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The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days.Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life.By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01).Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Macrophages (MØ) were well known to play vital roles in promoting blood flow by arteriogenic induction in experimental Peripheral Arterial Disease (PAD). MØs depending on the cytokine milieu, exist in M1 or M2 polarization states (two extremes of polarization continuum). While M1-MØs are pro-inflammatory and anti-angiogenic, M2-MØs are anti-inflammatory and pro-angiogenic. We have previously demonstrated that Micro RNA-93 (Mir93) promotes angiogenesis and perfusion recovery in experimental PAD. However, the downstream mechanisms that operate in Mir93 mediated perfusion recovery in ischemic leg are not yet clear. In our current study we investigated the role of Mir93 in MØ polarization in vitro and in animal models of hind limb ischemic (HLI). We hypothesized that “Mir93 induction in ischemic muscle promotes M2-MØ polarization that improves tissue repair, survival and neovascularization in PAD” Mir93 mimic transfection in Raw264.7 (MØ cell line) significantly induced Arginase-1 (M1 marker) expression and decreased inducible Nitric oxide synthase (iNOS) (M2 marker) expression compared to negative mimic in qPCR analysis. Bone marrow derived macrophages (BMDM) from MCM7-KO (Mir93 deficient mice) express significantly higher levels of iNOS compared to littermates under hypoxia serum starvation. Monocytes isolated from the bone marrow of MCM7-KO ischemic legs express significantly higher levels of iNOS compared to littermates. Conditioned medium from Antagomir-93 treated Raw264.7 MØs and MCM7-KO BMDM significantly decreased HUVEC capillary like tube formation on matrigel compared to negative antagomir treated or littermates. Flow cytometry analysis showed that MCM7-KO mice had significantly higher levels of M1-MØs correlating with decreased capillary density compared to litter mate controls. P We conclude that Mir93 plays a crucial role in inducing MØ-M2 polarization. Increased Mir93 levels in ischemic hind limb promote M2-MØ polarization that helps in recovery of ischemic leg by tissue repair and neovascularization. Ongoing experiments are aimed to determine whether Mir93 deficient MØs can inhibit perfusion recovery in littermates and the downstream targets of Mir93 that regulate MØ polarization in HLI

The etiologies and pathology of tricuspid regurgitation may be divided into primary and secondary causes {1}. Primary or “organic” tricuspid regurgitation is due to abnormalities of the tricuspid valve leaflets, chordea tendinea, papillary muscles, or adjacent myocardium {1, 2}. More commonly, tricuspid regurgitation occurs when anatomically normal valves function abnormally due to high pressure or volume loads. This is referred to as secondary or functional tricuspid regurgitation.