Jan Madsen

Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events

AIMS Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus. METHODS AND RESULTS We identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Coxs models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively. CONCLUSION Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.

Proton-Pump Inhibitors Are Associated With Increased Cardiovascular Risk Independent of Clopidogrel Use: A Nationwide Cohort Study

BACKGROUND Controversy remains on whether the dual use of clopidogrel and proton-pump inhibitors (PPIs) affects clinical efficacy of clopidogrel. OBJECTIVE To examine the risk for adverse cardiovascular outcomes related to concomitant use of PPIs and clopidogrel compared with that of PPIs alone in adults hospitalized for myocardial infarction. DESIGN A nationwide cohort study based on linked administrative registry data. SETTING All hospitals in Denmark. PATIENTS All patients discharged after first-time myocardial infarction from 2000 to 2006. MEASUREMENTS The primary outcome was a composite of rehospitalization for myocardial infarction or stroke or cardiovascular death. Patients were examined at several assembly time points, including 7, 14, 21, and 30 days after myocardial infarction. Follow-up was 1 year. RESULTS Of 56 406 included patients, 9137 (16.2%) were re-hospitalized for myocardial infarction or stroke or experienced cardiovascular death. Of the 24 702 patients (43.8%) who received clopidogrel, 6753 (27.3%) received concomitant PPIs. The hazard ratio for cardiovascular death or rehospitalization for myocardial infarction or stroke for concomitant use of a PPI and clopidogrel among the cohort assembled at day 30 after discharge was 1.29 (95% CI, 1.17 to 1.42). The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29 (CI, 1.21 to 1.37). No statistically significant interaction occurred between a PPI and clopidogrel (P = 0.72). LIMITATIONS Unmeasured and residual confounding, time-varying measurement errors of exposure, and biases from survival effects were possible. CONCLUSION Proton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction. Dual PPI and clopidogrel use was not associated with any additional risk for adverse cardiovascular events over that observed for patients prescribed a PPI alone.

Comparison of Paclitaxel- and Sirolimus-Eluting Stents in Everyday Clinical Practice: The SORT OUT II Randomized Trial

CONTEXT Approval of drug-eluting coronary stents was based on results of relatively small trials of selected patients; however, in routine practice, stents are used in a broader spectrum of patients. OBJECTIVE To compare the first 2 commercially available drug-eluting stents-sirolimus-eluting and paclitaxel-eluting-for prevention of symptom-driven clinical end points, using a study design reflecting everyday clinical practice. DESIGN, SETTING, AND PATIENTS Randomized, blinded trial conducted August 2004 to January 2006 at 5 university hospitals in Denmark. Patients were 2098 men and women (mean [SD] age, 63.6 [10.8] years) treated with percutaneous coronary intervention (PCI) and randomized to receive either sirolimus-eluting (n = 1065) or paclitaxel-eluting (n = 1033) stents. Indications for PCI included ST-segment elevation myocardial infarction (STEMI), non-STEMI or unstable angina pectoris, and stable angina. MAIN OUTCOME MEASURES The primary end point was a composite clinical end point of major adverse cardiac events, defined as either cardiac death, acute myocardial infarction, target lesion revascularization, or target vessel revascularization. Secondary end points included individual components of the composite end point, all-cause mortality, and stent thrombosis. RESULTS The sirolimus- and the paclitaxel-eluting stent groups did not differ significantly in major adverse cardiac events (98 [9.3%] vs 114 [11.2%]; hazard ratio, 0.83 [95% confidence interval, 0.63-1.08]; P = .16) or in any of the secondary end points. The stent thrombosis rates were 27 (2.5%) and 30 (2.9%) (hazard ratio, 0.87 [95% confidence interval, 0.52-1.46]; P = .60), respectively. CONCLUSION In this practical randomized trial, there were no significant differences in clinical outcomes between patients receiving sirolimus- and paclitaxel-eluting stents. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00388934.

LYCOS: the Lyngby Co-Synthesis System

This paper describes the LYCOS system, an experimental co-synthesis environment. We present the motivation and philosophy of LYCOS and after an overview of the entire system, the individual parts are described. We use a single CPU, single ASIC target architecture and we describe the techniques we use to estimate metrics concerning hardware, software and communication in this architecture. Finally we present a novel partitioning technique called PACE, which has shown to produce excellent results, and we demonstrate how partitioning is used to do design space exploration.

Women with acute coronary syndrome are less invasively examined and subsequently less treated than men

AIMS To investigate if gender bias is present in todays setting of an early invasive strategy for patients with acute coronary syndrome in Denmark (population 5 million). METHODS AND RESULTS We identified all patients admitted to Danish hospitals with acute coronary syndrome in 2005-07 (9561 women and 16 406 men). Cox proportional hazard models were used to estimate the gender differences in coronary angiography (CAG) rate and subsequent revascularization rate within 60 days of admission. Significantly less women received CAG (cumulative incidence 64% for women vs. 78% for men, P < 0.05), with a hazard ratio (HR) of 0.68 (95% CI 0.65-0.70, P < 0.0001) compared with men. The difference was narrowed after adjustment for age and comorbidity, but still highly significant (HR 0.82, 95% CI 0.80-0.85, P < 0.0001). Revascularization after CAG was less likely in women with an HR of 0.68 (95% CI 0.66-0.71, P < 0.0001) compared with men. More women (22%) than men (10%) (P < 0.0001) had no significant stenosis on their coronary angiogram. However, after adjustment for the number of significant stenoses, age, and comorbidity women were still less likely to be revascularized (HR 0.91, 95% CI 0.87-0.95, P < 0.0001). CONCLUSION Women with ACS are approached in a much less aggressively invasive way and receive less interventional treatment than men even after adjusting for differences in comorbidity and number of significant stenoses.

Significance and management of early graft failure after coronary artery bypass grafting. Feasibility and results of acute angiography and re-re-vascularization

UNLABELLED Perioperative ischaemia and infarction after CABG are associated with increased morbidity and mortality. OBJECTIVE To study causes of perioperative ischaemia and infarction by acute re-angiography and to treat incomplete re-vascularization caused by graft failure or any other cause. METHODS Between 1990 and 1995, 2003 patients underwent an isolated CABG operation. Myocardial ischaemia was suspected if one or more of the following criteria were present: New changes in the ST-segment in the ECG; a CKMB value greater than 80 U/L; new Q-waves in the ECG; recurrent episodes of, or sustained ventricular tachyarrhythmia; ventricular fibrillation; haemodynamic deterioration and left ventricular failure. Acute coronary angiography was performed in stable patients, while haemodynamically severely compromised patients were rushed to the operating room. RESULTS A total of 71 (3.5%) patients of all CABGs with suspected graft failure were identified and included in the study. Patients were grouped according to whether they had an acute re-angiography (n = 59; group 1) or an immediate re-operation (n = 12; group 2) performed. In group 1, the acute re-angiography demonstrated graft failure/incomplete re-vascularization in 43 patients (73%). The angiographic findings were: Occluded vein graft(s) in 19 (32%); poor distal run-off to the grafted coronary artery in ten (17%); internal mammary artery stenosis in four (7%); internal mammary artery occlusion in three (5%); vein graft stenoses in three (5%); left mammary artery subclavian artery steal in two (3%); and the wrong coronary artery grafted in one (2%). Based on the angiography findings, 27 patients were re-operated and re-grafted. At the time of re-operation, 18 patients (67%) had evolving infarction documented by ECG or CKMB. Two patients (3%) experienced stroke in immediate relation to the re-angiography. The 30-day mortality was three (7%). In group 2, graft occlusions were found in 11 patients (92%). The 30-day mortality was six (50%). CONCLUSION An acute re-angiography demonstrated graft failure or incomplete re-vascularization in the majority of patients with myocardial ischaemia early after CABG. Re-operation for re-re-vascularization was performed with low risk. Few patients with circulatory collapse could be saved by an immediate re-operation without preceding angiography.

PACE: a dynamic programming algorithm for hardware/software partitioning

This paper presents the PACE partitioning algorithm which is used in the LYCOS co-synthesis system for partitioning control/dataflow graphs into hardware and software parts. The algorithm is a dynamic programming algorithm which solves both the problem of minimizing system execution time with a hardware area constraint and the problem of minimizing hardware area with a system execution time constraint. The target architecture consists of a single microprocessor and a single hardware chip (ASIC, FPGA, etc.) which are connected by a communication channel. The algorithm incorporates a realistic communication model and thus attempts to minimize communication overhead. The time-complexity of the algorithm is O(n/sup 2//spl middot//spl Ascr/) and the space-complexity is O(n/spl middot//spl Ascr/) where /spl Ascr/ is the total area of the hardware chip and n the number of code fragments which may be placed in either hardware or software.

Field Triage Reduces Treatment Delay and Improves Long-Term Clinical Outcome in Patients With Acute ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

OBJECTIVES We evaluated the independent impact of field triage on treatment delay and long-term clinical outcome in a large contemporary, consecutive population of ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). BACKGROUND Reduction of treatment delay is crucial for patients with STEMI. METHODS From January 2005 to July 2008, 1,437 STEMI patients were treated with pPCI at a single high-volume invasive center. We present the 1-year outcome in this observational registry study. RESULTS A total of 616 patients were admitted by field triage and 821 by emergency departments. Baseline and angiographic variables were similar in the 2 populations. Patients admitted by field triage had a significantly shorter median door-to-balloon time compared with patients admitted by emergency department triage (83 min, interquartile range 67 to 100 min vs. 103 min, interquartile range 80 to 135 min; p<0.001). Door-to-balloon times of less than the recommended 90 min were achieved in 61% of field triage patients, but only in 36% of nonfield-triage patients (p<0.001). After adjustment for relevant baseline variables, patients admitted by field triage had a reduced risk of reaching the combined end point of all-cause mortality or nonfatal myocardial infarction (hazard ratio: 0.67; 95% confidence interval: 0.46 to 0.97; p=0.035). CONCLUSIONS This study shows that field triage of STEMI patients to pPCI significantly reduces treatment delay and improves outcome. These results emphasize the value of field triage as an important tool in the quest to improve clinical outcomes in STEMI patients undergoing pPCI.

Integrating communication protocol selection with hardware/software codesign

This paper explores the problem of determining the characteristics of the communication links in a computer system as well as determining the best functional partitioning. In particular, we present a communication estimation model and show, by the use of this model, the importance of integrating communication protocol selection with hardware/software partitioning. The communication estimation model allows for fast estimation but is still sufficiently detailed as to allow the designer or design tool to efficiently explore tradeoffs between throughputs, bus widths, burst/nonburst transfers, operating frequencies of system components such as buses, CPUs, ASICs, software code size, hardware area, and component prices. A distinct feature of the model is the modeling of driver processing of data (packing, splitting, compression, etc.) and its impact on communication throughput. The integration of communication protocol selection and communication driver design with hardware/software partitioning is illustrated by a number of design space exploration experiments carried out within the LYCOS cosynthesis system, using models of the PCI and USB protocols.

A Network Traffic Generator Model for Fast Network-on-Chip Simulation

For systems-on-chip (SoC) development, a predominant part of the design time is the simulation time. Performance evaluation and design space exploration of such systems in bit- and cycle-true fashion is becoming prohibitive. We propose a traffic generation (TG) model that provides a fast and effective network-on-chip (NoC) development and debugging environment. By capturing the type and the timestamp of communication events at the boundary of an IP core in a reference environment, the TG can subsequently emulate the cores communication behavior in different environments. Access patterns and resource contention in a system are dependent on the interconnect architecture, and our TG is designed to capture the resulting reactiveness. The regenerated traffic, which represents a realistic workload, can thus be used to undertake faster architectural exploration of interconnection alternatives, effectively decoupling simulation of IP cores and of interconnect fabrics. The results with the TG on an AMBA interconnect show a simulation time speedup above a factor of 2 over a complete system simulation, with close to 100 % accuracy.