Pre-Intubation Veno-Venous Extracorporeal Membrane Oxygenation in Patients at Risk for Respiratory Decompensation.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has emerged as a potential life-saving treatment for patients with acute respiratory failure. Given the accumulating literature supporting the use of VV-ECMO without therapeutic levels of anticoagulation, it might be feasible to use it for planned intubation before surgical procedures. Here, we report consecutive series of patients who underwent planned initiation of VV-ECMO, without anticoagulation, before induction of general anesthesia for anticipated difficult airways or respiratory decompensation. We describe the approach to safely initiate VV-ECMO in an awake patient. We retrospectively identified patients in a prospectively maintained database who underwent planned initiation of VV-ECMO before intubation. Standard statistical methods were used to determine post-procedure outcomes. Patients included were three men and one woman, with a mean age of 34.3 ± 10.4 years. Indications included mediastinal lymphoma, foreign body obstruction, hemoptysis, and tracheo-esophageal fistula. VV-ECMO was initiated electively for all patients, and no anticoagulation was used. The median duration of VV-ECMO support was 2.5 days (1-11 days), the median length of ventilator dependence and intensive care unit stay was 1 day (1-23 days) and 5 days (4-31 days), respectively. The median length of stay was 18.5 days (8-39 days). There were no thrombotic complications and no mortality at 30 days. Initiation of awake VV-ECMO is feasible and is safe before intubation and induction of anesthesia in patients at high risk for respiratory decompensation.

Targeting Heparin to Collagen within Extracellular Matrix Significantly Reduces Thrombogenicity and Improves Endothelialization of Decellularized Tissues.

Thrombosis within small-diameter vascular grafts limits the development of bioartificial, engineered vascular conduits, especially those derived from extracellular matrix (ECM). Here we describe an easy-to-implement strategy to chemically modify vascular ECM by covalently linking a collagen binding peptide (CBP) to heparin to form a heparin derivative (CBP-heparin) that selectively binds a subset of collagens. Modification of ECM with CBP-heparin leads to increased deposition of functional heparin (by ∼7.2-fold measured by glycosaminoglycan composition) and a corresponding reduction in platelet binding (>70%) and whole blood clotting (>80%) onto the ECM. Furthermore, addition of CBP-heparin to the ECM stabilizes long-term endothelial cell attachment to the lumen of ECM-derived vascular conduits, potentially through recruitment of heparin-binding growth factors that ultimately improve the durability of endothelialization in vitro. Overall, our findings provide a simple yet effective method to increase deposition of functional heparin on the surface of ECM-based vascular grafts and thereby minimize thrombogenicity of decellularized tissue, overcoming a significant challenge in tissue engineering of bioartificial vessels and vascularized organs.

FIP1L1-PDGFRA Clonal Hypereosinophilic Syndrome With Eosinophilic Myocarditis and Intracardiac Thrombus.

A 45-year-old man from El Salvador with no past medical history presented with cough and chest pain. Investigations revealed 60% peripheral eosinophilia (absolute count 12.3 K/uL). Cardiac imaging was consistent with myocarditis with intracardiac thrombus formation. Endomyocardial biopsy confirmed eosinophilic infiltration of the myocardium, and bone marrow biopsy showed hypercellular marrow with 28% eosinophils. Cytogenetics/fluorescence in situ hybridization (FISH) confirmed positive FIP1L1-PDGFRA rearrangement. The patient was treated for FIP1L1-PDGFRA clonal hypereosinophilic syndrome with associated eosinophilic myocarditis and intracardiac thrombus. The treatment regimen consisted of a steroid taper, imatinib, and anticoagulation. Treatment was followed by normalization of the eosinophil count. At two-year follow-up, the patient was without recurrence of eosinophilia on maintenance imatinib and indefinite anticoagulation with warfarin.

Refocusing on the Primary Prevention of Heart Failure.

PURPOSE OF REVIEW: The burden of heart failure (HF) is a significant national and global public health problem, with prevalence rates on the rise. Given the significant morbidity, mortality, and healthcare costs attributable to HF, it is of utmost importance to utilize preventive strategies to prevent the development of HF. Therefore, we sought to address how a multi-modal risk assessment approach can be used to stratify patients for HF risk and guide implementation of therapeutic strategies to prevent HF. RECENT FINDINGS: New externally validated, multivariate prediction models for incident HF can be applied in the general population and may be used to aide clinicians in assessing individualized HF risk and screening for HF. Recent clinical trial data suggest a natriuretic peptide biomarker-based screening approach coupled with team-based cardiovascular care to focus on optimization of guideline-directed medical therapy may help prevent new-onset HF. However, widespread implementation of clinical risk scores and/or biomarkers is needed. SUMMARY: In addition to promoting a heart healthy lifestyle, prevention and management of modifiable risk factors, including intensive blood pressure lowering and use of sodium-glucose cotransporter-2 inhibitors, can prevent incident HF.

Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification.

There is a need for off-the-shelf, small-diameter vascular grafts that are safe and exhibit high long-term patency. Decellularized tissues can potentially be used as vascular grafts; however, thrombogenic and unpredictable remodeling properties such as intimal hyperplasia and calcification are concerns that hinder their clinical use. The objective of this study was to investigate the long-term function and remodeling of extracellular matrix (ECM)-based vascular grafts composited with antioxidant poly(1, 8-octamethylene-citrate-co-cysteine) (POCC) with or without immobilized heparin. Rat aortas were decellularized to create the following vascular grafts: 1) ECM hybridized with POCC (Poly-ECM), 2) Poly-ECM subsequently functionalized with heparin (Poly-ECM-Hep), and 3) non-modified vascular ECM. Grafts were evaluated as interposition grafts in the abdominal aorta of adult rats at three months. All grafts displayed antioxidant activity, were patent, and exhibited minimal intramural cell infiltration with varying degrees of calcification. Areas of calcification co-localized with osteochondrogenic differentiation of vascular smooth muscle cells, lipid peroxidation, oxidized DNA damage, and cell apoptosis, suggesting an important role for oxidative stress in the calcification of grafts. The extent of calcification within grafts was inversely proportional to their antioxidant activity: Poly-ECM-Hep > ECM > Poly-ECM. The incorporation of antioxidants into vascular grafts may be a viable strategy to inhibit degenerative changes.

Mechanocompatible Polymer-Extracellular-Matrix Composites for Vascular Tissue Engineering.

Small-diameter vascular grafts developed from vascular extracellular matrix (ECM) can potentially be used for bypass surgeries and other vascular reconstruction and repair procedures. The addition of heparin to the ECM improves graft hemocompatibility but often involves chemical cross-linking, which increases ECM mechanical stiffness compared to native arteries. Herein, the importance of maintaining ECM mechanocompatibility is demonstrated, and a mechanocompatible strategy to immobilize heparin onto the ECM via a biodegradable elastomer is described. Specifically, poly(1,8-octamethylene citrate)-co-cysteine is hybridized to the ECM, forming a polymer-ECM composite that allows for heparin immobilization via maleimide-thiol "click" chemistry. Heparinized composites reduce platelet adhesion by >60% in vitro, without altering the elastic modulus of the ECM. In a rat abdominal aortic interposition model, intimal hyperplasia in heparinized mechanocompatible grafts is 65% lower when compared to ECM-only control grafts at four weeks. In contrast, grafts that are heparinized with carbodiimide chemistry exhibit increased intimal hyperplasia (4.2-fold) and increased macrophage infiltration (3.5-fold) compared to ECM-only control grafts. All grafts show similar, partial endothelial cell coverage and little to no ECM remodeling. Overall, a mechanocompatible strategy to improve ECM thromboresistance is described and the importance of ECM mechanical properties for proper in vivo graft performance is highlighted.