Background: Breast cancer is a major cause of death in occidental women. The role of metabolism in breast cancer etiology remains unclear. Metabolomics may help to elucidate novel biological pathways and identify new biomarkers to predict breast cancer long before symptoms appear. The aim of this study was to investigate whether untargeted metabolomic signatures from blood draws of healthy women could contribute to better understand and predict the long-term risk of developing breast cancer.Methods: A nested case-control study was conducted within the SU.VI.MAX prospective cohort (13 years of follow-up) to analyze baseline plasma samples of 211 incident breast cancer cases and 211 matched controls by LC/MS. Multivariable conditional logistic regression models were computed.Results: A total of 3,565 ions were detected and 1,221 were retained for statistical analysis. A total of 73 ions were associated with breast cancer risk (P < 0.01; FDR 0.2). Notably, we observed that a lower plasma level of O-succinylhomoserine (OR¼0.70, 95%CI¼[0.55-0.89]) and higher plasma levels of valine/norvaline [1.45 (1.15-1.83)], glutamine/ isoglutamine [1.
Background Predictors of high‐degree atrioventricular block (HAVB) after transcatheter aortic valve replacement (TAVR) are recognized, but the electrophysiological study's (EPS) role is still a subject to debate. The objective of our study was to determine factors associated with PPM implantation including the potential role of EPS before and/or after TAVR. Methods and results Seventy four consecutive patients (pts) were included and 21 pts (28.4%) received a PPM during the immediate postoperative follow‐ups (until Day 5): HAVB in 15 pts (71.4%), prophylactic implantation due to a documented increased HV interval ≥ 95–100 ms plus LBBB in 2 pts (9.5%), a high‐degree HV block evidenced at the EPS plus LBBB in 3 pts (14.3%) and one additional patient was implanted for AV‐block in presence of AFib (4.8%). In the multivariate model 1 including parameters before TAVR, both prosthesis diameter and PR lengthening remained significantly associated with PPM as well RBBB. In the multivariate model 2 including parameters after TAVR, only HV remained significantly associated with the risk of PPM (OR = 1.15 (1.05–1.26), p = .004). When all the significant variables in models 1 and 2 were analyzed together in model 3, only HV after TAVR remained significantly associated with an increased risk of PPM. Conclusions In this prospective observational study, it was revealed that a Day 4–5 EPS is likely to more precisely stratify the risk of PPM implantation regarding its ability to discover asymptomatic severe infra‐hisian conduction disturbances particularly in presence of LBBB. Multivariate analysis confirmed the prognostic value of HV alteration.
Background To the best of our knowledge, few studies have been performed that explore the electrophysiological differences between clockwise (CW) and counterclockwise (CCW) right atrial (RA) cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) using the high-resolution Rhythmia mapping system. Objectives. Accordingly, our prospective cohort study, sought to compare CW and CCW CTI-dependent AFL in preselected pure right AFL patients (pts) using the ultra-high-definition (ultra-HD) Rhythmia mapping system. The study also aimed to mathematically develop a cartography model based on automatic velocity RA measurements to identify electrophysiological AFL specificities. Methods and results Between October 2019 and July 2020, 33 patients were recruited. The mean age was 71±13 years old. No difference was found concerning clinical variables between CCW AFL and CW AFL or regarding left ventricular ejection fraction (LVEF) (55.5±10 vs. 56.6±12; p=0.76). The AFL cycle length was very similar (248±20 vs. 252±28 ms; p=0.6). The sinus venosus (SV) block line was present in 32/33 of cases (97%) and no significant difference was found between CCW and CW CTI AFL (100% vs. 91%; p=0.7). No line was localized in the region of the crista terminalis (CT). A superior gap was present in the posterior line in 14/31 (45.2%) but this was similarly present in CCW AFL, when compared to CW AFL (10/22 [45.5%] vs. (4/10 [40%]); p=0.9). When present, the extension of the posterior line of block was observed in 18/31 pts (58%) without significant differences between CCW and CW CI AFL (12/22 [54.5%] vs. (6/10 [60%]) (p=.9) The Eustachian ridge line of block was similarly present in both groups (82% [18/22] vs. 45.5% [5/11]; p=0.2). The absence of the Eustachian ridge line of block led to significantly slowed velocity in this area (28±10cm/s; n=8),and the velocities were similarly altered between both groups (26±10 [4/22] vs. 29.8±11cm/s [4/11]; p=0.6). We created mathematical, three-dimensional RA reconstruction-velocity model measurements. In each block localization, when the block line was absent, velocity was significantly slowed (≤20cm/s). A systematic slowdown in conduction velocity was observed at the entrance and exit of the CTI in 100% of cases. This alteration to the conduction entrance was localized at the lateral side of the CTI for the CCW AFL and at the septal side of the CTI for CW AFL. The exit-conduction alteration was localized at the CTI septal side for the CCW AFL and at the CTI lateral side for the CW AFL. The only differences between CW and CCW AFL concerned activation patterns. Conclusions The ultra-HD Rhythmia mapping system confirmed the absence of significant electrophysiological differences between CCW and CW AFL. The mechanistic posterior SV and Eustachian ridge block lines were confirmed in each arrhythmia. A systematic slowing down at the entrance and exit of the CTI was demonstrated in both CCW and CW AFL, but in reverse positions. FUNDunding Acknowledgement Type of funding sources: None.
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