Diabetes is associated with increased ECV. Extracellular volume fraction detects amelioration of ECM expansion associated with RAAS blockade, and is associated with mortality and/or incident hospitalization for heart failure in diabetic individuals. Extracellular matrix expansion may be an important intermediate phenotype in diabetic individuals that is detectable and treatable.

Among myriad changes occurring during the apparent evolution of HFpEF where elevated BNP is prevalent, MF was similarly prevalent in those with or at risk for HFpEF. Conceivably, MF might precede clinical HFpEF diagnosis. Regardless, MF was associated with disease severity (ie, BNP) and outcomes. Whether cells and secretomes mediating MF represent therapeutic targets in HFpEF warrants further evaluation.

Background Due to anatomic and physiologic concerns, prior generations of the left ventricular assist devices (LVAD) have frequently been denied to patients with small body size. However, outcomes in patients with small body surface area (BSA) following HeartMate 3 (HM3) LVAD implantation remain relatively unknown. Methods A cohort of 220 patients implanted at a single center was divided into two groups: BSA ≤1.8 m2 (small BSA, n = 37) and BSA >1.8 m2 (large BSA, n = 183). We investigated baseline characteristics and clinical outcomes including survival and incidence of adverse events. Results Small BSA patients were older (60 vs. 57 years), more likely female (60% vs. 20%), had a lower body mass index (24 vs. 32 kg/m2), lower incidence of diabetes (32% vs. 51%), history of stroke (5% vs. 19%), and left ventricular thrombus (0% vs. 11%). They had smaller left ventricular end diastolic diameter (64.8 vs. 69.3 mm). Pump speed and pump flows at discharge were lower in the small BSA group. Survival at 1 year and 2 years was 86% versus 87% and 86% versus 79% for small versus large BSA groups (p = 0.408), respectively. The rates of adverse events were similar between groups and there were no cases of confirmed pump thrombosis. The incidence of readmissions for low flow alarms was higher in the small BSA group (0.55 vs. 0.24 EPPY). Conclusions These findings demonstrate comparable outcomes in patients with small body size and suggest that this parameter should not be an exclusion criterion on patients who are otherwise candidates for HM3 LVAD implantation.

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Objective-To determine whether increased 12/15-lipoxygenase (12/15LO) expression in vivo enhances neointimal formation in response to injury. Methods and Results-12/15LO expression in the vessel wall is increased in animal models of metabolic syndrome and diabetes mellitus. Increased expression of 12/15LO enhances cultured vascular smooth muscle cell (VSMC) proliferation, an effect mediated by the helix-loop-helix factor inhibitor of differentiation 3 (Id3). Carotid endothelial denudation was performed on apolipoprotein (Apo) E Ϫ/Ϫ , ApoE Ϫ/Ϫ /12/15LO Ϫ/Ϫ , C57BL/6, and 12/15LO-overexpressing transgenic mice. ApoE Ϫ/Ϫ /12/15LO Ϫ/Ϫ mice had attenuated and 12/15LO-overexpressing transgenic mice had enhanced neointimal formation compared with control mice. 12/15LO-overexpressing transgenic mice had greater postinjury carotid Id3 and Ki-67 expression, cell number, and fibronectin deposition compared with C57BL/6 mice. Loss of 12/15LO attenuated proliferation of cultured ApoE Ϫ/Ϫ VSMCs, whereas 12/15LO overexpression induced VSMC proliferation. Loss of Id3 enhanced immunoglobulin trascription factor (ITF)-2b binding to and activation of the p21 cip1 promoter and abrogated 12/15LO-induced VSMC proliferation. Conclusion-To our knowledge, these data are the first demonstration that increased expression of 12/15LO in the vessel wall enhances Id3-dependent cell proliferation, fibronectin deposition, and neointimal formation in response to injury. Key Words: vascular biology Ⅲ fibronectin Ⅲ helix-loop-helix motifs Ⅲ lipoxygenase Ⅲ neointima Ⅲ smooth muscle cell I ndividuals with type 2 diabetes mellitus have increased rates of restenosis after vascular interventional procedures. 1,2 Vascular smooth muscle cell (VSMC) proliferation and matrix production are key events in the process of neointimal formation (NIF) after percutaneous interventions. 3,4 Identifying the molecular mechanisms that mediate acceleration of these processes may provide important insight into strategies to attenuate restenosis in high-risk populations, such as those with type 2 diabetes.Previous studies have implicated 12/15-lipoxygenase (12/ 15LO) in the vascular response to injury. 12/15LO products of arachidonic acid, such as 12S-hydroxyeicosatetrenoic acid (HETE), 15S-HETE, and 13S-hydroperoxyoctadecadienoic acid (HPODE), are produced in VSMCs and have hypertrophic effects. 5,6 In vitro, 12/15LO inhibition attenuates hypertrophic effects of angiotensin II in VSMCs, mitogenic effects of cytokines, and chemotactic effects of platelet-derived growth factor. 5,7,8 Compared with VSMCs from C57BL/6 (BL-6) mice, VSMCs from 12/15LO-overexpressing transgenic (12/15LO-tg) mice grow faster, and VSMCs from 12/15LO Ϫ/Ϫ mice grow slower and display decreased S-phase entry in culture. 9,10 12/15LO and its products are increased in the vascular wall of animal models of atherosclerosis and injury-induced restenosis. 11 Compared with uninjured carotids, 12/15LO expression is significantly increased in rat carotids on day 12 after injury. 12 Moreover, pharmacological...

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OBJECTIVES The influence of preoperative left ventricular size in outcomes following centrifugal-flow left ventricular assist device (LVAD) implantation has not been well characterized. METHODS A cohort of 313 patients who received a centrifugal-flow LVAD at a single institution was analysed. Using a maximally selected log-rank statistic, we investigated whether a left ventricular end-diastolic dimension (LVEDD) cut-off point was associated with worse outcomes. The cohort was then divided in 2 groups based on the LVEDD cut-off point. RESULTS An LVEDD cut-off point of 59 mm was found to predict worse survival. Smaller LVEDD patients (≤59 mm, N = 52) were older and more likely to have a history of coronary artery disease compared those with a larger LVEDD (>59 mm, N = 261). Smaller LVEDD patients had lower survival compared to larger LVEDD patients (71% vs 85% at 1 year and 58% vs 80% at 2 years, P = 0.003). The need for temporary right ventricular mechanical support was significantly higher in the smaller LVEDD cohort (11.5% vs 1.9%, P = 0.002). Pump flows at time of discharge were lower in the smaller LVEDD group (3.8 vs 4.2 l/min, P = 0.005), who also had a higher incidence of late right ventricular failure (23% vs 12%, P = 0.02), higher rates of gastrointestinal bleeding (0.416 vs 0.256 events per patient-year, P = 0.025) and higher readmissions secondary to low flow alarms (0.429 vs 0.240 events per patient-year, P = 0.007). Multivariable analysis demonstrated that smaller LVEDD, older age, high BUN and high bilirubin levels were independent predictors of worse survival. CONCLUSIONS In patients receiving a centrifugal-flow LVAD, smaller preoperative LVEDD (≤59 mm) was associated with lower survival and higher incidence of adverse outcomes.