Analysis of LV lead position in cardiac resynchronization therapy using different imaging modalities.

OBJECTIVES: This study sought to evaluate whether left ventricular (LV) lead position in cardiac resynchronization therapy (CRT) can be determined by myocardial deformation imaging during LV pacing and to compare imaging techniques for analysis of LV lead position. BACKGROUND: LV lead position has a significant impact on effectiveness of CRT, but clinically applicable methods to determine LV lead position are less defined. METHODS: In 56 patients (53 +/- 5 years, 34 men) undergoing CRT, fluoroscopy and 2 myocardial deformation imaging-based approaches were applied to determine the LV lead position. Myocardial deformation imaging-based techniques were used to determine 1) the segment with maximal temporal difference of peak circumferential strain before and while on biventricular CRT; and 2) the segment with earliest peak systolic circumferential strain during pure LV pacing. Twelve-month echocardiography was performed to determine LV remodeling and improvement in function. Optimal LV lead position was defined as concordance or immediate neighboring of the determined LV lead position to the segment with latest systolic strain prior to CRT. RESULTS: LV lead position determined during LV pacing correlated to the position determined by fluoroscopy (kappa = 0.761). Patients with optimal LV lead position had greater improvement in LV ejection fraction and decrease in end-diastolic volume than those with nonoptimal LV lead position (12 +/- 4% vs. 7 +/- 3%, p < 0.001, and 28 +/- 13 ml vs. 14 +/- 8 ml, p < 0.001, respectively). Determination of the LV lead position based on myocardial deformation imaging during LV pacing showed greater discriminatory power for improvement of ejection fraction (difference optimal vs. nonoptimal lead position group: 4.64 +/- 1.01 ml; p < 0.001) than deformation imaging with biventricular pacing (3.03 +/- 1.08 ml; p = 0.007) and fluoroscopy (2.22 +/- 1.12 ml; p = 0.053). CONCLUSIONS: Myocardial deformation imaging during LV pacing allows determination of the LV lead position in CRT. Improvement in LV function and remodeling as indicators of optimal LV lead position can be best predicted by LV lead position analysis during LV pacing. (Left Ventricular Lead Position in Cardiac Resynchronization Therapy; NCT00748735).

Nuclear detection of Y-box protein-1 (YB-1) closely associates with progesterone receptor negativity and is a strong adverse survival factor in human breast cancer.

BACKGROUND: Y-box binding protein-1 (YB-1) is the prototypic member of the cold shock protein family that fulfills numerous cellular functions. In the nucleus YB-1 protein orchestrates transcription of proliferation-related genes, whereas in the cytoplasm it associates with mRNA and directs translation. In human tumor entities, such as breast, lung and prostate cancer, cellular YB-1 expression indicates poor clinical outcome, suggesting that YB-1 is an attractive marker to predict patients' prognosis and, potentially, is suitable to individualize treatment protocols. Given these predictive qualities of YB-1 detection we sought to establish a highly specific monoclonal antibody (Mab) for diagnostic testing and its characterization towards outcome prediction (relapse-free and overall survival). METHODS: Hybridoma cell generation was carried out with recombinant YB-1 protein as immunogen and Mab characterization was performed using immunoblotting and ELISA with recombinant and tagged YB-1 proteins, as well as immunohistochemistry of healthy and breast cancer specimens. Breast tumor tissue array staining results were analyzed for correlations with receptor expression and outcome parameters. RESULTS: YB-1-specific Mab F-E2G5 associates with conformational binding epitopes mapping to two domains within the N-terminal half of the protein and detects nuclear YB-1 protein by immunohistochemistry in paraffin-embedded breast cancer tissues. Prognostic evaluation of Mab F-E2G5 was performed by immunohistochemistry of a human breast cancer tissue microarray comprising 179 invasive breast cancers, 8 ductal carcinoma in situ and 37 normal breast tissue samples. Nuclear YB-1 detection in human breast cancer cells was associated with poor overall survival (p = 0.0046). We observed a close correlation between nuclear YB-1 detection and absence of progesterone receptor expression (p = 0.002), indicating that nuclear YB-1 detection marks a specific subgroup of breast cancer. Likely due to limitation of sample size Cox regression models failed to demonstrate significance for nuclear YB-1 detection as independent prognostic marker. CONCLUSION: Monoclonal YB-1 antibody F-E2G5 should be of great value for prospective studies to validate YB-1 as a novel biomarker suitable to optimize breast cancer treatment.

Impact of infarct transmurality on layer-specific impairment of myocardial function: a myocardial deformation imaging study.

AIMS: To evaluate deformation parameters of an endocardial, mid-myocardial, and epicardial myocardial layer in different transmurality of myocardial infarction and assess whether layer-specific deformation analysis allows definition of infarct transmurality. METHODS AND RESULTS: Fifty-six patients (mean age 55 +/- 9 years, 38 men) with chronic ischaemic left ventricular (LV) dysfunction underwent two-dimensional echocardiography and contrast-enhanced magnetic resonance imaging (ceMRI). The extent of myocardial infarction was determined as relative amount of hyperenhancement by ceMRI in a 16-segment LV model (0%, no infarction; 1-50%, non-transmural infarction; 51-100%, transmural infarction). On the basis of two-dimensional echocardiographic parasternal short-axis views peak systolic circumferential strain was determined for the total wall thickness and for each of three myocardial layers (endocardial, mid-myocardial, and epicardial) using an automatic frame-by-frame tracking system of acoustic echocardiographic markers (EchoPAC, GE Ultrasound). In non-transmural infarction impairment of circumferential strain was greater in the endocardial than the epicardial layer, relative reduction compared with control segments, 45% vs. 28% (P < 0.001), respectively. In transmural infarction additional impairment of circumferential strain was greater in the epicardial than the endocardial layer, relative reduction compared with non-transmural infarction 29% vs. 7% (P < 0.001), respectively. Endocardial layer circumferential strain allowed distinction of non-transmural vs. no infarction with higher accuracy than total wall thickness strain [area under the curve (AUC) 0.842 vs. 0.774, respectively, P = 0.001]. Epicardial layer circumferential strain allowed distinction of transmural from non-transmural infarction with higher accuracy than total wall thickness strain (AUC 0.819 vs. 0.762, respectively, P = 0.005). CONCLUSION: Non-transmural infarction results in greater functional impairment of the endocardial than of the epicardial myocardial layer. In transmural infarction both layers are affected similarly compared with controls. A layer-specific analysis of myocardial deformation allows accurate discrimination between different transmurality categories of myocardial infarction.