Predictors of 30-Day Stroke and Death After Transcarotid Revascularization.

INTRODUCTION: Much of the previous robust analyses of the results associated with transcarotid revascularization (TCAR) derives from industry-sponsored trials or the Vascular Quality Initiative (VQI). This investigation was performed to identify preoperative predictors of 30-day stroke and death using institutional databases. METHODS: A retrospective analysis was performed of carotid revascularization databases created at two high-volume TCAR centers and maintained independently of the VQI carotid module between December 2015 and December 2021. The primary outcome of interest was a composite of perioperative (30-day) stroke and death. Univariate regression analyses, followed by multivariate regression analyses, were performed to identify potential predictors of adverse events. RESULTS: During the study period, 750 TCAR procedures were performed at our combined health systems, resulting in 24 (3.2%) individuals who experienced either stroke and/or death in the perioperative period. Of these, we observed nine (1.2%) mortality events and 18 (2.4%) strokes. On univariate analysis, candidate protectors of stroke/death were found to be coronary artery disease (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.18-1.01; P = 0.05) and protamine reversal (0.51; 0.21-1.21; P = 0.15). Candidate predictors of the primary outcome were anticoagulant usage (3.03; 1.26-7.24; P = 0.01), postprocedural debris in the filter (2.30; 0.97-5.43; P = 0.06), symptomatic carotid lesion (2.03; 0.90-4.50), and cardiac arrhythmia (1.98; 0.80-4.03; P = 0.14). On multivariate analysis, two predictors remained, cardiac arrhythmia (4.21; 1.10-16.16; P = 0.04) and symptomatic carotid lesion (14.49; 1.80-116.94; P = 0.01). CONCLUSIONS: A symptomatic carotid lesion, and to a lesser extent cardiac arrhythmia, are strong predictors of 30-day stroke/death after TCAR. Surgeons should be cognizant of the increased risk of adverse events in the perioperative period in these patients.

Design and Development of a Clot Burst Pressure Device to Investigate Resuscitation Strategies.

INTRODUCTION: A reduction in clot strength is a hallmark feature of trauma-induced coagulopathy. A better understanding of clot integrity can optimize resuscitation strategies. We designed a device to gauge clot strength by pressurizing fluids over a formed clot and measuring the pressure needed to dislodge the clot. We hypothesized that this device could distinguish between clots formed in hypocoagulable and hypercoagulable states by observing differences in the clot burst pressure. METHODS: Whole blood from healthy volunteers was collected into sodium citrate tubes and was treated with heparin or fibrinogen to generate clots in a hypocoagulable or hypercoagulable state, respectively. Small bore holes were drilled into polystyrene plates, and recalcified blood was pipetted into the holes. Plates were incubated at 37°C for 30 min to form clots. A pressure cap with an inlet for fluid from a syringe pump and an outlet leading to a measurement column was secured in the wells with a watertight seal. RESULTS: Clot burst pressure was normalized to individual baseline values to account for inherent differences in clot strength. The 1.0 g/L and 2.0 g/L fibrinogen groups were 1.65 ± 0.07 (P = 0.0078) and 2.26 ± 0.16 (P = 0.0078) times as strong as baseline, respectively. The 0.10, 0.15, or 0.20 USP units/mL groups were 0.388 ± 0.07 (P = 0.125), 0.31 ± 0.07 (P = 0.125), 0.21 ± 0.07 (P = 0.125) times as strong as baseline, respectively. Data were analyzed using Wilcoxon matched pairs signed rank testing. CONCLUSIONS: This device tests clot strength using burst pressure, an easily interpreted clinical parameter not measured in existing devices. Future work can test blood from trauma patients to better understand trauma pathophysiology.

Adverse events are not increased with trainee participation in transcarotid revascularization.

OBJECTIVE: To determine whether a vascular surgery trainee's participation in transcarotid revascularization (TCAR), a new technology, affects patient safety and outcomes. DESIGN: Retrospective, institutional review of our carotid database was performed. Patients who underwent TCAR were stratified based on whether a vascular trainee was present during the procedure. Relevant demographics, comorbidities, anatomical indication, perioperative courses, and adverse events in the postoperative period were captured for statistical analysis. SETTING: Data were obtained from affiliated Memorial Hermann Hospitals in Houston, Texas. PARTICIPANTS: All patients who underwent TCAR from September 2017 to January 2022 were included. RESULTS: Of 486 patients who underwent TCAR, 173 (35.6%) were performed in the presence of a trainee, and 313 (64.4%) were performed without a trainee. Subjects in the trainee cohort had more challenging anatomy, defined as a higher rate of carotid bifurcation above C2, restenotic disease, previous ipsilateral neck dissection, and neck radiation. The trainee cohort had higher rates of estimated blood loss (61.1 ± 66 vs. 35.5 ± 39 mL, p < 0.01), longer operative time (64.8 ± 30.3 vs. 57.9 ± 20.4 min, p < .01), longer cerebral blood flow reversal time (8.9 ± 6.1 vs. 7.9 ± 6.6 min, p = .01), and higher contrast administration (25.7 ± 12.0 vs. 21.1 ± 9.4 mL, p < .01). The ability to achieve technical success was similar between the two cohorts. There was no difference in the rates of cranial nerve palsy, ipsilateral stroke, hematoma, and stent thrombosis. Hospital length of stay, death (0% vs. 1.6%, p = .10), and stroke (1.1% vs. 2.8%, p = .22) were also similar between the two cohorts. CONCLUSION: Vascular surgery trainee's involvement during TCAR did not increase adverse outcomes, such as stroke and death, in the perioperative period. The results presented herein should encourage other teaching institutions to provide surgical trainees with supervised, hands-on experience during TCAR.

Microelectromechanical System Measurement of Platelet Contraction: Direct Interrogation of Myosin Light Chain Phosphorylation.

Myosin Light Chain (MLC) regulates platelet contraction through its phosphorylation by Myosin Light Chain Kinase (MLCK) or dephosphorylation by Myosin Light Chain Phosphatase (MLCP). The correlation between platelet contraction force and levels of MLC phosphorylation is unknown. We investigate the relationship between platelet contraction force and MLC phosphorylation using a novel microelectromechanical (MEMS) based clot contraction sensor (CCS). The MLCK and MLCP pair were interrogated by inhibitors and activators of platelet function. The CCS was fabricated from silicon using photolithography techniques and force was validated over a range of deflection for different chip spring constants. The force of platelet contraction measured by the clot contraction sensor (CCS) was compared to the degree of MLC phosphorylation by Western Blotting (WB) and ELISA. Stimulators of MLC phosphorylation produced higher contraction force, higher phosphorylated MLC signal in ELISA and higher intensity bands in WB. Inhibitors of MLC phosphorylation produced the opposite. Contraction force is linearly related to levels of phosphorylated MLC. Direct measurements of clot contractile force are possible using a MEMS sensor platform and correlate linearly with the degree of MLC phosphorylation during coagulation. Measured force represents the mechanical output of the actin/myosin motor in platelets regulated by myosin light chain phosphorylation.

A Novel Platelet Function Assay for Trauma.

BACKGROUND: Platelet function tests such as thrombelastography platelet mapping and impedance aggregometry have demonstrated universal platelet dysfunction in trauma patients. In this study, we introduce the measurement of platelet contraction force as a test of platelet function. We hypothesize that force will correlate with established coagulation tests such as thrombelastography, demonstrate significant differences between healthy subjects and trauma patients, and identify critically ill trauma patients. METHODS: Blood samples were prospectively collected from level 1 trauma patients at initial presentation, assayed for force of and time to contraction and compared with thrombelastography. Blood from healthy subjects was assayed to establish a reference range. Results from trauma patients were compared with healthy controls and trauma patients that died. RESULTS: The study includes one hundred trauma patients with mean age 45 y, 74% were male, and median injury severity score of 14 ± 12. Patients that survived (n = 90) demonstrated significantly elevated platelet contraction force compared with healthy controls (n = 12) (6390 ± 2340 versus 4790 ± 470 µN, P = 0.043) and trauma patients that died (n = 10) (6390 ± 2340 versus 2860 ± 1830 µN, P = 0.0001). Elapsed time to start of platelet contraction was faster in trauma patients that survived compared with healthy controls (660 ± 467 versus 1130 ± 140 s, P = 0.0022) and those that died (660 ± 470 versus 1460 ± 1340 s, P < 0.0001). CONCLUSIONS: In contrast with all existing platelet function tests reported in the literature, which report platelet dysfunction in trauma patients, contractile force demonstrates hyperfunction in surviving trauma patients and dysfunction in nonsurvivors. Platelet contraction reflects platelet metabolic reserve and thus may be a potential biomarker for survival after trauma. Contractile force warrants further investigation to predict mortality in severely injured trauma patients.

Platelet biomechanics, platelet bioenergetics, and applications to clinical practice and translational research.

The purpose of this review is to explore the relationship between platelet bioenergetics and biomechanics and how this relationship affects the clinical interpretation of platelet function devices. Recent experimental and technological advances highlight platelet bioenergetics and biomechanics as alternative avenues for collecting clinically relevant data. Platelet bioenergetics drive energy production for key biomechanical processes like adhesion, spreading, aggregation, and contraction. Platelet function devices like thromboelastography, thromboelastometry, and aggregometry measure these biomechanical processes. Platelet storage, stroke, sepsis, trauma, or the activity of antiplatelet drugs alters measures of platelet function. However, the specific mechanisms governing these alterations in platelet function and how they relate to platelet bioenergetics are still under investigation.

Transcarotid stenting of extracranial carotid artery aneurysm with covered stents and flow reversal.

Introduction: An extracranial carotid artery aneurysm (ECAA) is a rare pathology comprising <1% of all arterial aneurysms. The etiology includes trauma, previous surgery, radiation, and infection. Treatment of ECAAs has evolved from open repair to endovascular repair with stenting. Reports of endovascular repair describe the transfemoral approach; however, little more than case reports are available describing the transcarotid approach for ECAAs. In this study, we describe a cohort of patients who safely underwent transcarotid repair of ECAAs. Methods: We performed a retrospective medical record review of all cases of transcarotid stenting using covered stents for a carotid aneurysm within 11 different hospitals within the Memorial Hermann Health System from December 2019 through December 2022. Technical success is defined as coverage of the aneurysm with no endoleak. We report the patient demographics, clinical presentation, intraoperative metrics, and outcomes. Results: Seven patients underwent transcarotid covered stent placement using flow reversal for neurologic protection. Their average age was 65 years, and four of the seven patients were men. Three patients presented with pain, two with transient ischemic attack, one with stroke, and one with a pulsatile mass. Technical success was 100%. All the patients were treated with transcarotid stenting, and the average aneurysm size was 13 mm. The average operative time was 69 minutes, and the flow reversal time was 9 minutes. No postoperative stroke, myocardial infarction, or death occurred. The average length of hospital stay was 2.7 days. Conclusions: A transcarotid approach for endovascular treatment of ECAAs was safe for this cohort of patients, with no postoperative death, stroke, or myocardial infarction. Also, the technical success was 100%.

Dual Institutional Experience with Transcarotid Artery Revascularization.

INTRODUCTION: Transcarotid artery revascularization (TCAR) is a hybrid open and endovascular technique to treat carotid stenosis. The purpose of this study is to present a large cohort of patients who underwent TCAR at 2 high-volume TCAR health systems. METHODS: This study was a retrospective chart review of all instances of TCAR within the Memorial Hermann Health System and Indiana University Health, from December 2015-January 2022, using the ENROUTE Neuroprotection Device (Silk Road Medical, Sunnyvale, CA). We report patient demographics, intraoperative metrics, 30-day results and long-term results. RESULTS: In all, 750 patients underwent TCAR in the designated time period. Average patient age was 73 years, with 68% being male. Overall, 53.9% of patients had coronary artery disease, 45.4% had diabetes, and 36.9% were symptomatic. Technical success was achieved in 98.8% of patients with conversion to open endarterectomy in 1.1%. Average reverse flow time was 9.1 minutes with length of stay greater than 1 day 38%. Ipsilateral stroke rate within 30 days was 2.3% and long-term cumulative stroke rate was 3.0%. Death within 30 days occurred in 1.2% of patients and in 5.9% over long-term follow up. In all, 1% of patients required reintervention. CONCLUSIONS: TCAR is a safe and effective treatment modality for carotid artery stenotic disease. Its outcomes are similar to historical results associated with carotid endarterectomy, long considered the gold standard.

3D printing in aortic endovascular therapies.

Endovascular treatment of aortic disease, including aneurysm or dissection, is expanding at a rapid pace. Often, the specific patient anatomy in these cases is complex. Additive manufacturing, also known as three-dimensional (3D) printing, is especially useful in the treatment of aortic disease, due to its ability to manufacture physical models of complex patient anatomy. Compared to other surgical procedures, endovascular aortic repair can readily exploit the advantages of 3D printing with regard to operative planning and preoperative training. To date, there have been numerous uses of 3D printing in the treatment of aortic pathology as an adjunct in presurgical planning and as a basis for training modules for fellows and residents. In this review, we summarize the current uses of 3D printing in the endovascular management of aortic disease. We also review the process of producing these models, the limitations of their applications, and future directions of 3D printing in this field.

PLATELET FUNCTION IN TRAUMA: IS CURRENT TECHNOLOGY IN FUNCTION TESTING MISSING THE MARK IN INJURED PATIENTS?

ABSTRACT: Platelets are subcellular anucleate components of blood primarily responsible for initiating and maintaining hemostasis. After injury to a blood vessel, platelets can be activated via several pathways, resulting in changed shape, adherence to the injury site, aggregation to form a plug, degranulation to initiate activation in other nearby platelets, and acceleration of thrombin formation to convert fibrinogen to fibrin before contracting to strengthen the clot. Platelet function assays use agonists to induce and measure one or more of these processes to identify alterations in platelet function that increase the likelihood of bleeding or thrombotic events. In severe trauma, these assays have revealed that platelet dysfunction is strongly associated with poor clinical outcomes. However, to date, the mechanism(s) causing clinically significant platelet dysfunction remain poorly understood. We review the pros, cons, and evidence for use of many of the popular assays in trauma, discuss limitations of their use in this patient population, and present approaches that can be taken to develop improved functional assays capable of elucidating mechanisms of trauma-induced platelet dysfunction. Platelet dysfunction in trauma has been associated with need for transfusions and mortality; however, most of the current platelet function assays were not designed for evaluating trauma patients, and there are limited data regarding their use in this population. New or improved functional assays will help define the mechanisms by which platelet dysfunction occurs, as well as help optimize future treatment.

Procoagulant in vitro effects of clinical cellular therapeutics in a severely injured trauma population.

Clinical trials in trauma populations are exploring the use of clinical cellular therapeutics (CCTs) like human mesenchymal stromal cells (MSC) and mononuclear cells (MNC). Recent studies demonstrate a procoagulant effect of these CCTs related to their expression of tissue factor (TF). We sought to examine this relationship in blood from severely injured trauma patients and identify methods to reverse this procoagulant effect. Human MSCs from bone marrow, adipose, and amniotic tissues and freshly isolated bone marrow MNC samples were tested. TF expression and phenotype were quantified using flow cytometry. CCTs were mixed individually with trauma patients' whole blood, assayed with thromboelastography (TEG), and compared with healthy subjects mixed with the same cell sources. Heparin was added to samples at increasing concentrations until TEG parameters normalized. Clotting time or R time in TEG decreased relative to the TF expression of the CCT treatment in a logarithmic fashion for trauma patients and healthy subjects. Nonlinear regression curves were significantly different with healthy subjects demonstrating greater relative decreases in TEG clotting time. In vitro coadministration of heparin normalized the procoagulant effect and required dose escalation based on TF expression. TF expression in human MSC and MNC has a procoagulant effect in blood from trauma patients and healthy subjects. The procoagulant effect is lower in trauma patients possibly because their clotting time is already accelerated. The procoagulant effect due to MSC/MNC TF expression could be useful in the bleeding trauma patient; however, it may emerge as a safety release criterion due to thrombotic risk. The TF procoagulant effect is reversible with heparin.

TEG Lysis Shutdown Represents Coagulopathy in Bleeding Trauma Patients: Analysis of the PROPPR Cohort.

BACKGROUND: Thrombelastography (TEG) fibrinolysis shutdown after trauma is associated with increased mortality due to hypercoagulability-associated organ failure. However, a lack of mechanistic data has precluded the development of novel interventions to treat shutdown. OBJECTIVES: To define the pathophysiology of TEG shutdown in severely injured, bleeding patients through secondary analysis of the PROPPR trial. METHODS: Fibrinolysis was characterized in PROPPR subjects using admission TEG lysis at 30 min (LY30) or plasmin-antiplasmin (PAP) levels. LY30 categories were low (<0.9%), moderate (0.9-2.9%), or high (≥ 3%). PAP was classified as low (<1,500 µg/L), moderate (1,500-20,000 µg/L), or high (>20,000 µg/L). Demographics, outcomes, admission TEG values, platelet count and function, standard coagulation tests, and coagulation proteins were compared. RESULTS: Five hundred forty-seven patients had TEG data and 549 patients had PAP data available. Low LY30 was associated with reduced platelet count and aggregation, poorer TEG clot formation, prolonged clotting times, and reduced fibrinogen and alpha2 antiplasmin. Compared to moderate PAP, low PAP subjects had similar platelet parameters, TEG values, fibrinogen, and alpha2 antiplasmin, but reduced tPA, and elevated PAI-1. D-Dimer values increased as PAP increased, however patients with low LY30 had elevated D-Dimer compared with moderate LY30 patients. Most low LY30 deaths were due to TBI (45%) and hemorrhage (42%) versus one of each cause (TBI, hemorrhage, MOF) in low PAP patients. CONCLUSIONS: Low TEG LY30 does not reflect shutdown of enzymatic fibrinolysis with hypercoagulability, but rather a coagulopathic state of moderate fibrinolysis with fibrinogen consumption and platelet dysfunction that is associated with poor outcomes.

A Useful Device to Measure Kinetics of Platelet Contraction.

Platelet contraction provides a minimally invasive source for physiologic information. In this article, we describe a device that directly measures the kinetics of platelet contraction. Whole blood is injected between acrylic plates and an adherent clot forms. The bottom plate is fixed, and the top plate is attached to a wire cantilever. Platelet contraction drives deflection of the wire cantilever which is captured by a camera. Force generated by the clot with time is derived using beam equations. Force derivations were verified using a microelectromechanical (MEMS) force sensor. Kinetics of clot contraction were defined, including maximum contraction force (FMAX), lift-off time (TLIFTOFF), and contraction rate (CR). Metrics were compared with optical aggregometry and thromboelastography. FMAX correlates with optical aggregometry maximal amplitude with a Spearman's rho of 0.7904 and p = 0.0195 and thromboelastography maximal amplitude with a Spearman's rho of 0.8857 and p = 0.0188. Lift-off time correlates with optical aggregometry lag time with a Spearman's rho of 0.9048 and p = 0.002. This preliminary study demonstrates the repeatability of a useful platelet contraction device and its correlation with thromboelastography and optical aggregometry, the gold standard platelet function test.

Clinical Cellular Therapeutics Accelerate Clot Formation.

Clinical cellular therapeutics (CCTs) have shown preliminary efficacy in reducing inflammation after trauma, preserving cardiac function after myocardial infarction, and improving functional recovery after stroke. However, most clinically available cell lines express tissue factor (TF) which stimulates coagulation. We sought to define the degree of procoagulant activity of CCTs as related to TF expression. CCT samples from bone marrow, adipose, amniotic fluid, umbilical cord, multi-potent adult progenitor cell donors, and bone marrow mononuclear cells were tested. TF expression and phenotype were quantified using flow cytometry. Procoagulant activity of the CCTs was measured in vitro with thromboelastography and calibrated thrombogram. Fluorescence-activated cell sorting (FACS) separated samples into high- and low-TF expressing populations to isolate the contribution of TF to coagulation. A TF neutralizing antibody was incubated with samples to demonstrate loss of procoagulant function. All CCTs tested expressed procoagulant activity that correlated with expression of tissue factor. Time to clot and thrombin formation decreased with increasing TF expression. High-TF expressing cells decreased clotting time more than low-TF expressing cells when isolated from a single donor using FACS. A TF neutralizing antibody restored clotting time to control values in some, but not all, CCT samples. CCTs demonstrate wide variability in procoagulant activity related to TF expression. Time to clot and thrombin formation decreases as TF load increases and this procoagulant effect is neutralized by a TF blocking antibody. Clinical trials using CCTs are in progress and TF expression may emerge as a safety release criterion. Stem Cells Translational Medicine 2018;7:731-739.

The effect of damage control laparotomy on major abdominal complications: A matched analysis.

INTRODUCTION: Damage control laparotomy (DCL) for trauma is thought to be associated with increased abdominal complications. The purpose of this study is to determine the effect of DCL on abdominal complications by comparing two groups of trauma patients: DCL patients who were prospectively adjudicated to potentially being closed at the primary laparotomy (potential DEF or pDEF) and those who underwent definitive laparotomy (DEF). METHODS: The pDEF group was matched to DEF patients according to mechanism of injury, abdominal injury severity, operating room transfusions, and performance of a colon resection. The primary outcome was major abdominal complications (MAC), a composite variable. RESULTS: No statistically significant difference in the primary outcome, major abdominal complications, were seen (pDEF 19% versus DEF 56%, p = 0.066). The pDEF group was more likely to have a fascial dehiscence (38% versus 0%, p = 0.018), and to be re-opened after fascial closure (38% versus 0%, p = 0.018). CONCLUSION: Damage control laparotomy was associated with clinically but not statistically significant increase in rates of MAC. Increased numbers of patients to analyze in this fashion is needed.

Preservation of native aortic valve flow and full hemodynamic support with the TORVAD using a computational model of the cardiovascular system.

This article describes the stroke volume selection and operational design for the toroidal ventricular assist device (TORVAD), a synchronous, positive-displacement ventricular assist device (VAD). A lumped parameter model was used to simulate hemodynamics with the TORVAD compared with those under continuous-flow VAD support. Results from the simulation demonstrated that a TORVAD with a 30 ml stroke volume ejecting with an early diastolic counterpulse provides comparable systemic support to the HeartMate II (HMII) (cardiac output 5.7 L/min up from 3.1 L/min in simulated heart failure). By taking the advantage of synchronous pulsatility, the TORVAD delivers full hemodynamic support with nearly half the VAD flow rate (2.7 L/min compared with 5.3 L/min for the HMII) by allowing the left ventricle to eject during systole and thus preserving native aortic valve flow (3.0 L/min compared with 0.4 L/min for the HMII, down from 3.1 L/min at baseline). The TORVAD also preserves pulse pressure (26.7 mm Hg compared with 12.8 mm Hg for the HMII, down from 29.1 mm Hg at baseline). Preservation of aortic valve flow with synchronous pulsatile support could reduce the high incidence of aortic insufficiency and valve cusp fusion reported in patients supported with continuous-flow VADs.

Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device.

The purpose of this investigation is to use a computational model to compare a synchronized valveless pulsatile left ventricular assist device with continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate the support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous pulsatile valveless dual-piston positive displacement pump. These results were compared with measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared with the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device.