Interrater reproducibility of the 2016 American society of echocardiography left ventricular diastolic function guidelines.

BACKGROUND: Little data exist regarding interreader variability of diastolic measurements and their application by the 2016 American Society of Echocardiography left ventricular (LV) diastolic function guidelines. METHODS: Volunteers (n = 49) were recruited from an outpatient cardiology practice. The presence and grade of diastology dysfunction (DD) was determined by the 2016 LV diastology guideline algorithm. We determined the mean, standard deviation, coefficient of variation, and intraclass correlation coefficient (ICC) for each measurement and Fleiss K-statistic to define differences in grading DD. We determined predictors associated with disagreement of DD grade using odds ratios. RESULTS: The mean LVEF was 56%, LAVI 32 ml/m2 , and peak TR velocity was 2.3 m/s. The ICC for mitral inflow and tissue Doppler velocities were >.90, for LV volumes were .80-.86, and for LA volume was .56. The Fleiss K-value for the agreement of the presence of DD was .68 and for DD grade was .59. Variables with increased odds of disagreement were (1) at least one reader considering a TR signal uninterpretable (OR 12.0; 95% CI 1.3-109.6), (2) at least one reader assessing both LVEF 50%-55% and LAVI 29-39 ml/m2 (OR 9.3; 95% CI 1.0-87), and (3) at least one reader assessing LVEF 50-55% (OR 3.8; 95% CI 1.1-13.4). CONCLUSIONS: Using the 2016 ASE/EACVI diastology guidelines, we found excellent interrater reliability of Doppler measurements, moderate-good interrater reliability of volumetric measurements, and moderate-good but not excellent agreement for diastology grade.

TACE-dependent TGFα shedding drives triple-negative breast cancer cell invasion.

The epidermal growth factor receptor (EGFR) is frequently expressed in triple-negative breast cancer (TNBC) and is a marker of poor prognosis in this patient population. Because activating mutations in this kinase are very rare events in breast cancer, we screened breast tumor gene expression profiles to examine the distribution of EGFR ligand expression. Of the six known EGFR ligands, transforming growth factor alpha (TGFα) was expressed more highly in triple-negative breast tumors than in tumors of other subtypes. TGFα is synthesized as a transmembrane precursor requiring tumor necrosis factor alpha converting enzyme (TACE)/ADAM17-dependent proteolytic release to activate its receptor. In our study, we show that an inhibitor of this proteolytic release blocks invasion, migration and colony formation by several TNBC cell lines. Each of the effects of the drug was reversed upon expression of a soluble TGFα mutant that does not require TACE activity, implicating this growth factor as a key metalloproteinase substrate for these phenotypes. Together, these data demonstrate that TACE-dependent TGFα shedding is a key process driving EGFR activation and subsequent proliferation and invasion in TNBC cell lines.

Multimodality Imaging of the Right Ventricle.

OPINION STATEMENT: Right ventricular (RV) structure and function is clinically important in a wide range of conditions. While conventional echocardiography (echo) methods are widely used, its limitations in RV assessment due its complex geometry are well recognized. New applications of traditional echo methods as well as emerging echo techniques including 3-dimensional (3D) echo and speckle tracking strain have the potential to overcome limitations of conventional echo, though widespread clinical use remains to be seen. Volumetric methods using cardiac magnetic resonance (CMR) and computed tomography (CT) provide accurate assessment of RV function without geometric assumptions. In addition, tissue characterization imaging for myocardial scar and fat using CMR and CT provides important information regarding the RV beyond structure and function alone and has clinical applications for diagnosis and prognosis in a broad range of pathologies. Limitations also exist for these two advanced modalities including availability and patient suitability for CMR and need for contrast and radiation exposure for CT. The complementary role of each modality for the RV as well as emerging evidence for the use of each imaging method in diagnosis and management of RV pathologies is outlined in this study.

Regional hippocampal damage in heart failure.

AIMS: Heart failure (HF) patients show cognitive and mood impairments, including short-term memory loss and depression, that have an adverse impacting on quality of life and self-care management. Brain regions, including the hippocampus, a structure significantly involved in memory and mood, show injury in HF, but the integrity of specific hippocampal subregions is unclear. METHODS AND RESULTS: To assess regional hippocampal volume loss, we evaluated 17 HF patients (mean age ± SD, 54.4 ± 2.0 years; 12 male, left ventricular ejection fraction 28.3 ± 6.8%; New York Heart Association class II/III 94%/6%) and 34 healthy control subjects (52.3 ± 1.3 years; 24 male) using high-resolution T1-weighted magnetic resonance imaging and evaluated localized surface changes with morphometric procedures. Hippocampi were manually outlined, and volumes calculated from normalized tracings. Volume differences between groups were assessed by two-sample t-tests, and regional differences were assessed by surface morphometry. Patients with HF exhibited smaller hippocampal volumes than controls (right 3060 ± 146 mm(3) vs. 3478 ± 94 mm(3), P = 0.02; left 3021 ± 145 mm(3) vs. 3352 ± 98 mm(3), P = 0.06). Volume reductions were detected principally in CA1, an area integral to an array of learning and memory functions, as well as in mid to posterior CA3 and subiculum. CONCLUSION: The hippocampus shows regional volume reduction in HF, which may contribute to short-term memory loss and depression associated with the condition.