Introduction: There is abundant evidence for sex differences in the diagnosis, implantation, and outcomes for cardiac resynchronization therapy (CRT) devices. Controversial data suggesting women are less likely to receive the device regardless of the greater benefit. The aim of this review is to assess sex differences in the implantation rate, clinical effectiveness, and safety of patients receiving CRT devices. Methods: We will conduct a systematic literature search of MEDLINE, Embase, and Web of Science to identify cohort studies that meet our eligibility criteria. Title and full text screening will be conducted in duplicate independently. Eligible studies report clinical effectiveness or safety of patients receiving CRT device while providing sex-disaggregated data. Implantation rate will be extracted from the baseline characteristics tables of the studies. The effectiveness outcomes include the following: all-cause death, hospitalization, peak oxygen consumption (pVO₂), quality of life (QoL), 6-min walk test, NYHA class reduction, LVEF, and heart failure hospitalization. The complication outcomes include the following: contrast-induced nephropathy, pneumothorax, pocket-related hematoma, pericardial tamponade, phrenic nerve stimulation, device infection, death, pulmonary edema, electrical storm, cardiogenic shock, and hypotension requiring resuscitation. Description of included studies will be reported in detail and outcomes will be meta-analyzed and presented using forest plots when feasible. Risk of bias will be assessed using the Newcastle-Ottawa Scale (NOS) by two review authors independently. GRADE approach will be used to assess the certainty of evidence. Discussion: The aim of this review is to determine the presence of differences in CRT implantation between women and men as well as differences in clinical effectiveness and safety of CRT after device implantation. Results from this systematic review will provide important insights into sex differences in CRT devices that could contribute to the development of sex-specific recommendations and inform policy. Systematic review registration: PROSPERO CRD42020204804

Formin Homology Proteins (Formins) are a highly conserved family of cytoskeletal regulatory proteins that participate in a diverse range of cellular processes. FMNL2 is a member of the Diaphanous-Related Formin sub-group, and previous reports suggest FMNL2’s role in filopodia assembly, force generation at lamellipodia, subcellular trafficking, cell–cell junction assembly, and focal adhesion formation. How FMNL2 is recruited to these sites of action is not well understood. To shed light on how FMNL2 activity is partitioned between subcellular locations, we used biotin proximity labeling and proteomic analysis to identify an FMNL2 interactome. The interactome identified known and new FMNL2 interacting proteins with functions related to previously described FMNL2 activities. In addition, our interactome predicts a novel connection between FMNL2 and extracellular vesicle assembly. We show directly that FMNL2 protein is present in exosomes.