Search

Left ventricular assist devices (LVADs) have been used as a standard treatment option for patients with advanced heart failure. However, these devices are prone to adverse events. Nonsurgical bleeding (NSB) is the most common complication in patients with continuous flow (CF) LVADs. The development of acquired von Willebrand syndrome (AVWS) in CF-LVAD recipients is thought to be a key factor. However, AVWS is seen across a majority of LVAD patients, not just those with NSB. The purpose of this study was to examine the link between acquired platelet defects and NSB in CF-LVAD patients.Blood samples were collected from 62 CF-LVAD patients at pre- and 4 post-implantation timepoints. Reduced adhesion receptor expression (GPIbα and GPVI) and activation of platelets (GPIIb/IIIa activation) were used as markers for acquired platelet defects.Twenty-three patients experienced at least one NSB episode. Significantly higher levels of platelet activation and receptor reduction were seen in the postimplantation blood samples from bleeders compared with non-bleeders. All patients experienced the loss of high molecular weight monomers (HMWM) of von Willebrand Factor (vWF), but no difference was seen between the two groups. Multivariable logistic regression showed that biomarkers for reduced platelet receptor expression (GPIbα and GPVI) and activation (GPIIb/IIIa) have more predictive power for NSB, with the area under curve (AUC) values of 0.72, 0.68, and 0.62, respectively, than the loss of HMWM of vWF (AUC: 0.57).The data from this study indicated that the severity of acquired platelet defects has a direct link to NSB in CF-LVAD recipients.

Borreliella burgdorferi is a bacterial pathogen with limited metabolic and genomic repertoires. B. burgdorferi transits extracellularly between vertebrates and ticks and dramatically remodels its transcriptional profile to survive in disparate environments during infection. A focus of B. burgdorferi studies is to clearly understand how the bacteria responds to its environment through transcriptional changes. In vitro transcription assays allow for the basic mechanisms of transcriptional regulation to be biochemically dissected. Here, we present a detailed protocol describing B. burgdorferi RNA polymerase purification and storage, sigma factor purification, DNA template generation, and in vitro transcription assays. The protocol describes the use of RNA polymerase purified from B. burgdorferi 5A4 RpoC-His (5A4-RpoC). 5A4-RpoC is a previously published strain harboring a 10XHis-tag on the rpoC gene encoding the largest subunit of the RNA polymerase. In vitro transcription assays consist of the RNA polymerase purified from strain 5A4-RpoC, a recombinant version of the housekeeping sigma factor RpoD, and a PCR-generated double-stranded DNA template. While the protein purification techniques and approaches to assembling in vitro transcription assays are conceptually well understood and relatively common, handling considerations for RNA polymerases often differ from organism to organism. The protocol presented here is designed for enzymatic studies on the B. burgdorferi RNA polymerase. The method can be adapted to test the role of transcription factors, promoters, and post-translational modifications on the activity of the RNA polymerase.

Objective We have observed that minimally invasive left ventricular assist device (LVAD) insertion leads to more facile re-entry and easier cardiac transplantation. We hypothesize minimally invasive LVAD implantation results in improved outcomes at the time of subsequent heart transplant. Methods All adults undergoing cardiac transplantation between October 2015 and March 2019 at our institution were retrospectively reviewed. Those bridged to transplantation with a HeartWare HVAD were identified and divided into 2 cohorts based upon the surgical approach: those who underwent HVAD placement by conventional sternotomy versus minimally invasive insertion via lateral thoracotomy and hemisternotomy (LTHS). Patient demographics, as well as perioperative transplant outcomes, including survival, length of stay (LOS), blood utilization, ischemic time, bypass time, and postoperative extracorporeal membrane oxygenation (ECMO) were compared between cohorts. Results Forty-two patients were bridged to heart transplant with a HVAD implanted via either sternotomy ( n = 22) or LTHS technique ( n = 20). Demographics were similar between groups. There was 1 predischarge death in the sternotomy group and none in the LTHS group. Body surface area, cardiopulmonary bypass time, ischemic time, ECMO utilization, and reoperation for bleeding were similar. Red blood cell units transfused were significantly lower in the LTHS cohort (3.0 [1.0-5.0] vs 6.0 [2.5-10.0] P = 0.046). The LTHS cohort had a significantly shorter hospital LOS (12.0 [11.0-28.0] vs 22.5 [15.7-41.7] P = 0.022) with a trend toward shorter intensive care unit LOS (6.0 [5.0-10.5] vs 11.0 [6.0-21.5] days P = 0.057). Conclusions Minimally invasive HVAD implantation improves outcomes at subsequent heart transplantation, resulting in shorter LOS and less red cell transfusion. Larger multi-institutional studies are necessary to validate these findings.

Gastrointestinal bleeding (GIB) is a frequent complication in patients with continuous-flow left ventricular assist devices (LVAD). We retrospectively evaluated eight patients implanted with a HeartWare LVAD between July 2017 and June 2020 who experienced at least one episode of GIB and were started on tamoxifen 20 mg once daily for secondary prevention. Tamoxifen was associated with a significant decrease in major GIB from a median of 3 (IQR 1.4–7) events/patient-year pre-tamoxifen initiation to 0 (IQR 0–0.9) events/patient-year post-tamoxifen initiation (p = 0.02). Transfusion of packed red blood cells also decreased from 16.8 (IQR 9.9–30.6) units/patient-year pre-tamoxifen initiation to 1.5 (IQR 0–7.5) units/patient-year post-tamoxifen (p = 0.04). Tamoxifen was well tolerated and no thromboembolic complications were observed. This small cohort study suggests that tamoxifen is associated with reduced GIB and transfusion requirements, with no apparent increase in thrombotic risk. A larger, randomized study is warranted to confirm the results of this exploratory analysis.

Background Despite improved survival and morbidity after durable left ventricular assist device (dLVAD), outcomes for cardiogenic shock patients are suboptimal. Temporary mechanical circulatory support (tMCS) can permit optimization before dLVAD. Excellent outcomes have been observed using minimally-invasive dLVAD implantation. However, some feel tMCS contraindicates this approach. To evaluate whether left thoracotomy/hemisternotomy (LTHS) dLVAD placement is safe in this setting, we compared patients who did and did not require tMCS. Methods Outcomes for patients receiving dLVADs via LTHS were compared among those bridged with extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), or no tMCS. We evaluated demographics, comorbidities, laboratory and hemodynamic data, and intraoperative and postoperative outcomes. Results Eighty-three patients underwent LTHS dLVAD placement. Fifty did not require tMCS, while 22 (26%) required IABP, and 11 (13%) ECMO. Non-tMCS patients were primarily Intermacs 3 (56%), while IABP recipients were mainly Intermacs 2 (45%). All patients with ECMO were Intermacs 1. Patients with tMCS had worse end-organ function. Operative outcomes were similar except more concomitant procedures and red-cell transfusions in patients with ECMO. Intensive care unit and hospital length of stay and inotrope duration were also similar. There were no differences in bleeding, stroke, and infection rates. Three- and 12-month survival were: no tMCS: 94%, 86%; IABP: 100%, 88%; and ECMO: 81%, 81% (P = .45). Conclusions Patients with cardiogenic shock can safely undergo LTHS dLVAD implantation after stabilization with ECMO or IABP. Outcomes and complications in these patients were comparable to a less severely ill cohort without tMCS.

Objective Despite improvement in outcomes after left ventricular assist device (LVAD) implantation over the past 2 decades, high-risk recipients continue to have a prohibitive rate of morbidity and mortality. We hypothesized that a less invasive approach to LVAD implantation would be associated with improved survival compared to a conventional approach in this high-risk cohort. Methods All consecutive LVAD recipients (2013 to 2017) that underwent centrifugal LVAD implantation were retrospectively reviewed. Patients were classified as high-risk if INTERMACS 1 or required temporary VAD/venoarterial extracorporeal membrane oxygenation prior to durable VAD implantation. Patients were stratified into 3 groups: left thoracotomy with hemi-sternotomy (LTHS) high-risk, conventional sternotomy (CS) high-risk, and non-high-risk. The primary outcome was 1-year survival. Results A total of 57 patients (LTHS high-risk: 11, CS high-risk: 12, non-high-risk: 34) were identified. Preoperative right ventricular failure scores, HeartMate-II mortality scores, and end-organ dysfunction were similar between the 2 high-risk groups. While operative time was similar between the 3 groups, cardiopulmonary bypass time was significantly shorter in the LTHS high-risk group compared to other groups. There was a trend toward decreased intensive care unit length of stay and ventilator time in LTHS high-risk compared to CS high-risk patients. Moreover, between these 2 groups, there was a significant decrease in temporary right VAD support (50% vs 0%, P = 0.014), and 1-year survival was significantly higher in the LTHS group (42% vs 91%, P = 0.025). Conclusions Less invasive LVAD implantation appears to be associated with improved survival compared to conventional LVAD implantation in high-risk patients.

Permalloy ( Ni 0.80 Fe 0.20 , or Py) is one of the most thoroughly studied magnetic materials, with well documented properties. By fabricating ferromagnetic alloys between Copper and Py, the values of the exchange stiffness parameter, A ex , and the saturation magnetization, 4 π M s , can be controllably adjusted. This proves a simple method for engineering the magnetic properties of materials. Using Brillouin Light Scattering and Broadband Ferromagnetic Resonance techniques, we show that varying the concentration x of Cu in an alloy Cu x Py 1 - x from x = 0.00 to x = 0.37 , the saturation magnetization, 4 π M s , can be adjusted from 9.46 kOe to 4.21 kOe. Simultaneously, the exchange stiffness parameter, A ex , can be adjusted from 1.115 μerg cm−1 to 0.122 μerg cm−1.

There are no evidence-based guidelines for antithrombotic therapy in left ventricular assist device patients. We evaluated the efficacy of a multi-agent, test-guided protocol, which remained consistent throughout our use of the Heartware HVAD. Thrombelastography and platelet function analyzer (PFA)-100 guide antiplatelet titration. Goals are normal kaolin thrombelastography maximum amplitude and prolonged PFA-100. We analyzed incidence and rates of nonprocedural bleeding, stroke, and pump thrombosis for all 81 primary Heartware left ventricular assist devices implanted since 2011. For each event, we examined whether each test was within goal range. We also compared medication burden and dosage between patients with and without events. Pump thrombosis and hemorrhagic stroke each occurred in two patients (2.5%; 0.03 events/patient-year [EPPY]), and ischemic stroke in six (7.4%; 0.10 EPPY). Nonprocedural bleeding occurred 75 times in 34 patients (42%; 1.24 EPPY), primarily gastrointestinal (28%; 0.66 EPPY). Subtherapeutic international normalized ratio (INR) was the most common at thrombotic events; supratherapeutic partial thromboplastin time, international normalized ratio (INR), and PFA-adenosine diphosphate (ADP) were common at bleeding events. Medication burden and dosage were lower in patients with events than in stable patients. Protocol-guided antithrombotic therapy resulted in low rates of pump thrombosis and hemorrhagic stroke. Ischemic stroke and gastrointestinal bleeding rates were higher than in a comparable HVAD population. Optimization of our protocol to decrease its complexity and to reduce bleeding is underway.

Significant residual mitral regurgitation (MR) after left ventricular assist device (LVAD) implantation has been associated with increased morbidity and mortality. The effect of cannula position on improvement of preexisting MR has yet to be evaluated. Consecutive patients who underwent centrifugal LVAD implantation with >mild preoperative MR and without concomitant mitral repair were reviewed. Left ventricular assist device position was determined by the angle between actual and ideal inflow cannula on computed tomography. The magnitudes of angles (anterior and lateral angle) were added to form an LVAD position assessment (LVADpa). Mitral regurgitation was numerically classified, and improvement in MR was determined by difference in MR preoperatively to MR >1 month postoperatively with a median of 162 (interquartile range: 78-218) days. The primary analysis examined the relationship between LVADpa and postoperative MR. Forty-one patients were identified with >mild preoperative functional MR. Mean age was 51 ± 13 years with an ejection fraction of 16 ± 4%. Overall, MR improved from moderate-severe preoperatively to mild postoperatively (p < 0.001). On multivariable analysis, higher LVADpa deviation was associated with greater postoperative MR (odds ratio [OR] = 2.29, p = 0.005) and higher 1-month pulsatility index was associated with lower postoperative MR (OR = 0.47, p = 0.011). Inflow cannula position during centrifugal LVAD implantation is an important determinant of postoperative MR.

Gastrointestinal bleeding (GIB) is a frequent complication in patients with continuous-flow left ventricular assist devices (LVAD). We retrospectively evaluated eight patients implanted with a HeartWare LVAD between July 2017 and June 2020 who experienced at least one episode of GIB and were started on tamoxifen 20 mg once daily for secondary prevention. Tamoxifen was associated with a significant decrease in major GIB from a median of 3 (IQR 1.4-7) events/patient-year pre-tamoxifen initiation to 0 (IQR 0-0.9) events/patient-year post-tamoxifen initiation (p = 0.02). Transfusion of packed red blood cells also decreased from 16.8 (IQR 9.9-30.6) units/patient-year pre-tamoxifen initiation to 1.5 (IQR 0-7.5) units/patient-year post-tamoxifen (p = 0.04). Tamoxifen was well tolerated and no thromboembolic complications were observed. This small cohort study suggests that tamoxifen is associated with reduced GIB and transfusion requirements, with no apparent increase in thrombotic risk. A larger, randomized study is warranted to confirm the results of this exploratory analysis. Graphical abstract.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is effective for resuscitating patients in cardiogenic shock prior to committing to durable mechanical circulatory support. However, patients with severely impaired left ventricular function can develop left ventricular (LV) distension and subsequent pulmonary edema while on VA-ECMO. A percutaneous atrial septostomy can be used to allow left-sided decompression and ameliorate refractory pulmonary edema in this situation. Closure of septal defects is mandatory at the time of left ventricular assist device (LVAD) insertion to avoid right-to-left shunting and refractory hypoxemia. Here we present a case of a patient who required VA-ECMO for cardiogenic shock due to decompensated heart failure. While on VA-ECMO, he developed pulmonary edema, which resolved after a percutaneous atrial septostomy was created. Concurrent transcatheter closure of the atrial septostomy facilitated successful use of a minimally invasive approach to LVAD insertion.

Purpose To assess the utility of 18-F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging to diagnose left ventricular assist device (LVAD) infection in patients before positive microbiological cultures. Methods All patients implanted with LVADs between 10/2009 and 10/2019 aged ≥ 18 years old who underwent FDG PET/CT imaging (n=79 patients, n=119 scans) at a single center were retrospectively reviewed. Patients with positive PET/CT were identified and categorized based on microbiological culture results preceding FDG PET/CT. Medical and/or surgical intervention and outcomes were specified in all cases. Positive PET/CT was defined as evidence of FDG uptake along any part of the LVAD. Results 47 patients with increased glucose uptake associated with LVAD components were identified. 17 had prior negative cultures. Of these, four subsequently had definitive diagnosis of LVAD infection by culture of the pump pocket (n=2), driveline exit site (n=3), or blood stream (n=3) (Table 1). There was one patient with positive cultures from the pump pocket and driveline exit site despite negative PET/CT. Conclusion Our results indicate that FDG PET/CT has potential to diagnose early LVAD infection, which would increase the likelihood of successful medical, rather than surgical, management. 13 patients who had negative cultures and positive scans were attributed to peri-operative inflammation. A more robust distinction between diffuse uptake secondary to inflammation and intense focal uptake representative of infection would likely decrease prevalence of false positive results. Future work will investigate this, as well as a potential modality in machine learning image analysis, to more precisely quantify infection signal of LVAD PET/CT.

Non-surgical bleeding (NSB) is the most common clinical complication in heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). In this study, oxidative stress and alteration of signal pathways leading to platelet apoptosis were investigated. Thirty-one HF patients supported by CF-LVADs were divided into bleeder (n = 12) and non-bleeder (n = 19) groups. Multiple blood samples were collected at pre-implant (baseline) and weekly up to 1-month post-implant. A single blood sample was collected from healthy subjects (reference). Production of reactive oxygen species (ROS) in platelets, total antioxidant capacity (TAC), oxidized low-density lipoproteins (oxLDL), expression of Bcl-2 and Bcl-xL, Bax and release of cytochrome c (Cyt.c), platelet mitochondrial membrane potential (Δψ m), activation of caspases, gelsolin cleavage and platelet apoptosis were examined. Significantly elevated ROS, oxLDL and depleted TAC were evident in the bleeder group compared to non-bleeder group (p

Research has shown that family structure changes negatively influence educational attainment, but they overlook qualitative distinctions in college choice, such as college selectivity. Yet, college choice research has largely focused on static measures of family structure, failing to account for year-to-year family structure changes that occur during high school. We merge literature in family and college choice to investigate the role of family-life events on college choice. We found family structure changes that occur early and late in high school influence the selectivity of the college where a student applies, and this relation persists in spite of controls for race, gender, family background, and pre-high school family structures. Including educational expectations, parent–student discussions, and coursework rigor account for the negative association between family structure changes during high school and the selectivity of the college where a student applies. However, late family structure changes during high school continue to correlate negatively with a student’s college enrollment, potentially reflecting realities and financial burdens of attending college, especially selective colleges.

Minimally invasive approaches for left ventricular assist device (LVAD) implantation have grown in popularity and have many potential advantages including less bleeding, shorter recovery time, and improved postoperative right ventricular function when compared to traditional implantation. Centrifugal flow LVADs are easily implanted via a minimally invasive approach. In this article, the authors review intraoperive considerations for minimally invasive LVAD implantation, as well as hemodynamic management principles for patients with centrifugal flow LVADs.

BACKGROUND Obesity and heart failure rates continue to rise, confronting heart failure centers with challenging left ventricular assist device (LVAD) implantations. Although less invasive approaches to implantation have been successfully implemented by many centers, this surgical approach has not yet been well evaluated in the obese population. Therefore, we sought to describe our experience with less invasive device implantation in this patient cohort. METHODS All implants of centrifugal ventricular assist devices were retrospectively reviewed. Patients implanted with a less invasive approach via a left thoracotomy and upper hemisternotomy were included. Patients were stratified by body mass index (

In patients with intraluminal thrombus, commonly applied temporary circulatory support modalities are contraindicated secondary to concern regarding distal or proximal (specifically veno-arterial extracorporeal membrane oxygenation) embolization of the thrombus. Therefore, in patients with cardiogenic shock and synchronous intraluminal descending aortic thrombus, support options are quite limited. We report a case of a 66-year-old man in cardiogenic shock, due to an ischemic cardiomyopathy, who also had intramural thrombus with an intraluminal component in the descending thoracic aorta. An endovascular stent graft was inserted inside the aorta over the location of the mural thrombus. This allowed for the placement of an intra-aortic balloon pump (IABP) for pre-operative optimization. After 3 days, a left ventricular assist device (LVAD) was implanted via left anterolateral thoracotomy with hemi-sternotomy, and the IABP was removed. Post-operatively, he had a relatively uncomplicated course without signs of embolic phenomena and ultimately was discharged home. Surveillance computed tomography imaging at 6 months showed no endovascular leak or migration of the stent. This case demonstrates the feasibility of aortic stent graft placement to allow safe insertion of an IABP in the setting of aortic mural thrombus. Furthermore, it demonstrates the safety and feasibility of LVAD implantation after recent aortic stent graft placement.

The Laboratoire d’Astrophysique de Marseille (LAM) is deeply involved in the development and the test of the NISP (Near Infrared Spectro-Photometer) instrument for the ESA EUCLID mission that will be launched in 2020. The goal of the mission is to understand the nature of the dark energy responsible for the accelerating expansion of the Universe. NISP is one of its two instruments operating in the near-IR spectral region (0.9-2μm) to map the geometry of the dark Universe. The integration of the NISP flight model (FM) has been started at LAM to allow its delivery in 2019 to the payload after vibration test and two thermal vacuum test campaigns to demonstrate the performance of the instrument. The thermal vacuum test will take place in ERIOS chamber, a 90m3 chamber developed by LAM to test optical instruments at cryogenics temperature and high vacuum. In addition to the chamber, a full and specialised set of ground support equipment called the Verification Ground System (VGS) is developed to fill the goal of the NISP test campaign. The test campaign combines functional tests of the detectors and wheels, performance tests of the instrument, calibration procedure validation and observations scenario test, all done at LAM. One of the main objectives of the test campaign is the measurement of NISP focus position with respect to the EUCLID object plane. The VGS is made of i) a telescope simulator to simulate the EUCLID telescope for optical performance tests, ii) a thermal environment to simulate the Euclid PLM thermal interfaces, iii) the NISP Electrical GSE (EGSE) to control the instrument during the test and iv) a Metrology Verification System (MVS) to measure the positions of NISP and the telescope simulator during the test. We present the set of GSE developed for NISP and their performance already validated during two blank tests: thermal blank test and metrology blank test. In addition, a blank test with all the VGS parts (thermal, optical, metrology) is scheduled in the coming months to validate the overall performance of this GSE including the telescope simulator. The goal is to measure with a high precision the focus distance of the telescope simulator at cold and the stability of the focus in time, and to demonstrate the functionality of the telescope simulator for NISP test campaign needs. Finally, we describe the thermal vacuum test configuration for the “end to end� test on the NISP flight model foreseen by beginning of 2019.

A new, insensitive nitroguanidyl functionalized nitrogen-rich material derived from 2,4-dinitrophenyl derivative was synthesized. N-2,4-dinitrophenyl-N1-nitroguanidine (DNP-NQ) has a crystal density of 1.74 g/cm3. The synthesis and properties of DNP-NQ are described. DNP-NQ was characterized by nuclear magnetic resonance (NMR), infrared spectroscopy, and gas pycnometry. Thermal properties were studied by differential scanning calorimetry (DSC). Results from small-scale sensitivity tests indicate that DNP-NQ is less sensitive than Cyclotrimethylenetrinitramine (RDX). DNP-NQ can be prepared in high yield.

Several homemade or improvised explosive mixtures that either contained volatile components or produced volatile products were examined using standard small-scale safety and thermal (SSST) testing that employed differential scanning calorimetry (DSC) techniques (constant heating rate and standard sample holders). KClO3 and KClO4 mixtures with dodecane exhibited different enthalpy behavior when using a vented sample holder in contrast to a sealed sample holder. The standard configuration produced profiles that exhibited only endothermic transitions. The sealed system produced profiles that exhibited additional exothermic transitions absent in the standard configuration produced profiles. When H2O2/fuel mixtures were examined, the volatilization of the peroxide (endothermic) dominated the profiles. When a sealed sample holder was used, the energetic releases of the mixture could be clearly observed. For AN and AN mixtures, the high temperature decomposition appears as an intense endothermic event. Using a nominally sealed sample holder also did not adequately contain the system. Only when a high-pressure rated sample holder was used the high temperature decomposition of the AN could be detected as an exothermic release. The testing was conducted during a proficiency (or round-robin type) test that included three U.S. Department of Energy and two U.S. Department of Defense laboratories. In the course ofmore » this proficiency test, certain HMEs exhibited thermal behavior that was not adequately accounted for by standard techniques. Further examination of this atypical behavior highlighted issues that may have not been recognized previously because some of these materials are not routinely tested. More importantly, if not recognized, the SSST testing results could lead to inaccurate safety assessments. Furthermore, this study provides examples, where standard techniques can be applied, and results can be obtained, but these results may be misleading in establishing thermal properties.« less

Objectives Severe renal insufficiency is considered a relative contraindication to left ventricular assist device (LVAD) implantation. After establishing an algorithmic approach to these patients, we hypothesized that LVAD implantation with severe renal insufficiency could be performed without increasing morbidity or mortality. Methods All consecutive patients (July 2015-December 2017) who underwent LVAD implantation were retrospectively reviewed. Patients were stratified by preoperative glomerular filtration rate (GFR): ≤30 mL/min/1.73 m2 (low-GFR) and >30 mL/min/1.73 m2 (high-GFR). Preoperative optimization included aggressive inotropic support and temporary mechanical circulatory support before LVAD implantation in any patient with an acute component of renal insufficiency. All patients with a preoperative GFR ≤15 mL/min/1.73 m2 were prophylactically initiated on temporary renal replacement therapy postoperatively. The primary outcome was Kaplan-Meier 1-year survival. Results Fifty-eight patients (21 with low-GFR and 37 with high-GFR) were identified. Patients in the low-GFR cohort had a significantly higher median Interagency Registry for Mechanically Assisted Circulatory Support score and worse preoperative end-organ function. Preoperative optimization resulted in an increase in GFR to >30 mL/min/1.73 m2 in 11 out of 21 patients from the low-GFR cohort. Inotrope days, ventilator time, intensive care unit length of stay, and hospital length of stay were not significantly different between the groups. Kaplan-Meier 1-year survival was 81% in the low-GFR cohort and 86% in the high-GFR cohort (P = .98). Subset analysis of GFR ≤15 mL/min/1.73 m2 (n = 11) and ≥60 mL/min/1.73 m2 (n = 19) demonstrated identical 1-year survival (89% vs 89%; P = .91). Conclusions LVAD implantation in carefully selected patients with severe renal insufficiency can be performed without increasing midterm morbidity or mortality. This strategy may serve as a successful option to bridge patients to transplantation or destination therapy.

Purpose Blood pressure (BP) control reduces stroke in LVAD patients. Home monitoring is key for optimal control. Measurement by Doppler is the most reliable non-invasive method. No study assessed the feasibility of Doppler BP obtained by LVAD patients and caregivers. Methods From 3-11/2018, 12 ambulatory patients with Heartware HVAD were recruited and taught to measure BP in 7 steps (1: quiet sitting, 2: cuff placement, 3: find radial artery flow, 4: inflate cuff, 5: deflate cuff, 6: find BP, 7: record BP). All received manual cuffs and Dopplers to check BP up to 3 times/day for 6 weeks, and had weekly reminder phone calls. They were observed to check BP at routine visits, and completed a survey at end of study. We made no medication changes based on home BP. Results Seven patients (median age 57yrs [IQ 44-67], median VAD support 39 days [IQ 32-48], 1 on support for > 1yr) completed the study. Median number of recorded BP was 42 (IQ 22-78). At enrollment, 4 patients easily learned 7 steps, 2 needed reteaching for step 3 or 5, and 1 needed reteaching for both. At follow-up, all completed 7 steps and obtained BP that modestly agreed with BP measured by staff (κ=0.25, 31% agreement, p=0.0002). Diurnal variation (higher afternoon BP) was seen in 2 patients; the rest had no change from morning to evening (Figure). Reasons for BP check failure were “forgetfulness”, “too busy”, “too sick”, or “no help/did not seek help”. Of the 5 patients who dropped out (median age 38yrs, support duration > 9 months), 3 needed reteaching for steps 3-6. Of the 2 patients who easily learned the steps, 1 lost caregiver and was hospitalized too frequently, the other was non-compliant. No one completely failed BP education after reteaching. Conclusion This pilot study demonstrated feasibility of home BP monitoring by Doppler in select patients. Those who failed to obtain daily BP checks tended to have poor social support or were not proficient in the 7-step method. Further data are needed to define and prognosticate diurnal BP variation in LVAD patients.

OBJECTIVES Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation continues to be a morbid complication. In this study, we hypothesized that a less invasive approach to implantation would preserve RV function relative to a conventional sternotomy (CS) approach. METHODS All patients (2013–2017) who underwent LVAD implantation were reviewed. Patients were stratified by surgical approach: less invasive left thoracotomy with hemi-sternotomy (LTHS) and CS. The primary outcome was severe RV failure. RESULTS Eighty-three patients (LTHS: 37, CS: 46) were identified. The median Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score was significantly worse in the LTHS compared to the CS cohort, and there was a trend towards higher RV failure scores and HeartMate II mortality scores. Preoperative RV dysfunction, in pulmonary artery pulsatility index and RV stroke work index were similar between the 2 groups. Though operative time did not significantly differ between the 2 groups, cardiopulmonary bypass time was significantly shorter in the LTHS group (61 vs 95 min, P CONCLUSIONS In this cohort, less invasive LVAD implantation appears to be associated with reduced postoperative RV failure, and equivalent or improved survival compared to conventional LVAD implantation.

Objective Several centers have presented minimally invasive surgical approaches to centrifugal left ventricular assist device implantation. Although minimally invasive implantation has been successfully performed by experienced surgeons, at large implanting centers, it is unknown whether these techniques are widely adoptable. We evaluated the experience of a surgeon early in his career with conventional and minimally invasive approaches to device implantation. Methods All consecutive left ventricular assist device implantations by a single surgeon in the first year of practice (2015–2016) were retrospectively reviewed. Patients were stratified by standard approach, conventional full sternotomy versus a minimally invasive approach, left anterior thoracotomy and upper hemisternotomy. Demographics, perioperative variables, and short-term outcomes were compared using Wilcoxon rank-sum test. Results Thirteen patients were identified: six performed via the standard approach and seven performed via the minimally invasive approach. Preoperative demographics were comparable in both groups. However, there was significantly more preoperative right ventricle dysfunction in the minimally invasive group ( P = 0.01). Although operative time was significantly longer in the minimally invasive cohort, there was a trend toward decreased cardiopulmonary bypass time. Six-month survival in both groups was 100%. Conclusions Compared with conventional sternotomy, minimally invasive ventricular assist device implantation, performed by a surgeon in his first year of practice, had similar perioperative outcomes and excellent survival. Based on these data, minimally invasive implantation may be a feasible strategy for device implantation even early in a surgeon's career.

Non-surgical bleeding (NSB) in heart failure (HF) patients with continuous-flow left ventricular assist device (CF-LVAD) support is the most common clinical complication. The aim of this study was to investigate the association between oxidative stress and platelet glycoproteins GPIbα and GPVI shedding on the incidence of NSB in CF-LVAD patients. Fifty-one HF patients undergoing CF-LVAD implantation and 11 healthy volunteers were recruited. Fourteen patients developed NSB (bleeder group) during one month follow-up duration while others were considered non-bleeder group (n=37). Several biomarkers of oxidative stress were quantified at baseline and weekly intervals in all patients. Surface expression and plasma elements of platelet receptor glycoproteins GPIbα and GPVI were measured. Oxidative stress biomarkers and platelet GPIbα and GPVI receptor-shedding (decreased surface expression and higher plasma levels) were found to be pre-existing conditions in baseline samples of both groups of HF patients when compared to healthy volunteers. Significantly elevated oxidative stress biomarkers and platelet-glycoprotein-receptor-shedding were observed in post implant bleeder group temporarily when compared to non-bleeder group. Strong significant associations between biomarkers of oxidative stress and platelet-glycoprotein-receptor-shedding were observed, suggesting a possible role of oxidative stress in platelet integrin shedding leading to NSB in CF-LVAD patients. Receiver operating characteristic (ROC) analyses of GPIbα and GPVI indicated that the likelihood of NSB had a predictive power of bleeding complication in CF-LVAD patients. In conclusion, elevated oxidative stress may play a role in GPIbα and GPVI shedding in the event of NSB. Thus, oxidative stress and GPIbα and GPVI shedding may be used as potential biomarkers for bleeding risk stratification in those patients.

Purpose Prior reports on minimally invasive LVAD insertion have focused on smaller and/or highly selected populations. Since 2016 we have used the lateral thoracotomy-hemisternotomy (LTHS) technique and the Heartware HVAD as our default approach for all patients. We compare these outcomes to our results with conventional sternotomy (CS). Methods Since April 2016, 58/61 HVAD patients (representing 61/62 total LVAD insertions) underwent LTHS. Two patients had CS due to stem-cell trial restrictions; one had a posterolateral thoracotomy due to hostile sternum . Outcomes of 60 LTHS procedures were compared to 52 CS dating to 2011. Results Preoperative characteristics (Table 1) were similar except for more males in the LTHS group. No patient was excluded from LTHS due to low Intermacs profile, presence of PFO/ASD, or high RV failure risk. Postoperative outcomes are shown in Table 2. Operative time was longer for LTHS. However, cardiopulmonary bypass (CPB) time, RVAD use, intraoperative red blood cell (RBC) transfusion ≥4U, reoperation for bleeding, operative mortality , and hospital length of stay (LOS) were all lower. One-year Kaplan-Meier estimated survival was 90% LTHS vs 65% CS (p=0.003). Conclusion Improved perioperative and long-term outcomes were observed when employing LTHS as the default technique in a large group of unselected patients.

Purpose Exercise tolerance, measured by pVO 2 during cardiopulmonary exercise stress test (CPET), is impaired in patients with LVAD. After LVAD, the right heart is more sensitive to afterload. We hypothesize that high RV afterload during exercise is associated with lower pVO 2 . Methods At routine right heart catheterization (RHC), LVAD patients performed supine bicycle exercise to maximal effort. Hemodynamics and echocardiograms at rest and peak exercise were collected. The same patients underwent CPET on different days as part of routine post-operative monitoring. We used effective arterial elastance (Ea = systolic PAP/stroke volume) to measure RV afterload, as it incorporates both pulsatile and resistive loads. Results Between 11/17 and 9/18, 10 patients (median age 54 years) had RHC, 8 of them had CPET. Time between LVAD and RHC was 244 days (IQ 223-299) and between CPET and RHC was 55 days (IQ 35-126). Work achieved (Watts) during CPET and RHC correlated linearly (α=1.1, p=0.003, R²=0.60). Patients had low pVO 2 (13.2 L/kg/min, IQ 11-18) and high VEVCO 2 slope (34, IQ 32-43) despite normal filling pressures and cardiac output (CO) after LVAD. They had no chronotropic incompetence (reaching 89.5% of max predicted heart rate, IQ 66.4-95.4). Compared to resting state, at peak exercise, filling pressures, CO, RV stroke work index, and RV tissue Doppler (S’) increased. Notably, pVO 2 negatively correlated with Ea at peak exercise and the change in Ea from rest to stress, while VEVCO 2 slope had the inverse correlations (Figure). pVO 2 did not correlate with changes in PCWP, CO, or LVAD flow. Moderate-severe baseline RV dysfunction and mild-moderate TR are associated with worse pVO 2 and VEVCO 2 slope. Conclusion This pilot study is the first to suggest that poor baseline RV function and high RV afterload at peak exercise are associated with worse pVO 2 and VEVCO 2 slope in LVAD patients. The practice of increasing pump speed may not be adequate to improve exercise tolerance and may be harmful to RV function.

Purpose We assessed the influence of preoperative cardiac anatomy and surgical approach on inflow cannula position in Heartware HVAD recipients. Methods We reviewed pre- and postoperative CT scans and echocardiography. Anatomic variables were chosen based on prior studies: LV end-diastolic dimension (LVEDD), axial plane midline-to-apex distance (ApexDist), and coronal-plane LV outflow tract angulation from horizontal (LVOT angle). Surgical technique was conventional sternotomy (CS) or lateral thoracotomy/hemisternotomy (LTHS). Inflow cannula angular deviation from a line intersecting the apex and mitral orifice center was measured in two planes. Anterior plane deviation is toward the superior or inferior free wall. Lateral plane deviation is toward the septum or lateral wall. Total deviation is the sum of the two. Cutoffs for malposition were deviation ≥ 20 deg in any direction or ≥ 40 deg total. Results 99 HVAD patients (43 CS, 56 LTHS) implanted since 2011 with pre- and postoperative CT were included. LVEDD was larger for LTHS (7.2 vs 6.7 cm, p=0.01). ApexDist and LVOT angle were similar between CS and LTHS. Figure shows inflow position by surgical technique. Inferior-wall deviation was common, while no patient had superior wall-directed malposition. Significantly more septal malposition occurred in CS patients (14% vs 2%; p=0.04). Shorter ApexDist predicted lateral wall malposition (p Conclusion Preoperative CT measurements and surgical approach were associated with different morphologies of HVAD inflow malposition. Surgical planning techniques to optimize inflow position are under study.

The role of oxidative stress and leukocyte activation has not been elucidated in developing systemic inflammatory response syndrome (SIRS) in heart failure (HF) patients after continuous-flow left ventricular assist device (CF-LVAD) implantation. The objective of this study was to investigate the change of plasma redox status and leukocyte activation in CF-LVAD implanted HF patients with or without SIRS. We recruited 31 CF-LVAD implanted HF patients (16 SIRS and 15 non-SIRS) and 11 healthy volunteers as the control. Pre- and postimplant blood samples were collected from the HF patients. Plasma levels of oxidized low-density lipoprotein (oxLDL), malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD) in erythrocyte, myeloperoxidase (MPO), and polymorphonuclear elastase (PMN-elastase) were measured. The HF patients had a preexisting condition of oxidative stress than healthy controls as evident from the higher oxLDL and MDA levels as well as depleted SOD and TAC. Leukocyte activation in terms of higher plasma MPO and PMN-elastase was also prominent in HF patients than controls. Persistent oxidative stress and reduced antioxidant status were found to be more belligerent in HF patients with SIRS after the implantation of CF-LVAD when compared with non-SIRS patients. Similar to oxidative stress, the activation of blood leukocyte was significantly highlighted in SIRS patients after implantation compared with non-SIRS. We identified that the plasma redox status and leukocyte activation became more prominent in CF-LVAD implanted HF patients who developed SIRS. Our findings suggest that plasma biomarkers of oxidative stress and leukocyte activation may be associated with the development of SIRS after CF-LVAD implant surgery.

We previously investigated preoperative variables associated with qualitative inflow cannula malposition in the HeartMate II (Thoratec-Abbott, Abbott Park, IL) continuous-flow left ventricular assist device. In this report, we assess inflow cannula malposition quantitatively in recipients of both the HeartMate II and the HeartWare (Medtronic-HeartWare, Minneapolis, MN) and examine its association with device thrombosis.Malposition was quantified based on angular deviation from a hypothetic ideal inflow cannula position in two orthogonal computed tomography imaging planes. Ideal position lies on a line from the apex to the center of the mitral valve. Positive anterior plane angulation indicates deviation toward the superior free wall; negative, toward the inferior wall. Positive lateral plane angulation indicates deviation toward the septum; negative, toward the lateral wall. Device thrombosis was assessed based on clinical criteria.Fifty-four HeartMate II patients and 68 HeartWare patients were analyzed. Inflow cannula deviation was significantly higher for HeartMate II than for HeartWare (anterior plane angle 36.7 ± 16.8 versus -18.7 ± 11.6 degrees, p0.001; lateral plane angle 23.7 ± 20.1 versus 0.2 ± 15.0 degrees, p0.001. Pump thrombosis occurred in 31% of HeartMate II patients and 2.9% of HeartWare patients (p0.001). In a multivariate model, HeartMate II and increasing inflow cannula deviation toward the septum were associated with higher thrombosis risk (odds ratio 1.35 per 10-degree increase).We found distinct device-dependent differences in inflow cannula positioning and thrombosis, with HeartWare showing both less malposition and less thrombosis. Malposition toward the ventricular septum may contribute to pump thrombosis through a vicious cycle of suction events, low flow, and speed reduction.

Introduction Oxidative stress and platelet integrin α2bβ3 plays important role in the process of hemostasis and thrombosis. We hypothesized that device-induced patient specific oxidative stress and integrin α2bβ3 shedding may be linked to major bleeding complication (MBC) in heart failure (HF) patients supported by continuous flow left ventricular assist devices (CF-LVADs). Materials and methods We recruited 47patients implanted with CF-LVADs and 15 healthy volunteers. Fourteen patients developed MBC (bleeder group) within one month after implantation while others were considered non-bleeder group (n = 33). Oxidative stresses were evaluated by measuring reactive oxygen species (ROS) in platelets, superoxide dismutase (SOD) activity, total antioxidant capacity (TAC) and oxidized low density lipoprotein (oxLDL). Assessments of α2bβ3 were carried out using flow cytometry and ELISA. Results Biomarkers of oxidative stress and α2bβ3 shedding (decreased surface expression and higher plasma levels) were found to be preexisting condition in all HF patients prior to CF-LVAD implantation compared to the healthy volunteers. Significantly elevated levels of ROS and oxLDL; concomitant depletion of SOD and TAC; and α2bβ3 shedding were observed in the bleeder group temporarily in comparison to the non-bleeder group after CF-LVAD implantation. A significantly strong association between α2bβ3 shedding and biomarkers of oxidative stress was observed; suggesting a potential role of oxidative stress in platelet integrin shedding leading to MBC after CF-LVAD implantation. Moreover, a receiver operating characteristic (ROC) analysis indicated that the likelihood of MBC data from Integrin α2bβ3 shedding had a predictive power of MBC in CF-LVAD patients. Conclusions Oxidative stress might play a potential role in accelerating α2bβ3 shedding and platelet dysfunction, resulting in MBC in CF-LVAD patients. Integrin α2bβ3 shedding may be used to refine bleeding risk stratification in CF-LVAD patients.

In this study, the Integrated Data Collection Analysis (IDCA) program has conducted a proficiency test for small-scale safety and thermal (SSST) testing of homemade explosives (HMEs). Described here are statistical analyses of the results from this test for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of the RDX Class 5 Type II standard. The material was tested as a well-characterized standard several times during the proficiency test to assess differences among participants and the range of results that may arise for well-behaved explosive materials.

One of the first steps in establishing safe handling procedures for explosives is small-scale safety and thermal (SSST) testing. To better understand the response of homemade or improvised explosives (HMEs) to SSST testing, 16 HME materials were compared to three standard military explosives in a proficiency-type round robin study among five laboratories, two U.S. Department of Defense and three U.S. Department of Energy, sponsored by the Department of Homeland Security, Science & Technology Directorate, Explosives Division. The testing included impact, friction, electrostatic discharge (ESD) and thermal. The testing matrix was designed to address problems encountered with improvised materials: powder mixtures, liquid suspensions, partially wetted solids, immiscible liquids, and reactive materials. All testing materials and/or precursors came from the same batch distributed to each of the participants and were handled, pretreated, and mixed by standardized procedures. For this proficiency test, the participants had similar equipment, usually differing by vintage. This allowed for a direct comparison of the results from each participant to the average of the results from all the participants. Some general trends observed for each series of tests were: (1) Drop hammer – LLNL usually found the materials less sensitive than the average with materials that have high sensitivity to impact and LANL usually found the materials less sensitive than the average with materials that have high sensitivity to impact; (2) friction – LLNL found the materials less sensitive than the average; (3) and ESD – IHD usually found the materials less sensitive than the average. In this report, the proficiency test data from all the participants is compared and contrasted for impact, selected friction, and ESD testing. Other friction and thermal data will be addressed elsewhere as well as the statistical analysis of several repeated measurements on the proficiency test standards.

Background Non-surgical bleeding (NSB) is a major complication among heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). Understanding the hemostatic defects contributing to NSB after CF-LVAD implantation is crucial for prevention of this adverse event. The aim of this study was to examine the link between platelet glycoprotein Ibα (GPIbα) ectodomain shedding and NSB in CF-LVAD recipients and to identify a potential biomarker of NSB. Methods Serial blood samples were collected from 35 HF patients supported with CF-LVADs. Platelet function was evaluated by a platelet function analysis device and thromboelastography (TEG). Platelet GPIbα shedding, von Willebrand factor (vWF) antigen and vWF collagen binding capacity were determined using enzyme-linked immunosorbent assays (ELISAs). The structural analysis of vWF was performed by gel electrophoresis. These platelet function measures with vWF parameters of the patients who had NSB between 4 and 32 days after CF-LVAD implantation (bleeder) were analyzed against those without NSB (non-bleeder). Blood samples from 7 healthy individuals were collected to obtain healthy reference values for the laboratory assays. Results Elevated GPIbα shedding was found to be a pre-existing condition in all HF patients prior to CF-LVAD implantation. Post-operative level of GPIbα shedding increased and remained elevated in the bleeder group, whereas a consistent decrease was found in the non-bleeder group. A receiver operating characteristic (ROC) analysis indicated that the level of GPIbα shedding had a predictive power of NSB in patients on CF-LVAD support. Conclusions Platelet GPIbα ectodomain shedding which attenuates platelet reactivity is associated with NSB. Plasma GPIbα level may potentially be used to refine bleeding risk stratification in CF-LVAD patients.

Purpose We evaluated the effect of different inflow cannula malposition morphologies on readmission and selected complication rates in Heartware HVAD recipients. Methods Inflow malposition was defined as the angular deviation from a line intersecting the apex and mitral orifice center in two CT imaging planes. Anterior plane deviation is toward the superior or inferior free wall. Lateral plane deviation is toward the septum or lateral wall. Total deviation is the sum of the two. Cutoffs for malposition were deviation ≥ 20 deg in any direction and total deviation ≥ 40 deg. Clinical outcomes were: 30-day and total cardiovascular-related readmissions (CVR; excludes bleeding, infections, noncardiac procedures, transplants); persistent VT/VF (pVT; ≥ 2 episodes); combined pump thrombosis (PT) or embolic stroke (PT-eCVA); and 90-day mortality. Results 99 HVAD patients implanted since 2011 with postoperative CT scans were included. All were followed for complications. 87 were discharged and were assessed for CVR. Prevalence of each morphology of malposition is shown in Table. Deviation toward the inferior free wall occurred most frequently. Eighteen of 87 patients (21%) had 30-day CVR. Total deviation ≥ 40 deg was significantly associated with 30-day CVR (p=0.01). Median total CVR rate was 0.21/100 pt-days (IQR 0-0.68). Inferior wall deviation ≥ 20 deg was significantly associated with total CVR rate (p = 0.03). Eight of 99 patients (8.1%) had PT-eCVA (5 eCVA, 3 PT), 27% had pVT, and 90-day mortality occurred in 7%. No malposition measurement predicted any of these complications. Conclusion PT-eCVA, pVT, and early mortality were not associated with malposition. However, worse overall malposition was associated with 30-day CVR. Inferior wall malposition occurred in half of patients and was associated with overall CVR rate. Improved surgical planning techniques to mitigate malposition are warranted.

1. Lund LH, Matthews J, Aaronson K. Patient selection for left ventricular assist devices. Eur J Heart Fail 2010;12:516-20. 2. Mancini D, Lietz K. Selection of cardiac transplantation candidates in 2010. Circulation 2010;122:173-83. 3. Kirklin JK, Naftel DC, Kormos RL, et al. The fourth INTERMACS annual report: 4,000 implants and counting. J Heart Lung Transplant 2012;31:117-26. 4. Miller LW. Left ventricular assist devices are underutilized. Circulation 2011;123:1552-8: discussion 1558. 5. Massad MG. Current trends in heart transplantation. Cardiology 2004;101:79-92. 6. McAlister FA, Ezekowitz J, Hooton N, et al. Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review. JAMA 2007;297:2502-14. 7. Goda A, Williams P, Mancini D, Lund LH. Selecting patients for heart transplantation: comparison of the Heart Failure Survival Score (HFSS) and the Seattle Heart Failure Model (SHFM). J Heart Lung Transplant 2011;30:1236-43. 8. Mehra MR, Kobashigawa J, Starling R, et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006. J Heart Lung Transplant 2006;25:1024-42. 9. Stehlik J, Edwards LB, Kucheryavaya AY, et al. The registry of the International Society for Heart and Lung Transplantation: 29th official adult heart transplant report—2012. J Heart Lung Transplant 2012;31:1052-64.

Institutional Affiliations Co-chairs Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, Georgia Institute of Technology and Morehouse School of Medicine; Pamboukian SV: University of Alabama at Birmingham, Birmingham, Alabama; Teuteberg JJ: University of Pittsburgh, Pittsburgh, Pennsylvania Task force chairs Birks E: University of Louisville, Louisville, Kentucky; Lietz K: Loyola University, Chicago, Maywood, Illinois; Moore SA: Massachusetts General Hospital, Boston, Massachusetts; Morgan JA: Henry Ford Hospital, Detroit, Michigan Contributing writers Arabia F: Mayo Clinic Arizona, Phoenix, Arizona; Bauman ME: University of Alberta, Alberta, Canada; Buchholz HW: University of Alberta, Stollery Children’s Hospital and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada; Deng M: University of California at Los Angeles, Los Angeles, California; Dickstein ML: Columbia University, New York, New York; El-Banayosy A: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Elliot T: Inova Fairfax, Falls Church, Virginia; Goldstein DJ: Montefiore Medical Center, New York, New York; Grady KL: Northwestern University, Chicago, Illinois; Jones K: Alfred Hospital, Melbourne, Australia; Hryniewicz K: Minneapolis Heart Institute, Minneapolis, Minnesota; John R: University of Minnesota, Minneapolis, Minnesota; Kaan A: St. Paul’s Hospital, Vancouver, British Columbia, Canada; Kusne S: Mayo Clinic Arizona, Phoenix, Arizona; Loebe M: Methodist Hospital, Houston, Texas; Massicotte P: University of Alberta, Stollery Children’s Hospital, Edmonton, Alberta, Canada; Moazami N: Minneapolis Heart Institute, Minneapolis, Minnesota; Mohacsi P: University Hospital, Bern, Switzerland; Mooney M: Sentara Norfolk, Virginia Beach, Virginia; Nelson T: Mayo Clinic Arizona, Phoenix, Arizona; Pagani F: University of Michigan, Ann Arbor, Michigan; Perry W: Integris Baptist Health Care, Oklahoma City, Oklahoma; Potapov EV: Deutsches Herzzentrum Berlin, Berlin, Germany; Rame JE: University of Pennsylvania, Philadelphia, Pennsylvania; Russell SD: Johns Hopkins, Baltimore, Maryland; Sorensen EN: University of Maryland, Baltimore, Maryland; Sun B: Minneapolis Heart Institute, Minneapolis, Minnesota; Strueber M: Hannover Medical School, Hanover, Germany Independent reviewers Mangi AA: Yale University School of Medicine, New Haven, Connecticut; Petty MG: University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota; Rogers J: Duke University Medical Center, Durham, North Carolina

Objective: To study the status of oxidative stress and DNA damage repair in circulating blood leukocytes of heart failure patients supported by continuous flow left ventricular assist devices (LVADs). Materials and methods: Ten HF patients implanted with LVAD as bridge to transplant or destination therapy were enrolled in the study and 10 age and sex matched volunteers were recruited as the study control. Reactive oxygen species (ROS) in blood leukocytes and superoxide dismutase (SOD) in erythrocytes were measured by flow cytometry/immunofluorescence microscopy and spectrophotometry, respectively. ELISA was used to measure oxidized low density lipoproteins (oxLDL) in plasma. Markers of DNA damage (γ-H2AX) and repairs (Mre11, DNA ligase IV, Ku70, and Ku80) were quantified in blood lymphocytes by immunocytochemistry. Results: Levels of ROS and oxLDL were significantly higher in HF patients with LVAD than baseline as well as the control group; moreover, SOD levels were decreased with increasing post-operative periods. All the changes indicated enhanced oxidative stress among LVAD recipients. Significantly higher γ-H2AX foci in lymphocytes confirmed DNA double strand breaks in LVAD recipients. γ-H2AX foci numbers in lymphocytes were positively correlated with the ROS and oxLDL and negatively with SOD levels (p