eperfusion therapies have led to a substantial reduction in the frequency of mechanical complications of acute myocardial infarction (MI). 1,2 Recent studies estimate that following ST-elevation MI, 0.27% to 0.91% of patients develop mechanical complications; papillary muscle rupture (PMR), ventricular free-wall rupture (FWR), and ventricular septal rupture (VSR) are estimated to occur in 0.05% to 0.26% of patients, 0.01% to 0.52% of patients, and 0.17% to 0.21% of patients, respectively. 3,4 However, unfortunately, there has been no significant decrease in associated mortality rates over the past 2 decades, and patients with mechanical complications are more than 4-fold more likely to experience in-hospital mortality than those without mechanical complications. 1,3 Mechanical complications are therefore infrequent but remain an important determinant of outcomes after MI. The purpose of this review is to highlight key clinical and diagnostic findings that may assist in the early diagnosis of mechanical complications and present an update on current management strategies. FWR Clinical FeaturesThree morphologies of FWR were originally described as follows: type 1 rupture is an abrupt tear usually within the first 24 hours of MI, type 2 rupture is a slower tear with localized myocardial erosion, and type 3 rupture is a thin-walled aneurysm perforation, which usually occurs more than 7 days after MI. 5 FWR usually occurs within 7 days after MI, 6 with a mean time to diagnosis of 2.6 days in a 2018 series. 7 Early autopsy studies demonstrated that an abrupt large tear would likely lead to sudden cardiac tamponade, cardiogenic shock, and cardiac arrest, whereas a smaller, more gradual tear may be limited by thrombus formation or a compliant pericardium but with hemodynamic instability and pericardial effusion. 8 These 2 types are also described in the surgical literature as the blowout and oozing types, respectively. 7,9 In the SHOCK trial registry, 10 there was no significant sex difference in the incidence of FWR, but patients with FWR were less likely to have diabetes or a history of prior MI. It is postulated that the absence of certain cardiovascular risk factors denotes individuals who are less likely to have coronary artery disease and thus less likely to have developed collateral circulations that protect the myocardium in the setting of acute vessel occlusion.Patients with FWR may present with chest pain, restlessness, hemodynamic compromise, or cardiogenic shock (Table ). In a 2018 series, 7 more than 80% of patients presented with cardiac tamponade. FWR occurring late in the first week or beyond may also be associated with a history of straining, such as with coughing or vomiting. 11 Examination findings may be significant for a raised jugular venous IMPORTANCE Mechanical complications of acute myocardial infarction include left ventricular free-wall rupture, ventricular septal rupture, papillary muscle rupture, pseudoaneurysm, and true aneurysm. With the introduction of early reperfusion therapies, these co...

Human pre-implantation embryonic development involves extensive changes in chromatin structure and transcriptional activity. Here, we report on LiCAT-seq, a technique that enables simultaneous profiling of chromatin accessibility and gene expression with ultra-low input of cells, and map the chromatin accessibility and transcriptome landscapes for human pre-implantation embryos. We observed global difference in chromatin accessibility between sperm and all stages of embryos, finding that the accessible regions in sperm tend to occur in gene-poor genomic regions. Integrative analyses between the two datasets reveals strong association between the establishment of accessible chromatin and embryonic genome activation (EGA), and uncovers transcription factors and endogenous retrovirus (ERVs) specific to EGA. In particular, a large proportion of the early activated genes and ERVs are bound by DUX4 and become accessible as early as the 2- to 4-cell stages. Our results thus offer mechanistic insights into the molecular events inherent to human pre-implantation development.

Highlights d scRNA-seq of human biparental and uniparental embryos revealed parent-of-origin effects d 1,388 MBGs and PBGs are involved in initiation of EGA and early differentiation d Transcriptional regulatory networks uncovered key transcription factors for MBGs and PBGs d WGBS demonstrated parent-specific DNA methylation pattern in early embryos