Layer-specific and whole wall global longitudinal strain predict major adverse cardiovascular events in patients with stable angina pectoris.

Global longitudinal strain (GLS) has proven to be a powerful prognostic marker in various patient populations, but the prognostic value of layer-specific GLS has not yet been investigated in patients with suspected stable angina pectoris (SAP). We sought to investigate the prognostic value of layer-specific and whole wall GLS in patients with suspected SAP. From September 2008 to March 2011, 296 consecutive patients with clinically suspected SAP, normal ejection fraction, and no previous cardiac history were enrolled in a prospective cohort study. Patients underwent echocardiography including two-dimensional speckle tracking at rest, exercise stress test, and coronary angiography. The end-point was a composite of incident heart failure, acute myocardial infarction, and cardiovascular death (MACE). Out of the 285 included patients (mean age 61 years, 50% male), 24 (8%) developed MACE during a median follow-up of 3.5 years. Both endocardial [hazard ratio (HR) 1.21, 95% CI 1.08-1.35, p = 0.001], epicardial (HR 1.29, 95% CI 1.12-1.50, p = 0.001) and whole wall GLS (HR 1.25, 1.10-1.42, p = 0.001) were significantly associated with an increased risk of developing MACE during follow-up in univariable Cox regression analysis. In multivariable analysis, only epicardial (HR 1.23, 95% CI 1.00-1.51, p = 0.046) and whole wall GLS (HR 1.20, 95% CI 1.00-1.43, p = 0.049) remained significantly associated with an increased risk of MACE independent of various baseline clinical variables, left ventricular ejection fraction (LVEF), E/e' and Duke Score. Layer-specific and whole wall GLS were significant predictors of MACE in this cohort of patients with suspected SAP independent of various baseline clinical variables, LVEF, E/e' and Duke Score.

Early diastolic strain rate by two-dimensional speckle tracking echocardiography is a predictor of coronary artery disease and cardiovascular events in stable angina pectoris.

This study aimed to clarify the diagnostic and prognostic potential of strain rate in patients with suspected stable angina pectoris (SAP). Strain rate by 2-dimensional speckle tracking echocardiography (2DSTE) has been suggested to be able to diagnose coronary artery disease (CAD) and predict cardiovascular events in various patient groups. Prospectively enrolled patients (n = 296) with suspected SAP, no previous cardiac disease, and normal left ventricular ejection fraction were examined by 2DSTE, exercise ECG, and coronary angiography. Obstructive CAD was defined as stenosis ≥ 70% in ≥ 1 coronary artery on coronary angiography (n = 107). Major adverse cardiac events (MACE) included myocardial infarction, heart failure, atrial fibrillation, and stroke. In multivariable analysis adjusted for baseline data, conventional echocardiography, and Duke score, early diastolic strain rate (SRe) was independently associated with significant CAD with a 1.35 increased risk of having CAD per 0.1 decrease in SRe (OR = 1.35, 95% CI 1.03-1.76, P = 0.027). Peak velocity of early diastolic filling (E)/SRe was not associated with significant CAD (OR = 1.14, 95% CI 0.81-1.62, P = 0.445). MACE occurred in 34 patients (12%) during follow-up (median 3.5 years) and both SRe (HR 1.26, 95% CI (1.07-1.49), P = 0.006) and E/SRe (HR 1.24, 95% CI (1.04-1.47), P = 0.017) were independent predictors after multivariable adjustment. In patients with suspected SAP, SRe by 2DSTE was independently associated with presence of CAD. In addition, SRe and E/SRe provided independent and incremental prognostic value for predicting future MACE.

Usefulness of layer-specific strain in diagnosis of coronary artery disease in patients with stable angina pectoris.

Novel software allows for layer-specific evaluation of myocardial strain by speckle tracking echocardiography (2DSTE). However, the potential of layer-specific strain at rest for diagnosing coronary artery disease (CAD) in patients with suspected stable angina pectoris (SAP) remains unknown. Our objective was to evaluate the usefulness of layer-specific 2DSTE at rest for diagnosis of CAD in patients with SAP. In total, 285 patients referred with clinically suspected SAP, normal ejection fraction, and no previous cardiac history were prospectively enrolled. All patients were examined by echocardiography, including 2DSTE, exercise ECG, and coronary angiography (CAG). Layer-specific 2DSTE was performed in three apical views to provide longitudinal peak systolic strains. Stenosis ≥ 70% in ≥ 1 major coronary artery on CAG was considered as significant CAD. Of 285 patients included, 104 had significant CAD (36%). Endocardial, epicardial, and mid-myocardial GLS were all significantly impaired in CAD patients (P < 0.001). Multivariable analysis including baseline clinical parameters, conventional echocardiographic measurements, Duke score, and layer-specific strain measurements revealed epicardial [odds ratio 1.19 (P = 0.048)] and mid-myocardial [odds ratio 1.16 (P = 0.047)] global longitudinal strain (GLS) as the only independent predictors of CAD. In direct comparison, epicardial and mid-myocardial GLS had a significantly higher diagnostic performance compared to endocardial GLS (P = 0.038 and P = 0.031, respectively). In conclusion, layer-specific GLS from 2DSTE at rest was significantly impaired in patients with significant CAD. In addition, epicardial and mid-myocardial GLS were independent predictors of CAD.

Gene expression in colorectal cancer.

Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226 known genes and 157 ESTs were found to be highly relevant for CRC. The alteration of known genes was confirmed in >70% of the cases by array analysis of 25 single samples. Two-way hierarchical average linkage cluster analysis clustered normal tissue together with Dukes' A, clustered Dukes' B with Dukes' C, and clustered Dukes' D separately. Real-time PCR of 10 known genes and 5 ESTs demonstrated excellent reproducibility of the array-based findings. The most frequently altered genes belonged to functional categories of metabolism (22%), transcription and translation (11%), and cellular processes (9%). Fifteen nuclear encoded mitochondrial proteins were all down-regulated in CRC. We identified several chromosomal locations with clusters of either potential oncogenes or potential tumor suppressors. Some of these, such as aminopeptidase N/CD13 and sigma B3 protein on chromosome 15q25, coincided with a high frequency of loss of heterozygosity. The genes and ESTs presented in this study encode new potential tumor markers as well as potential novel therapeutic targets for prevention or therapy of CRC.