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Background: The optimal treatment strategy following a failed mitral valve repair remains unclear. This study evaluated early and long-term outcomes of redo mitral valve repair (MVr) and replacement (MVR) after prior mitral valve repair. Methods: Patients undergoing redo mitral valve surgery after prior mitral valve repair at a single institution between 2002 and 2014 were reviewed. Primary outcomes included operative mortality (30-day or in-hospital mortality) and long-term freedom from mitral valve reoperation and death. Secondary outcomes included postoperative complications.Results: 305 patients underwent redo MVr (n = 48) or MVR (n = 257) after prior mitral valve repair. Concomitant procedures included tricuspid valve repair or replacement (23%), aortic valve replacement (6%), and coronary artery bypass grafting (4%), with no differences between cohorts. 18% were performed via right mini-thoracotomy (24% MVr vs 18% MVR, P = 0.31). Unadjusted and risk-adjusted operative mortality were lower with MVr (0% vs 8%, P = 0.04). Rates of postoperative complications were similar except for blood product transfusion (35% MVr vs 59% MVR, P = 0.003) and prolonged mechanical ventilation (8% MVr vs 29% MVR, P = 0.003). Long-term freedom from mortality was comparable: 96% MVr versus 86% MVR at 1 year and 78% MVr versus 68% MVR at 5 years (P = 0.29).Conclusions: When technically feasible, mitral valve re-repair can be safely performed with outcomes comparable to MVR. K E Y W O R D Sminimally invasive, mitral valve, outcomes, reoperative surgery, repair, replacement, survival

The recognition of helical BH3 domains by Bcl-2 homology (BH) receptors plays a central role in apoptosis. The residues that determine specificity or promiscuity in this interactome are difficult to predict from structural and computational data. Using a cell free split-luciferase system, we have generated a 276 pairwise interaction map for 12 alanine mutations at the binding interface for three receptors, Bcl-xL, Bcl-2, and Mcl-1, and interrogated them against BH3 helices derived from Bad, Bak, Bid, Bik, Bim, Bmf, Hrk, and Puma. This panel, in conjunction with previous structural and functional studies, starts to provide a more comprehensive portrait of this interactome, explains promiscuity, and uncovers surprising details; for example, the Bcl-xL R139A mutation disrupts binding to all helices but the Bad-BH3 peptide, and Mcl-1 binding is particularly perturbed by only four mutations of the 12 tested (V220A, N260A, R263A, and F319A), while Bcl-xL and Bcl-2 have a more diverse set of important residues depending on the bound helix.

We validate a practical methodology for the rapid profiling of small molecule inhibitors of protein–protein interactions. We find that a well known BH3 family inhibitor can potently inhibit the p53/hDM2 interaction.

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