational study with high frequency blood sampling during 1 year post-ACS. Using 1507 blood samples from 191 patients that remained free from adverse cardiac events, we investigated post-ACS kinetics of hs-CRP, NT-proBNP and ST2. Biological variability was studied using the samples collected between 6 and 12 months after the index ACS, when patients were considered to have stable coronary artery disease. Results On average, hs-CRP rose peaked at day 2 and rose well above the reference value. ST2 peaked immediately after the ACS but never rose above the reference value. NT-proBNP level rose on average during the first 2 days post-ACS and slowly declined afterwards. The within-subject variation and relative change value (RCV) of ST2 were relatively small (13.8%, RCV 39.7%), while hs-CRP (41.9%, lognormal RCV 206.1/-67.3%) and NT-proBNP (39.0%, lognormal RCV 185.2/-64.9%) showed a considerable variation. Conclusions Variability of hs-CRP and NT-proBNP within asymptomatic and clinically stable post-ACS patients is considerable. In contrast, within-patient variability of ST2 is low. Given the low within-subject variation, ST2 might be the most useful biomarker for personalizing risk prediction in stable post-ACS patients.

ObjectiveThe Rate Control versus Electrical Cardioversion Trial 7–Acute Cardioversion versus Wait and See trial compared early to delayed cardioversion for patients with recent-onset symptomatic atrial fibrillation (AF). This study aims to evaluate the adherence to a 4-week mobile health (mHealth) prescription to detect AF recurrences after an emergency department visit.MethodsAfter the emergency department visit, the 437 included patients, irrespective of randomisation arm (early or delayed cardioversion), were asked to record heart rate and rhythm for 1 min three times daily and in case of symptoms by an electrocardiography-based handheld device for 4 weeks (if available). Adherence was appraised as number of performed measurements per number of recordings asked from the patient and was evaluated for longitudinal adherence consistency. All patients who used the handheld device were included in this subanalysis.Results335 patients (58% males; median age 67 (IQR 11) years) were included. The median overall adherence of all patients was 83.3% (IQR 29.9%). The median number of monitoring days was 27 out of 27 (IQR 5), whereas the median number of full monitoring days was 16 out of 27 (IQR 14). Higher age and a previous paroxysm of AF were identified as multivariable adjusted factors associated with adherence.ConclusionsIn this randomised trial, a 4-week mHealth prescription to monitor for AF recurrences after an emergency department visit for recent-onset AF was feasible with 85.7% of patients consistently using the device with at least one measurement per day. Older patients were more adherent.Trial registration numberNCT02248753.

Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited.In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke.A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31).In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.).

Background Life-threatening arrhythmias have been reported in patients with severe pectus excavatum in absence of other cardiac abnormalities. Literature is scarce regarding diagnosis, cause and management of this problem, particularly regarding the question as to whether the placement of an implantable cardioverter-defibrillator (ICD) is necessary. Case summary A 19-year-old male patient with severe pectus excavatum was scheduled for elective surgical correction. During forward bending for epidural catheter placement, syncope and ventricular fibrillation (VF) occurred resulting in cardiac arrest. After successful cardiopulmonary resuscitation, extensive analysis was performed and showed no cause for VF other than cardiac compression (particularly of the left atrium, right atrium, and ventricle to a lesser degree) due to severe pectus excavatum. Postponed correction by modified Ravitch was performed without ICD placement, with an uneventful post-operative recovery. Eighteen months after surgery, the patient remains well. Upon specific request, he did remember dizzy spells when tying shoelaces. He always considered this unremarkable. Discussion In severe pectus excavatum with cardiac compression, forward bending can decrease central venous return and cardiac output, causing hypotension, arrhythmia, and cardiac arrest. In absence of structural or electric abnormalities, cardiac compression by severe pectus excavatum was considered a reversible cause of VF and ICD placement unnecessary. Patients with cardiac compression due to severe pectus excavatum may report pre-existing postural symptoms upon specific request. When these postural symptoms are present, extreme and prolonged forward bending postures should be avoided.

Purpose: The aim of this study was to study temporal changes in metabolite profiles in patients with post-acute coronary syndrome (ACS), in particular prior to the development of recurrent ACS (reACS). Methods: BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective study including patients admitted for ACS, who underwent high-frequency blood sampling during 1-year follow-up. Within BIOMArCS, we performed a nested case-cohort analysis of 158 patients (28 cases of reACS). We determined 151 metabolites by nuclear magnetic resonance in seven (median) blood samples per patient. Temporal evolution of the metabolites and their relation with reACS was assessed by joint modelling. Results are reported as adjusted (for clinical factors) hazard ratios (aHRs). Results: Median age was 64 (25th–75th percentiles; 56–72) years and 78% were men. After multiple testing correction (p < 0.001), high concentrations of extremely large very low density lipoprotein (VLDL) particles (aHR 1.60/SD increase; 95%CI 1.25–2.08), very large VLDL particles (aHR 1.60/SD increase; 95%CI 1.25–2.08) and large VLDL particles (aHR 1.56/SD increase; 95%CI 1.22–2.05) were significantly associated with reACS. Moreover, these longitudinal particle concentrations showed a steady increase over time prior to reACS. Among the other metabolites, no significant associations were observed. Conclusion: Post-ACS patients with persistent high concentrations of extremely large, very large and large VLDL particles have increased risk of reACS within 1 year.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) has multiple potential underlying causes which can be subdivided into coronary, myocardial and non-cardiac disorders. On the basis of three case descriptions, we show that additional investigations are crucial in determining the underlying mechanism and starting suitable treatment. Depending on clinical presentation, risk factors and medical history, an LV angiogram, a provocation test with intracoronary acetylcholine and a cardiac MRI can contribute to finding the correct diagnosis. We further present a diagnostic algorithm to guide the clinician in the management of patients presenting with MINOCA.

The Biomarker Study to Identify the Acute Risk of a Coronary Syndrome (BIOMArCS) is a prospective, observational study that has been designed to study the evolution of blood biomarkers in post-acute coronary syndrome (ACS) patients. In our recently published study "Temporal evolution of Myeloperoxidase and Galectin 3 during 1 year after acute coronary syndrome admission" [1] in the American Heart Journal, we demonstrated that repeatedly measuring MPO and Galectin-3 does not aid to differentiate between patients with and without adverse cardiac events during 1-year follow-up.In this Data-In-Brief article, we present further details on data collections and data analysis. In addition, a detailed description of baseline characteristics and the distribution of blood sampling moments is provided. The BIOMArCS dataset contains clinical information and follow-up data on all enrolled 844 patients. These patients underwent a median of 17 (25th -75th percentile 12-20) repeated blood samples in the first year after the index ACS. Blood samples were stored at -80 degrees C within a median of 82 (25th-75th percentile 58-117) minutes after withdrawal. We collected whole blood, citrate plasma, EDTA plasma, serum and DNA.The dataset used for the analysis in the accompanying research paper has been made available online. We welcome collaborations for further use of our data, whether or not in combination with other biobanks. (C) 2019 The Author(s). Published by Elsevier Inc.

Prior studies reported that Myeloperoxidase and Galectin-3, which are biomarkers of coronary plaque vulnerability, are elevated in acute coronary syndrome (ACS) patients. We studied the temporal evolution of these biomarkers early after ACS admission and prior to a recurrent ACS event during 1 year follow-up.

BACKGROUND: Patients with recent-onset atrial fibrillation commonly undergo immediate restoration of sinus rhythm by pharmacologic or electrical cardioversion. However, whether immediate restoration of sinus rhythm is necessary is not known, since atrial fibrillation often terminates spontaneously.METHODS: In a multicenter, randomized, open-label, noninferiority trial, we randomly assigned patients with hemodynamically stable, recent-onset (RESULTS: The presence of sinus rhythm at 4 weeks occurred in 193 of 212 patients (91%) in the delayed-cardioversion group and in 202 of 215 (94%) in the early-cardioversion group (between-group difference, -2.9 percentage points; 95% confidence interval [CI], -8.2 to 2.2; P = 0.005 for noninferiority). In the delayed-cardioversion group, conversion to sinus rhythm within 48 hours occurred spontaneously in 150 of 218 patients (69%) and after delayed cardioversion in 61 patients (28%). In the early-cardioversion group, conversion to sinus rhythm occurred spontaneously before the initiation of cardioversion in 36 of 219 patients (16%) and after cardioversion in 171 patients (78%). Among the patients who completed remote monitoring during 4 weeks of follow-up, a recurrence of atrial fibrillation occurred in 49 of 164 patients (30%) in the delayed-cardioversion group and in 50 of 171 (29%) in the early-cardioversion group. Within 4 weeks after randomization, cardiovascular complications occurred in 10 patients and 8 patients, respectively.CONCLUSIONS: In patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation, a wait-and-see approach was noninferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks. (Funded by the Netherlands Organization for Health Research and Development and others; RACE 7 ACWAS ClinicalTrials.gov number, NCT02248753.).

BACKGROUND: Current standard of care for patients with recent-onset atrial fibrillation (AF) in the emergency department aims at urgent restoration of sinus rhythm, although paroxysmal AF is a condition that resolves spontaneously within 24 hours in more than 70% of the cases. A wait-and-see approach with rate-control medication only and when needed cardioversion within 48 hours of onset of symptoms is hypothesized to be noninferior, safe, and cost-effective as compared with current standard of care and to lead to a higher quality of life.DESIGN: The ACWAS trial (NCT02248753) is an investigator-initiated, randomized, controlled, 2-arm noninferiority trial that compares a wait-and-see approach to the standard of care. Consenting adults with recent-onset symptomatic AF in the emergency department without urgent need for cardioversion are eligible for participation. A total of 437 patients will be randomized to either standard care (pharmacologic or electrical cardioversion) or the wait-and-see approach, consisting of symptom reduction through rate control medication until spontaneous conversion is achieved, with the possibility of cardioversion within 48 hours after onset of symptoms. Primary end point is the presence of sinus rhythm on 12-lead electrocardiogram at 4 weeks; main secondary outcomes are adverse events, total medical and societal costs, quality of life, and cost-effectiveness for 1 year.CONCLUSIONS: The ACWAS trial aims at providing evidence for the use of a wait-and-see approach for patients with recent-onset symptomatic AF in the emergency department.

PURPOSE: Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such 'vulnerable periods'. PARTICIPANTS: BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor. METHODS AND ANALYSIS: We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate 'vulnerable periods' during which patients with CAD are at high short-term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for non-fatal ACS had occurred in 50 patients. A case-cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS. FUTURE PLANS AND DISSEMINATION: Follow-up and event adjudication have been completed. Prespecified biomarker analyses are currently being performed and dissemination through peer-reviewed publications and conference presentations is expected from the third quarter of 2016. Should identification of a 'vulnerable period' prove to be feasible, then future research could focus on event reduction through pharmacological or mechanical intervention during such periods of high risk for ACS. TRIAL REGISTRATION NUMBER: NTR1698 and NTR1106.

Objective To evaluate the predictive value of seven biomarkers, which individually have been shown to be independent predictors, for use in a combined multimarker model for long-term cardiovascular outcome after non-ST-segment elevation acute coronary syndrome (NSTEACS). Design and Setting Levels of high-sensitivity C-reactive protein (hsCRP), myeloperoxidase, pregnancy-associated plasma protein A, placental growth factor (PlGF), soluble CD40 ligand (sCD40L), interleukin 10 (IL-10) and troponin-T (TnT) were determined in patients enrolled in the CAPTURE trial. Cox proportional hazard regression analyses were applied to evaluate the relation between biomarkers and the occurrence of all-cause mortality or non-fatal myocardial infarction (MI). Patients 1090 patients with NSTEACS. Main outcome measure All-cause mortality and non-fatal MI during a median follow-up of 4 years. Results The composite endpoint was reached by 15.3% of patients. Admission levels of TnT >0.01 mg/l (adjusted HR 1.8), IL-10 350 mg/l (1.5) and PlGF >27 ng/l (1.9) remained significant predictors for the incidence of all-cause mortality or non-fatal MI after multivariable adjustment for other biomarkers and clinical characteristics, whereas hsCRP, pregnancy-associated plasma protein A and sCD40L were only associated with the endpoint in univariate analysis. A multimarker model consisting of TnT, IL-10, myeloperoxidase and PlGF predicted 4-year event rates that varied between 6.0% (all markers normal) and 35.8% (three or more biomarkers abnormal). Conclusion In patients with NSTEACS, biomarkers characterising distinct aspects of the underlying atherosclerotic process and myocardial damage of the initial cardiac event can assist in predicting long-term adverse cardiac outcomes. The use of combinations of selected biomarkers adds incremental predictive value to further risk stratification in an otherwise seemingly homogeneous NSTEACS population.

The incidence and prevalence of dyspnea increases with age. Frequently, for the general practitioner with his limited diagnostic facilities, it is impossible to separate dyspnea from cardiac causes and non-cardiac causes. Without cardiac imaging it is also impossible to separate systolic dysfunction from diastolic dysfunction. After a thorough physical examination, initial screening of systolic and diastolic heart failure can be done by measurement of plasma NT-pro BNP or plasma BNP. Additionally a Chest X-Ray or ECG can be performed. To improve diagnostic performance an open access echocardiographic service can be initiated. Recent studies showed, that open access echocardiography can easily detect systolic and diastolic dysfunction in the community and can separate cardiac from non-cardiac dyspnea.

Acute myocardial infarction during pregnancy is a rare clinical condition. We present a case of a 36-year old woman in her 36th week of pregnancy with an acute anterior ST-elevated myocardial infarction (STEMI) caused by an occlusive proximal LAD. First treatment was thrombosuction, followed by placement of a bioresolvable vascular scaffold. Because of post procedural fetal bradycardia an emergency cesarean section was performed on the same day, despite all antithrombotic medications.

Objectives This study sought to evaluate the predictive value of baseline placental growth factor (PlGF) for long-term cardiovascular events in acute coronary syndromes (ACS). Background A biomarker of vascular inflammation, PlGF is identified as a powerful predictor for short-term outcome in patients with ACS. Methods In 544 patients who were enrolled in the placebo arm of the c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina (CAPTURE) trial, PlGF levels were determined as well as markers of myocardial necrosis (troponin T [TnT]), general inflammation (high-sensitivity C-reactive protein [hsCRP]), and platelet activation (soluble CD40 ligand [sCD40L]). Cox proportional hazard regression analyses were applied to evaluate the relationship between biomarkers and the occurrence of all-cause death or non-fatal myocardial infarction during a median follow-up period of four years. Results Patients with PlGF levels in the fourth and fifth quintile (>27 ng/l) had higher mortality than those with lower levels (10.8% vs. 3.2%; hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6 to 7.1), as well as a higher incidence of the composite end point of death or myocardial infarction (27.6% vs. 11.3% events; HR, 2.6; 95% CI, 1.7 to 3.9). The relationship between PlGF and the composite end point remained significant after adjustment for TnT, sCD40L, and hsCRP (adjusted HR, 3.3; 95% CI, 2.0 to 5.4). Conclusions In patients with ACS, elevated plasma levels of PlGF are associated with adverse cardiac outcomes during long-term follow-up. These data suggest that PlGF as a more specific marker of vascular inflammation should be considered for risk stratification of patients with ACS rather than general markers of inflammation.

The glycoprotein IIb/IIIa receptor antagonist abciximab reduces the risk of thrombotic complications with percutaneous coronary intervention, but also has been associated with higher bleeding rates.In the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO IV-ACS) trial, abciximab (either a 24-hour or 48-hour infusion) was compared with placebo in 7800 patients with an acute coronary syndrome. During study drug administration, 2% of the patients underwent a revascularization procedure.In 1507 patients (19.3%), bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) classification was observed while they were hospitalized or within 7 days. Ninety-eight patients (1.2%) had a major bleed, including 8 with intracranial hemorrhages. In 215 patients (2.8%), a minor bleed was reported, and in 1194 patients (15.3%), an insignificant bleed was reported. Bleeding was more frequent in patients receiving a 48-hour infusion of abciximab. Spontaneous bleeding was seen in 911 patients (11.7%). The other 596 patients had a bleeding event in conjunction with a procedure. The most significant predictors for bleeding with multivariable analysis were: use of low-molecular weight heparin, duration of abciximab infusion, region of hospitalization, performance of coronary artery bypass grafting or percutaneous coronary intervention (PCI), advanced age, and female sex. For major bleeding, the predictors were performance of coronary artery bypass grafting or PCI, long duration of abciximab administration, and advanced age.Treatment with abciximab in patients with non-ST-elevation acute coronary syndromes is safe because major bleeding and stroke are rare, and most events are clinically manageable or have few clinical consequences. Guidelines for use of abciximab in combination with other antithrombotic agents developed for PCI should also be respected in acute coronary syndromes. Specific dosing guidelines for combination with low-molecular weight heparin must be developed for patients who subsequently will undergo a PCI.

Background The aim of this study was to evaluate whether in patients with myocardial infarction, the intensity and duration of myocardial ischemia as measured by continuous ST monitoring are associated with infarct size and residual left ventricular function. Methods and Results The analyses included patients with myocardial infarction, receiving thrombolytic therapy, who were enrolled in the electrocardiographic substudy of GUSTO-I, monitored by a vector-derived 12-lead electrocardiographic recording system, and in whom either infarct size (defined as cumulative release of α-hydroxybutyrate dehydrogenase activity per liter of plasma over a 72-hour period [Q(72)]) or left ventricular ejection fraction (LVEF) was determined. With the use of linear regression analysis, we investigated the association of various ST-trend characteristics with Q(72) (206 patients) and with LVEF (180 patients). A higher area under the ST trend since thrombolysis until 50% ST recovery and a higher area under recurrent ischemic episodes (ST reelevations) were significantly associated with a higher Q(72), whereas only a higher area under recurrent ischemic episodes was significantly associated with a lower LVEF. These associations remained after adjusting for other patient characteristics such as age, sex, infarct location, and time to treatment. Conclusions These findings support the physiologic hypothesis that both the intensity and duration of myocardial ischemia (both reflected by the estimated areas under the ST-trend curve) determine myocardial damage and thus are associated with infarct size and ejection fraction in patients with acute myocardial infarction who receive thrombolytic therapy. (Am Heart J 1999;138:525-32.)

The selection of ECG leads used for ST monitoring may influence detection and quantitation of ischaemia.We compared on-line continuous 48-h 12-lead against 3-lead ST monitoring in 130 unstable angina patients (Mortara. ELI-100). Onset and offset of ST episodes were defined by the lead with the firstor = 100 microV ST change relative to baseline and the lead with the latest return to baseline ST level, respectively. ST episodes were calculated for 12 leads and 3 leads (V2, V5, III) separately.ST episodes were detected in 88 patients (77%) by 12-lead and in 71 patients (62%) by 3-lead ST monitoring (P0.02). The median number (25.75%) of episodes/patient was 1 (0.3) for 3-lead and 2 (1.6) for 12-lead (P0.0001). The total duration of ischaemia detected during 12-lead far exceeded 3-lead monitoring: 12.3 (1, 58.2) and 1.7 (0, 23.3) min respectively (P0.0001). The probability of recurrent ischaemia declined most during the first 24 h of monitoring. After a period without ST changes of 1, 12, 24 and 36 h, the probabilities of recurrent ischaemia were 63, 31, 14 and 9%, respectively.Continuous 12-lead ST monitoring increases detection rate and duration of ST episodes compared to 3-lead ST monitoring. The use of continuous 12-lead ECG monitoring devices on emergency wards and coronary care units is recommended.

BACKGROUND: The recent international GUSTO trial of 41,021 patients with acute myocardial infarction demonstrated improved 90-min infarct related artery patency as well as reduced mortality in patients treated with an accelerated regimen of tissue plasminogen activator, compared to patients treated with streptokinase. A regimen combining tissue plasminogen activator and streptokinase yielded intermediate results. The present study investigated the effects of treatment on infarct size and enzyme release kinetics in a subgroup of these patients. METHODS: A total of 553 patients from 15 hospitals were enrolled in the study. Four thrombolytic strategies were compared: streptokinase with subcutaneous heparin, streptokinase with intravenous (i.v.) heparin, tissue plasminogen activator with i.v. heparin, and streptokinase plus tissue plasminogen activator with i.v. heparin. The activity of alpha-hydroxybutyrate dehydrogenase (HBDH) in plasma was centrally analysed and infarct size was defined as cumulative HBDH release per litre of plasma within 72 h of the first symptoms (Q(72)). Patency of the infarct-related vessel was determined by angiography in 159 patients, 90 min after treatment. RESULTS: Infarct size was 3.72 g-eq.1(-1) in patients with adequate coronary perfusion (TIMI-3) at the 90 min angiogram and larger in patients with TIMI-2 (4.35 g-eq.1(-1) or TIMI 0-1 (5.07 g-eq.1(-1) flow (P = 0.024). In this subset of the GUSTO angiographic study, early coronary patency rates (TIMI 2 + 3) were similar in the two streptokinase groups (53 and 46%). Higher, but similar, patency rates were observed in the tissue plasminogen activator and combination therapy groups (87 and 90%). Median infarct size for the four treatment groups, expressed in gram-equivalents (g-eq) of myocardium, was 4.4, 4.5, 3.9 and 3.9 g-eq per litre of plasma (P = 0.04 for streptokinase vs tissue plasminogen activator). Six hours after the first symptoms, respectively 5.3, 6.6, 14.0 and 13.6% of total HBDH release was complete (P < 0.0001 for streptokinase vs tissue plasminogen activator). CONCLUSIONS: Rapid and complete coronary reperfusion salvages myocardial tissue, resulting in limitation of infarct size and accelerated release of proteins from the myocardium. Treatment with tissue plasminogen activator, resulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differences in survival between treatment groups in the GUSTO trial.

Objective To assess the practical application, safety and long-term outcome of pre-hospital thrombolytic intervention with either alteplase or streptokinase in patients with extensive myocardial infarction. Design Prospective study. Subjects Patients with chest pain of more than 30 min duration, presenting within 6 h of symptom onset and with electrocardiographic evidence of extensive evolving myocardial infarction. Methods Eligibility of patients was established by the general practitioner or the ambulance nurse using a standardized questionnaire with (contra-) indications for thrombolytic therapy. Computerized ECG was recorded by ambulance nurses. In the presence of extensive ST segment elevation (sum ST deviation of at least 1.0 m V), eligible patients received either 100 mg alteplase (n=246) or 50 mg alteplase in the ambulance followed by 0.75 × 106 IE streptokinase in hospital (n=90), or 1.5 × 106 IE streptokinase intravenously (n=193). Main outcome measurements Death and life-threatening complications (ventricular fibrillation, cardiac arrest) and side effects (hypotension, allergic reactions) during transportation to hospital and in the first 24 h following hospitalization, and survival up to 5 years follow-up. Results From 1988–1993, 529 patients received thrombolytic treatment initiated pre-hospital. The time gained by pre-hospital administration of thrombolysis amounted to 50 min. The rate of complications during transportation and during the first 24 h after hospitalization was low. Hospital mortality was 2% and 1-year mortality 3%. Cumulative survival at 5 years was 92%. This was superior to the 84% 5-year survival observed in a matched group of 239 patients with similar baseline characteristics treated with alteplase in hospital. Conclusions Pre-hospital administration of either alteplase or streptokinase is feasible and safe and results in significant time gain. The long-term prognosis is excellent in spite of extensive evolving myocardial infarction upon admission.

Background Long-term follow-up in patients treated with thrombolysis for acute myocardial infarction thus far has been reported in a few studies only, and no long-term follow-up is available for patients who underwent additional percutaneous transluminal coronary angioplasty (PTCA). This report describes 5-year survival as collected in patients who received placebo, recombinant tissue plasminogen activator (rTPA), or rTPA with additional immediate PTCA in two European Cooperative Study Group trials. Determinants for long-term survival were assessed in 1043 patients discharged alive. Methods and Results Five-year follow-up information on mortality was collected. Hospital mortality was lower after rTPA than placebo (2.5% versus 5.7%, P =.04) and higher after rTPA with immediate PTCA compared with rTPA without additional intervention (6.0% versus 2.2%, P =.07). Of the 1043 hospital survivors, data were available for 923 patients, of whom 109 died. In the placebo group, mortality after hospital discharge was 10.7% versus 11.0% in the comparative rTPA group. The patients treated with rTPA and immediate PTCA had a mortality rate of 10.5% versus 8.9% in the rTPA group without PTCA (all P =NS). Significant determinants of mortality in multivariate proportional hazards analysis were enzymatic infarct size, indicators of residual left ventricular function, number of diseased vessels and TIMI perfusion grade at discharge. Patients with TIMI grade 2 flow had mortality rates similar to those with TIMI flow grades 0 and 1, while prognosis was better in patients with TIMI flow grade 3. Conclusions The initial in-hospital benefit of thrombolysis with intravenous rTPA is maintained throughout 5 years, with no early or late beneficial effect of systematic immediate PTCA. Enzymatic infarct size, left ventricular function, and extent of coronary artery disease are predictors for long-term survival. TIMI perfusion grade 2 at discharge should be considered as an inadequate result of therapy.

Statins provide effective secondary prevention in cardiovascular disease. However, it remains uncertain how soon statins should be started after an acute coronary syndrome (ACS). Recently published trials suggest starting before discharge. We hypothesize that statins should be initiated without delay.Data from a large cohort of 10,484 consecutive patients with an ACS were analysed. Of this cohort, 1426 first-time statin receivers and survivors of the first 24 h were compared with 6771 first-day survivors not receiving statin therapy. A propensity score for the likelihood of receiving statin therapy within 24 h was developed and used with other established risk factors in a multivariable analysis. There was a significantly reduced all-cause 7-day mortality in patients receiving early statin therapy [0.4 vs. 2.6%, unadjusted hazard ratio (HR) 0.16, 95% confidence interval (CI) 0.08-0.37, adjusted HR 0.34, 95% CI 0.15-0.79]. Statistical significance was observed in patients presenting with STE-ACS (adjusted HR 0.17, 95% CI 0.04-0.70) and not in NSTE-ACS patients. However, no statistical evidence of heterogeneity in treatment effect was observed between these groups.These data suggest that very early statin therapy is associated with reduced mortality in patients presenting with STE-ACS; however, these findings have to be confirmed by prospective, randomized controlled trials before firm treatment recommendations can be given.

Aims Treatment with the glycoprotein IIb/IIIa receptor antagonist abciximab before and during coronary intervention in refractory unstable angina improves early outcome. We collected 4-year follow-up data to assess whether this benefit is sustained. Additionally, we investigated the predictive value of baseline troponin T and CRP for long-term cardiovascular events. Methods and Results Of 1265 patients enrolled in the CAPTURE trial follow-up was available in 94% of the patients alive after 6 months (median 48 months). Survival was similar in both groups. Both elevated troponin T and CRP were associated with impaired outcome, independently of other established risk factors, but with a different time course. Elevated troponin was associated with increased procedure related risk, and elevated CRP with increased risk for subsequent events. Lower rates of the composite end-point of death or myocardial infarction with abciximab vs. placebo were sustained during long-term follow up: 15.7% vs 17.2% at 4 years (P = ns), particularly in patients with elevated troponin T: 16.9% with abciximab vs 28.4% with placebo: P = 0.015. Elevated CRP was not associated with specific benefit of abciximab. Conclusion Troponin T as a marker of thrombosis and CRP as a marker of inflammation are independent predictors of impaired outcome at 4 years follow-up. The initial benefit from abciximab with regard to death and myocardial infarction was preserved at 4 years. No specific benefit with abciximab was observed for patients with elevated CRP, suggesting that a chronic inflammatory process is not affected by abciximab. In contrast the benefit of treatment in patients with elevated troponin T implies that the acute thrombotic process in refractory unstable angina is treated effectively.

The Cordis tantalum coil stent was assessed in a nonrandomized multicenter trial: 275 patients with stable or unstable angina were entered. Clinical follow-up was for 1 year, with repeat angiography at 6 months. The major adverse cardiac event rates (MACE) were 3%, 14%, and 17% at 1, 7, and 13 months, respectively. The procedural success rate was 96% and the subacute occlusion rate 1.5%, in a group of patients over 60% of whom had ACC/AHA type B2 or C lesions. The binary restenosis rate at 6 months was 17.3%. Minimum lumen diameter increased from 1.07 +/- 0.28 mm preprocedure to 2.93 +/- 0.34 mm poststenting and at 6 months was 1.99 +/- 0.69 mm. These results demonstrate that the Cordis tantalum stent can be used to treat complex lesions with good procedural success and low rates of subacute thrombosis and restenosis at 6 months.

Aims Thrombin plays a key role in the clinical syndrome of unstable angina. We investigated the safety and eYcacy of five dose levels of efegatran sulphate, a direct thrombin inhibitor, compared to heparin in patients with unstable angina. Methods Four hundred and thirty-two patients with unstable angina were enrolled. Five dose levels of efegatran were studied sequentially, ranging from 0·105 mg . kg "1 .h "1 to 1·2 mg . kg "1 .h "1 over 48 h. Safety was assessed clinically, with reference to bleeding and by measuring clinical laboratory parameters. EYcacy was assessed by the number of patients experiencing any episode of recurrent ischaemia as measured by computer-assisted continuous ECG ischaemia monitoring. Clinical end-points were: episodes of recurrent angina, myocardial infarction, coronary intervention (PTCA or CABG), and death. Results Efegatran demonstrated dose dependent ex-vivo anticoagulant activity with the highest dose level of 1·2 mg . kg "1 .h "1 resulting in steady state mean activated partial thromboplastin time values of approximately three times baseline. Thrombin time was also increased. Neither of the efegatran doses studied were able to suppress myocardial ischaemia during continuous ECG ischaemia monitoring to a greater extent than that seen with heparin. There were no statistically significant diVerences in clinical outcome or major bleeding between the efegatran and heparin groups. Minor bleeding and thrombophlebitis occurred more frequently in the efegatran treated patients. Conclusion Administration of efegatran sulphate at levels of at least 0·63 mg . kg "1 .h "1 provided an antithrombotic eVect which is at least comparable to an activated partial thromboplastin time adjusted heparin infusion. There was no excess of major bleeding. The level of thrombin inhibition by efegatran, as measured by activated partial thromboplastin time, appeared to be more stable than with heparin. Thus, like other thrombin inhibitors, efegatran sulphate is easier to administer than heparin. However, no clinical benefits of efegatran over heparin were apparent. (Eur Heart J 1999; 20: 1101‐1111)

Background —In the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina) trial, 1265 patients with refractory unstable angina were treated with abciximab or placebo, in addition to standard treatment from 16 to 24 hours preceding coronary intervention through 1 hour after intervention. To investigate the incidence of recurrent ischemia and the ischemic burden, a subset of 332 patients (26%) underwent continuous vector-derived 12-lead ECG-ischemia monitoring. Methods and Results —Patients were monitored from start of treatment through 6 hours after coronary intervention. Ischemic episodes were detected in 31 (18%) of the 169 abciximab and in 37 (23%) of the 163 placebo patients (NS). Only 9 (5%) of abciximab versus 22 (14%) of placebo patients had ≥2 ST episodes ( P P Conclusions —Recurrent ischemia predicts MI or death within 5 days of follow-up. Treatment with abciximab is associated with a reduction of frequent ischemia and a reduction of total ischemic burden in patients with refractory unstable angina. As such, patients with ischemia derive particularly high benefit from abciximab.