Successful Treatment of Severe Paravalvular Leak by Repositioning a Self-Expandable Percutaneous Aortic Valve Bioprosthesis (Evolut PRO+) Using the "Double Snare" Technique.

Significant (moderate or severe) paravalvular leak (PVL) after transcatheter aortic valve replacement (TAVR) remains a common phenomenon and has been associated with decrease survival and quality of life. Transcatheter valve embolization and migration (TVEM) is a rare post-TAVR complication that can occur in 1% of cases and has been associated with worse patient outcomes. Valve embolization or migration into the left ventricle can result in significant PVL causing hemodynamic instability, shock, heart failure, and hemolytic anemia.

Small molecules that inhibit the late stage of Munc13-4-dependent secretory granule exocytosis in mast cells.

Ca-dependent secretory granule fusion with the plasma membrane is the final step for the exocytic release of inflammatory mediators, neuropeptides, and peptide hormones. Secretory cells use a similar protein machinery at late steps in the regulated secretory pathway, employing protein isoforms from the Rab, Sec1/Munc18, Munc13/CAPS, SNARE, and synaptotagmin protein families. However, no small-molecule inhibitors of secretory granule exocytosis that target these proteins are currently available but could have clinical utility.