Percutaneous Edge-to-Edge Tricuspid Valve Repair in a Patient with Cor Triatriatum Dexter: A Case Report.

BACKGROUND: Tricuspid regurgitation is gaining importance due to its high morbidity and mortality. Especially in the elderly, novel technologies in percutaneous therapies have become valuable options due to the commonly present high surgical risk. CASE PRESENTATION: We report a case of a 78-year-old female suffering from massive tricuspid regurgitation with repetitive right-sided heart failure hospitalizations. As the patient was very frail and deemed as high surgical risk, we used the TriClip® system to improve her symptomatic status. During diagnostic work-up, an additional membrane separating the right atrium, consistent with the definition of a cor triatriatum dexter, was found. Although increasing the complexity of the procedure, implantation of 3 clips with reduction of tricuspid regurgitation to a mild-to-moderate degree was achieved without any notable complications. The patient was discharged with ameliorated symptoms on the fourth postoperative day. CONCLUSIONS: Our case highlights the feasibility of percutaneous edge-to-edge tricuspid valve repair in an elderly woman with cor triatriatum dexter. Accurate echocardiographic visualization is an absolute requirement to gain access to the tricuspid valve without interacting with prevailing additional membranes.

Imaging the fibroblast growth factor receptor network on the plasma membrane with DNA-assisted single-molecule super-resolution microscopy.

Fibroblast growth factor receptors (FGFRs) are a subfamily of receptor tyrosine kinases and central players in health and disease. Following ligand binding and the formation of homo- and heteromeric complexes, FGFRs initiate a cellular response. Challenges in studying FGFR activation are inner-subfamily interactions and a complex heterogeneity of these in the cell membrane, which demand for observation techniques that can resolve individual protein complexes and that are compatible with endogenous protein levels. Here, we established an imaging and analysis pipeline for multiplexed single-molecule localization microscopy (SMLM) of the FGFR network at the plasma membrane. Using DNA-labeled primary antibodies, we visualize all four FGFRs in the same cell with near-molecular spatial resolution. From the super-resolution imaging data, we extract information on FGFR density, spatial distribution, and inner-subfamily colocalization. Our approach is straightforward and easily adaptable to other multiplexed SMLM data of membrane proteins.

The impact of moderate Aortic Valve Disease in patients undergoing MitraClip for severe MR.

BACKGROUND: High surgical risk patients presenting with severe mitral valve regurgitation (MR) and concomitant aortic valve disease are frequently a challenge for the interdisciplinary heart team meeting. If open-heart surgery for severe MR is performed, aortic stenosis (AS) or regurgitation (AR) is corrected during the same procedure if at least moderate severity of AS or AR has been confirmed. In patients with prohibitive surgical risk, optimal management strategies in the light of available transcatheter interventions still needs to be established. METHODS AND RESULTS: In this retrospective single center study, we aimed to investigate the impact of coincident moderate aortic valve disease on the outcome of patients undergoing MitraClip for severe MR. In 286 MitraClip procedures performed in our institution, 21 patients (7,3%) were identified to suffer from concomitant moderate AS and 28 patients had moderate AR (9,8%). Patients with AS were found to have a higher incidence of >moderate MR following the procedure when compared to patients without aortic valve disease (14,3% vs. 8,9%, p = 0.001). No differences between the groups were found regarding a combined endpoint of all cause deaths and heart failure hospitalizations after 1 year follow up (no aortic-valve disease vs. moderate AS: 19% vs 18%; p = 0,881 and no aortic valve disease vs moderate AR: 19% vs. 25%; p = 0.477). However, mortality was significantly higher in patients with coincidental moderate AR (3.8% patients without aortic valve disease, 5% in patients with AS, 17,9% in patients with AR; p = 0.006). CONCLUSION: According to our analysis coincidental Aortic valve stenosis may be associated with worse technical results regarding residual MR after MitraClip. Although our results regarding a combined endpoint of all-cause mortality and heart failure hospitalizations within one year of follow up were comparable between the groups, patients with moderate AR had significantly higher mortality rates. Due to the limited number of patients, our study is only hypothesis generating. Larger trials are necessary to confirm our result.

Single-Molecule Super-Resolution Microscopy Reveals Heteromeric Complexes of MET and EGFR upon Ligand Activation.

Receptor tyrosine kinases (RTKs) orchestrate cell motility and differentiation. Deregulated RTKs may promote cancer and are prime targets for specific inhibitors. Increasing evidence indicates that resistance to inhibitor treatment involves receptor cross-interactions circumventing inhibition of one RTK by activating alternative signaling pathways. Here, we used single-molecule super-resolution microscopy to simultaneously visualize single MET and epidermal growth factor receptor (EGFR) clusters in two cancer cell lines, HeLa and BT-20, in fixed and living cells. We found heteromeric receptor clusters of EGFR and MET in both cell types, promoted by ligand activation. Single-protein tracking experiments in living cells revealed that both MET and EGFR respond to their cognate as well as non-cognate ligands by slower diffusion. In summary, for the first time, we present static as well as dynamic evidence of the presence of heteromeric clusters of MET and EGFR on the cell membrane that correlates with the relative surface expression levels of the two receptors.