Atherosclerotic Plaque Stability Is Affected by the Chemokine CXCL10 in Both Mice and Humans.

Background. The chemokine CXCL10 is specifically upregulated during experimental development of plaque with an unstable phenotype. In this study we evaluated the functional consequences of these findings in mice and humans. Methods and Results. In ApoE(-/-) mice, we induced unstable plaque with using a flow-altering device around the carotid artery. From week 1 to 4, mice were injected with a neutralizing CXCL10 antibody. After 9 weeks, CXCL10 inhibition resulted in a more stable plaque phenotype: collagen increased by 58% (P = 0.002), smooth muscle cell content increased 2-fold (P = 0.03), while macrophage MHC class II expression decreased by 50% (P = 0.005). Also, the size of necrotic cores decreased by 41% (P = 0.01). In 106 human carotid endarterectomy specimens we found that increasing concentrations of CXCL10 strongly associate with an increase in atheromatous plaque phenotype (ANOVA, P = 0.003), with high macrophage, low smooth muscle cell, and low collagen content. Conclusions. In the present study we showed that CXCL10 is associated with the development of vulnerable plaque in human and mice. We conclude that CXCL10 might provide a new lead towards plaque-stabilizing therapy.

Impact of an alerting clinical decision support system for glucose control on protocol compliance and glycemic control in the intensive cardiac care unit.

BACKGROUND: Glycemic control in patients with acute cardiac conditions is a clinical challenge but may substantially improve patient outcome. The aim of the current study was to evaluate the effect of implementing an automated version of an existing insulin protocol for glucose regulation in the Intensive Cardiac Care Unit (ICCU) on compliance with the protocol and achievement of glycemic targets. METHODS: During an 11-month period, data of 667 patients with two or more glucose measurements were evaluated, 425 before and 242 after implementation of the clinical decision support system (CDSS) for glucose control at the Erasmus Medical Center ICCU (Rotterdam, The Netherlands). RESULTS: After implementation, compliance with the advised measurement time increased from 40% to 52% (P < 0.001), and compliance regarding insulin dosage increased from 49% to 61% (P < 0.001). Also, more patients had a mean glucose level within the target range of 81-126 mg/dL (31% vs. 43% [P = 0.01]). Monthly evaluation identified reasons for protocol noncompliance (e.g., nutritional status and time of day) and will be used to improve the existing CDSS. CONCLUSIONS: The CDSS implementation of an insulin protocol in an ICCU improved compliance, identified targets for further improvement of the protocol, and resulted in improved glucose regulation after implementation.

Evaluation of a clinical decision support system for glucose control: impact of protocol modifications on compliance and achievement of glycemic targets.

Treating hyperglycemia may improve patient outcome, but is a clinical challenge. Three variations of a computerized insulin protocol were compared with regard to protocol compliance and achievement of glucose target levels. In group 1, the existing protocol was applied, in group 2 the protocol was modified to account for decreasing glucose values; group 3 had a higher threshold for initiating insulin, wider glucose target ranges, and included instructions to regulate glucose around mealtimes. From July 28, 2008 until February 1, 2010, data from 1255 patients admitted to our Intensive Cardiac Care Unit with at least 2 glucose measurements were analyzed. Mean age was 64 +/- 15 years, 66% were male, 21% had diabetes. Groups 1 to 3 included 269, 814, and 142 patients, respectively. Protocol compliance in group 2 was lower with 44% of the glucose measurements performed on time versus 51% in group 1 (P < 0.001), and insulin was dosed correctly in 57% versus 67% (P < 0.001). In group 3, compliance increased, 52% of the measurements were done on time, and insulin was dosed correctly in 71%. Average glucose levels increased in group 3 due to a higher threshold for starting insulin and a wider target range: 70% (group 1), 66% (group 2), and 61% (group 3) had an average glucose of <8 mmol/L (P < 0.001). Also, we observed a decreasing trend in incidence of hypoglycemia and reporting of noncompliance. Further improvements in glucose measurement technology and protocols are needed to optimally treat hyperglycemia in the Intensive Cardiac Care Unit.

Abnormal spatial QRS-T angle predicts mortality in patients undergoing dobutamine stress echocardiography for suspected coronary artery disease.

OBJECTIVE: To investigate the association between (cardiac) mortality and spatial QRS-T angle in patients undergoing dobutamine - atropine stress echocardiography (DSE) for evaluation of known or suspected coronary disease. METHODS: Between 1990 and 2003, 2347 patients underwent DSE for evaluation of coronary disease at the Erasmus Medical Center. Echocardiographic images were analyzed offline using a 16-segment, 5-point scoring model for regional function. Twelve-lead resting ECGs were analyzed and patients were grouped in three categories according to their spatial QRS-T angle: normal (0-105 degrees), borderline (105-135 degrees), and abnormal (135-180 degrees). RESULTS: Mean age was 61+/-13 years, 66% were male, 32% had hypertension, 26% had hypercholesterolemia, 28% were smokers, and 12% were diabetic. During a mean follow-up of 7+/-3.4 years, 26.5% (623) of the patients died; 15.3% (359) died due to a cardiac cause. Abnormal QRS-T angle (135-180 degrees ) was present in 21% of the patients. Abnormal QRS-T angle was a predictor of cardiac death [hazard ratio: 3.2 (2.6-4.1)] and all-cause mortality [hazard ratio: 2.2 (1.8-2.6)]. After multivariate analysis abnormal and borderline QRS-T angle, peak wall motion score, age, male sex, history of diabetes, history of heart failure, smoking, and hypertension were independent predictors of (cardiac) death. CONCLUSION: Abnormal QRS-T angle is an independent predictor of (cardiac) death in patients undergoing DSE. Abnormal QRS-T angle should be considered as a risk factor in stable patients evaluated for coronary disease.

Detection of stress-induced myocardial ischemia from the depolarization phase of the cardiac cycle--a preliminary study.

BACKGROUND: Electrocardiogram (ECG)-based detection of ischemia is typically dependent on identifying changes in repolarization. Analysis of high-frequency QRS (HFQRS) components, related to the depolarization phase of the cardiac action potential, has been reported to better identify ischemia. Our aim was to test the hypothesis that HFQRS analysis is both more sensitive and specific than standard ECG for detecting exercise-induced ischemia in patients undergoing exercise myocardial perfusion imaging (MPI). METHODS: Exercise MPI was performed in 133 consecutive patients (age, 63 +/- 12; 100 males) and used as the gold standard for ischemia. Patients with QRS duration more than 120 milliseconds (n = 20), technical problems (n = 8), or inconclusive MPI (n = 4) were excluded, leaving 101 patients for analysis. Conventional ECG was combined with high-resolution ECG acquisition that was digitized and analyzed using the HyperQ System (BSP, Tel Aviv, Israel). The relative HFQRS intensity change during exercise was used as an index of ischemia. RESULTS: Of the 101 patients who were included in the analysis, 19 exhibited MPI ischemia. The HFQRS index of ischemia was found to be more sensitive (79% vs 41%; P < .05) and more specific (71% vs 57%; P < .05) than conventional ST analysis. CONCLUSIONS: The HFQRS analysis was more sensitive and specific than conventional ECG interpretation in detecting exercise-induced ischemia and exhibited enhanced diagnostic performance in both women and men. Thus, it may aid in the noninvasive diagnosis of ischemic heart disease.

High-frequency QRS electrocardiogram analysis during exercise stress testing for detecting ischemia.

INTRODUCTION: ECG stress testing is an inexpensive and non-invasive detector of myocardial ischemia; addition of high-frequency QRS analysis (HFQRS) may improve accuracy. This study compared HFQRS during exercise in patients with and without ischemia as defined by multiple criteria. MATERIAL AND METHODS: High-resolution ECGs were recorded for 139 patients undergoing T99-sestamibi/T201-thallium stress testing. Twenty-three were positive by at least two and 37 were negative for ischemia by all three of the following criteria: nuclear scan, ST-segment analysis and typical angina. Sixty-four not meeting criteria for positive or negative, six with adenosine test and nine patients with ECG recording artifacts were excluded. Mean age of the study group was 62+/-10 years, 83% were male. Ischemic patients had a higher incidence of previous myocardial infarction and coronary intervention than non-ischemic patients (74% vs. 46%; P=0.03 and 70% vs. 43%; P=0.05, respectively), but had a lower body mass index (28.7+/-5 vs. 33.0+/-8; P=0.015). HFQRS analysis consisting of signal averaging (150-250 Hz) and calculation of root mean squared values for each lead at different time points was performed and was similar between the groups. The relative change in HFQRS (RCQ) was calculated for each lead: {(maxHFQRS-minHFQRS)/maxHFQRS}. For each patient an RCQ index was calculated by averaging the two leads with the greatest RCQ value. The RCQ index was greater in ischemic vs. non-ischemic patients (45% vs. 34%; P=0.0069). CONCLUSION: Maximum decrease in HFQRS, as quantified by RCQ index, was greater in ischemic vs. non-ischemic patients. Use of the RCQ index may improve the diagnosis of ischemia during exercise stress testing.

Comprehensive hospital care improvement strategies reduce time to treatment in ST-elevation acute myocardial infarction.

BACKGROUND: Delay in treatment of patients with ST-elevation acute myocardial infarction (STEMI) has an adverse effect on patient outcomes. Limited data are available on the effectiveness of hospital care improvement strategies (HCIS) to reduce time to reperfusion by percutaneous coronary intervention (PCI). This study evaluated the combined effect of HCIS implementation to reduce door-to-balloon time in patients with STEMI. METHODS: Retrospective chart review was done for 95 consecutive patients with STEMI who underwent PCI at Charleston Area Medical Center. Patients with non-STEMI and patients transferred from other medical centers were excluded. Door-to-balloon time was defined as time from emergency department arrival to first PCI balloon inflation. A program of 3 HCIS was implemented: 1) a fast-track catheterization laboratory protocol, 2) feedback to cardiologists on their treatment times, and 3) a weekday 24-hour inhouse catheterization laboratory team. Patients were separated into groups before (n = 46), during (n = 18), and after (n = 31) HCIS implementation. RESULTS: Mean age was 60.3 +/- 13 years and 74% were male. The majority (64%) arrived by ambulance; 29% had a prehospital electrocardiogram done. Most patients presented during the day (68%) on weekdays (75%). Symptom onset-to-door time was 289 +/- 393 minutes. No significant differences were found between the groups for these variables. Door-to-PCI time in minutes was reduced in the group after versus the group before HCIS implementation (94.3 +/- 37 vs 133.5 +/- 53; P < 0.0001). CONCLUSION: Implementation of HCIS shortened door-to-PCI time for patients with STEMI by 39.2 +/- 10 minutes. Thus, HCIS may be effective in improving patient outcomes.