Right Ventricular Longitudinal Strain In Left Ventricular Assist Device Surgery-A Retrospective Cohort Study.

OBJECTIVES: Right ventricular (RV) failure is common after left ventricular assist device (LVAD) surgery and is associated with higher mortality. Measurement of longitudinal RV strain using speckle-tracking technology is a novel approach to quantify RV function. The authors hypothesized that depressed peak longitudinal RV strain measured by intraoperative transesophageal echocardiography (TEE) examinations would be associated with adverse outcomes after LVAD surgery. DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center. PARTICIPANTS: Following Institutional Review Board approval, the authors retrospectively identified adult patients who underwent implantation of non-pulsatile LVAD. Exclusion criteria included inadequate TEE images and device explantation within 6 months for heart transplantation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The postoperative adverse event outcome was defined as a composite of one or more of death within 6 months, ≥14 days of inotropes, mechanical RV support, or device thrombosis. Intraoperative TEE images were analyzed for peak RV free wall longitudinal strain by two blinded investigators. Simple logistic regression was used to assess the relationship between adverse outcome and the mean of the strain measurements of the two raters. Agreement between the raters was assessed by intra-class correlation (0.62) and Pearson correlation coefficient (0.63). Of the 57 subjects, 21 (37%) had an adverse outcome. The logistic regression indicated no significant association between RV peak longitudinal strain and adverse events. CONCLUSIONS: In this retrospective study of patients undergoing non-pulsatile LVAD implantation, peak longitudinal strain of the RV free wall was not associated with adverse outcomes within 6 months after surgery. Additional quantitative echocardiographic measures for intraoperative RV assessment should be explored.

Altered MicroRNA Expression Is Responsible for the Pro-Osteogenic Phenotype of Interstitial Cells in Calcified Human Aortic Valves.

BACKGROUND: The transition of aortic valve interstitial cells (AVICs) to myofibroblastic and osteoblast-like phenotypes plays a critical role in calcific aortic valve disease progression. Several microRNAs (miRs) are implicated in stem cell differentiation into osteoblast. We hypothesized that an epigenetic mechanism regulates valvular pro-osteogenic activity. This study examined miR profile in AVICs of calcified valves and identified miRs responsible for AVIC phenotypic transition. METHODS AND RESULTS: AVICs were isolated from normal and diseased valves. The miR microarray analysis revealed 14 upregulated and 12 downregulated miRs in diseased AVICs. Increased miR-486 and decreased miR-204 levels were associated with higher levels of myofibroblastic biomarker α-smooth muscle actin and osteoblastic biomarkers runt-related transcription factor 2 (Runx2) and osterix (Osx). Cotransfection of miR-486 antagomir and miR-204 mimic in diseased AVICs reduced their ability to express Runx2 and Osx. The miR-486 mimic upregulated α-smooth muscle actin expression in normal AVICs through the protein kinase B pathway and moderately elevated Runx2 and Osx levels. Knockdown of α-smooth muscle actin attenuated Runx2 and Osx expression induced by miR-486. The miR-486 mimic and miR-204 antagomir synergistically promoted Runx2 and Osx expression and calcium deposition in normal AVICs and normal aortic valve tissue. CONCLUSIONS: In AVICs of calcified valves, increased levels of miR-486 induce myofibroblastic transition to upregulate Runx2 and Osx expression and synergize with miR-204 deficiency to elevate cellular and valvular pro-osteogenic activity. These novel findings indicate that modulation of the epigenetic mechanism underlying valvular pro-osteogenic activity has therapeutic potential for prevention of calcific aortic valve disease progression.

Toll-like receptor 4-dependent microglial activation mediates spinal cord ischemia-reperfusion injury.

BACKGROUND: Paraplegia continues to complicate thoracoabdominal aortic interventions. The elusive mechanism of spinal cord ischemia-reperfusion injury has delayed the development of pharmacological adjuncts. Microglia, the resident macrophages of the central nervous system, can have pathological responses after a variety of insults. This can occur through toll-like receptor 4 (TLR-4) in stroke models. We hypothesize that spinal cord ischemia-reperfusion injury after aortic occlusion results from TLR-4-mediated microglial activation in mice. METHODS AND RESULTS: TLR-4 mutant and wild-type mice underwent aortic occlusion for 5 minutes, followed by 60 hours of reperfusion when spinal cords were removed for analysis. Spinal cord cytokine production and microglial activation were assessed at 6 and 36 hours after surgery. Isolated microglia from mutant and wild-type mice were subjected to oxygen and glucose deprivation for 24 hours, after which the expression of TLR-4 and proinflammatory cytokines was analyzed. Mice without functional TLR-4 demonstrated decreased microglial activation and cytokine production and had preserved functional outcomes and neuronal viability after thoracic aortic occlusion. After oxygen and glucose deprivation, wild-type microglia had increased TLR-4 expression and production of proinflammatory cytokines. CONCLUSIONS: The absence of functional TLR-4 attenuated neuronal injury and microglial activation after thoracic aortic occlusion in mice. Furthermore, microglial upregulation of TLR-4 occurred after oxygen and glucose deprivation, and the absence of functional TLR-4 significantly attenuated the production of proinflammatory cytokines. In conclusion, TLR-4-mediated microglia activation in the spinal cord after aortic occlusion is critical in the mechanism of paraplegia after aortic cross-clamping and may provide targets for pharmacological intervention.

Slower walking speed forecasts increased postoperative morbidity and 1-year mortality across surgical specialties.

OBJECTIVE: The purpose of this study was to determine the relationship between the Timed Up and Go test and postoperative morbidity and 1-year mortality, and to compare the Timed Up and Go to the standard-of-care surgical risk calculators for prediction of postoperative complications. METHODS: In this prospective cohort study, patients 65 years and older undergoing elective colorectal and cardiac operations with a minimum of 1-year follow-up were included. The Timed Up and Go test was performed preoperatively. This timed test starts with the subject standing from a chair, walking 10 feet, returning to the chair, and ends after the subject sits. Timed Up and Go results were grouped as fast ≤ 10 seconds, intermediate = 11-14 seconds, and slow ≥ 15 seconds. Receiver operating characteristic curves were used to compare the 3 Timed Up and Go groups to current standard-of-care surgical risk calculators at forecasting postoperative complications. RESULTS: This study included 272 subjects (mean age of 74 ± 6 years). Slower Timed Up and Go was associated with increased postoperative complications after colorectal (fast 13%, intermediate 29%, and slow 77%; P < 0.001) and cardiac (fast 11%, intermediate 26%, and slow 52%; P < 0.001) operations. Slower Timed Up and Go was associated with increased 1-year mortality following both colorectal (fast 3%, intermediate 10%, and slow 31%; P = 0.006) and cardiac (fast 2%, intermediate 3%, and slow 12%; P = 0.039) operations. Receiver operating characteristic area under curve of the Timed Up and Go and the risk calculators for the colorectal group was 0.775 (95% CI: 0.670-0.880) and 0.554 (95% CI: 0.499-0.609), and for the cardiac group was 0.684 (95% CI: 0.603-0.766) and 0.552 (95% CI: 0.477-0.626). CONCLUSIONS: Slower Timed Up and Go forecasted increased postoperative complications and 1-year mortality across surgical specialties. Regardless of operation performed, the Timed Up and Go compared favorably to the more complex risk calculators at forecasting postoperative complications.