Background-Data from single-center studies suggest that echocardiographic parameters of mechanical dyssynchrony may improve patient selection for cardiac resynchronization therapy (CRT). In a prospective, multicenter setting, the Predictors of Response to CRT (PROSPECT) study tested the performance of these parameters to predict CRT response. Methods and Results-Fifty-three centers in Europe, Hong Kong, and the United States enrolled 498 patients with standard CRT indications (New York Heart Association class III or IV heart failure, left ventricular ejection fraction Յ35%, QRS Ն130 ms, stable medical regimen). Twelve echocardiographic parameters of dyssynchrony, based on both conventional and tissue Doppler-based methods, were evaluated after site training in acquisition methods and blinded core laboratory analysis. Indicators of positive CRT response were improved clinical composite score and Ն15% reduction in left ventricular end-systolic volume at 6 months. Clinical composite score was improved in 69% of 426 patients, whereas left ventricular end-systolic volume decreased Ն15% in 56% of 286 patients with paired data. The ability of the 12 echocardiographic parameters to predict clinical composite score response varied widely, with sensitivity ranging from 6% to 74% and specificity ranging from 35% to 91%; for predicting left ventricular end-systolic volume response, sensitivity ranged from 9% to 77% and specificity from 31% to 93%. For all the parameters, the area under the receiver-operating characteristics curve for positive clinical or volume response to CRT was Յ0.62. There was large variability in the analysis of the dyssynchrony parameters. Conclusion-Given the modest sensitivity and specificity in this multicenter setting despite training and central analysis, no single echocardiographic measure of dyssynchrony may be recommended to improve patient selection for CRT beyond current guidelines. Efforts aimed at reducing variability arising from technical and interpretative factors may improve the predictive power of these echocardiographic parameters in a broad clinical setting. (Circulation. 2008;117: 2608-2616.)

The interpretation of wall motion is an important component of echocardiography but remains a source of variation between observers. It has been believed that automated quantification of left ventricular (LV) systolic function by measurement of LV systolic strain from speckle-tracking echocardiography might be helpful. This multicenter study of nearly 250 volunteers without evidence of cardiovascular disease showed an average LV peak systolic strain of -18.6 +/- 0.1%. Although strain was influenced by weight, blood pressure, and heart rate, these features accounted for only 16% of variance. However, there was significant segmental variation of regional strain to necessitate the use of site-specific normal ranges.

Background: N6-methyladenosine (m6A) is the most prevalent RNA epigenetic regulation in eukaryotic cells. However, understanding of m6A in colorectal cancer (CRC) is very limited. We designed this study to investigate the role of m6A in CRC.Methods: Expression level of METTL14 was extracted from public database and tissue array to investigate the clinical relevance of METTL14 in CRC. Next, gain/loss of function experiment was used to define the role of METTL14 in the progression of CRC. Moreover, transcriptomic sequencing (RNA-seq) was applied to screen the potential targets of METTL14. The specific binding between METTL14 and presumed target was verified by RNA pull-down and RNA immunoprecipitation (RIP) assay. Furthermore, rescue experiment and methylated RNA immunoprecipitation (Me-RIP) were performed to uncover the mechanism.Results: Clinically, loss of METTL14 correlated with unfavorable prognosis of CRC patients. Functionally, knockdown of METTL14 drastically enhanced proliferative and invasive ability of CRC cells in vitro and promoted tumorigenicity and metastasis in vivo. Mechanically, RNA-seq and Me-RIP identified lncRNA XIST as the downstream target of METTL14. Knockdown of METTL14 substantially abolished m6A level of XIST and augmented XIST expression. Moreover, we found that m6A-methylated XIST was recognized by YTHDF2, a m6A reader protein, to mediate the degradation of XIST. Consistently, XIST expression negatively correlated with METTL14 and YTHDF2 in CRC tissues.Conclusion: Our findings highlight the function and prognostic value of METTL14 in CRC and extend the understanding of the importance of RNA epigenetics in cancer biology.

CPFs are generally small and single, occur most often on valvular surfaces, and may be mobile, resulting in embolization. Because of the potential for embolic events, symptomatic patients, patients undergoing cardiac surgery for other lesions, and those with highly mobile and large CPFs should be considered for surgical excision.