Binding of Dissolved Organic Matter to RNA and Protection from Nuclease-Mediated Degradation.

The persistence of RNA in environmental systems is an important parameter for emerging applications, including ecological surveys, wastewater-based epidemiology, and RNA interference biopesticides. RNA persistence is controlled by its rate of biodegradation, particularly by extracellular enzymes, although the specific factors determining this rate have not been characterized. Due to prior work suggesting that nucleic acids-specifically DNA-interact with dissolved organic matter (DOM), we hypothesized that DOM may bind RNA and impede its biodegradation in natural systems. We first adapted a technique previously used to assess RNA-protein binding to differentiate RNA that is bound at all sites by DOM from RNA that is unbound or partially bound by DOM. Results from this technique suggested that humic acids bound RNA more extensively than fulvic acids. At concentrations of 8-10 mgC/L, humic acids were also found to be more effective than fulvic acids at suppressing enzymatic degradation of RNA. In surface water and soil extract containing DOM, RNA degradation was suppressed by 39-46% relative to pH-adjusted controls. Due to the ability of DOM to both bind and suppress the enzymatic degradation of RNA, RNA biodegradation may be slowed in environmental systems with high DOM concentrations, which may increase its persistence.

RNA Hydrolysis at Mineral-Water Interfaces.

As an essential biomolecule for life, RNA is ubiquitous across environmental systems where it plays a central role in biogeochemical processes and emerging technologies. The persistence of RNA in soils and sediments is thought to be limited by enzymatic or microbial degradation, which occurs on timescales that are orders of magnitude faster than known abiotic pathways. Herein, we unveil a previously unreported abiotic pathway by which RNA rapidly hydrolyzes on the timescale of hours upon adsorption to iron (oxyhydr)oxide minerals such as goethite (α-FeOOH). The hydrolysis products were consistent with iron present in the minerals acting as a Lewis acid to accelerate sequence-independent hydrolysis of phosphodiester bonds comprising the RNA backbone. In contrast to acid- or base-catalyzed RNA hydrolysis in solution, mineral-catalyzed hydrolysis was fastest at circumneutral pH, which allowed for both sufficient RNA adsorption and hydroxide concentration. In addition to goethite, we observed that RNA hydrolysis was also catalyzed by hematite (α-Fe2O3) but not by aluminum-containing minerals (e.g., montmorillonite). Given the extensive adsorption of nucleic acids to environmental surfaces, we anticipate previously overlooked mineral-catalyzed hydrolysis of RNA may be prevalent particularly in iron-rich soils and sediments, which must be considered across biogeochemical applications of nucleic acid analysis in environmental systems.

Amine Volatilization from Herbicide Salts: Implications for Herbicide Formulations and Atmospheric Chemistry.

Amines are frequently included in formulations of the herbicides glyphosate, 2,4-D, and dicamba to increase herbicide solubility and reduce herbicide volatilization by producing herbicide-amine salts. Amines, which typically have higher vapor pressures than the corresponding herbicides, could potentially volatilize from these salts and enter the atmosphere, where they may impact atmospheric chemistry, human health, and climate. Amine volatilization from herbicide-amine salts may additionally contribute to volatilization of dicamba and 2,4-D. In this study, we established that amines applied in herbicide-amine salt formulations undergo extensive volatilization. Both dimethylamine and isopropylamine volatilized when aqueous salt solutions were dried to a residue at ∼20 °C, while lower-vapor pressure amines like diglycolamine and n,n-bis-(3-aminopropyl)methylamine did not. However, all four amines volatilized from salt residues at 40-80 °C. Because amine loss typically exceeded herbicide loss, we proposed that neutral amines dominated volatilization and that higher temperatures altered their protonation state and vapor pressure. Due to an estimated 4.0 Gg N/yr applied as amines to major U.S. crops, amine emissions from herbicide-amine salts may be important on regional scales. Further characterization of worldwide herbicide-amine use would enable this contribution to be compared to the 285 Gg N/yr of methylamines emitted globally.

Metal-Catalyzed Hydrolysis of RNA in Aqueous Environments.

The stability of RNA in aqueous systems is critical for multiple environmental applications including evaluating the environmental fate of RNA interference pesticides and interpreting viral genetic marker abundance for wastewater-based epidemiology. In addition to biological processes, abiotic reactions may also contribute to RNA loss. In particular, some metals are known to dramatically accelerate rates of RNA hydrolysis under certain conditions (i.e., 37 °C or higher temperatures, 0.15-100 mM metal concentrations). In this study, we investigated the extent to which metals catalyze RNA hydrolysis under environmentally relevant conditions. At ambient temperature, neutral pH, and ∼10 µM metal concentrations, we determined that metals that are stronger Lewis acids (i.e., lead, copper) catalyzed single-stranded (ss)RNA, whereas metals that are weaker Lewis acids (i.e., zinc, nickel) did not. In contrast, double-stranded (ds)RNA resisted hydrolysis by all metals. While lead and copper catalyzed ssRNA hydrolysis at ambient temperature and neutral pH values, other factors such as lowering the solution pH and including inorganic and organic ligands reduced the rates of these reactions. Considering these factors along with sub-micromolar metal concentrations typical of environmental systems, we determined that both ssRNA and dsRNA are unlikely to undergo significant metal-catalyzed hydrolysis in most environmental aqueous systems.

Dealing with different conceptions of pollution in the Gene Regulation Knowledge Commons.

Current research of gene regulatory mechanisms is increasingly dependent on the availability of high-quality information from manually curated databases. Biocurators undertake the task of extracting knowledge claims from scholarly publications, organizing these claims in a meaningful format and making them computable. In doing so, they enhance the value of existing scientific knowledge by making it accessible to the users of their databases. In this capacity, biocurators are well positioned to identify and weed out information that is of insufficient quality. The criteria that define information quality are typically outlined in curation guidelines developed by biocurators. These guidelines have been prudently developed to reflect the needs of the user community the database caters to. The guidelines depict the standard evidence that this community recognizes as sufficient justification for trustworthy data. Additionally, these guidelines determine the process by which data should be organized and maintained to be valuable to users. Following these guidelines, biocurators assess the quality, reliability, and validity of the information they encounter. In this article we explore to what extent different use cases agree with the inclusion criteria that define positive and negative data, implemented by the database. What are the drawbacks to users who have queries that would be well served by results that fall just short of the criteria used by a database? Finally, how can databases (and biocurators) accommodate the needs of such more explorative use cases?

Mid-term Outcome of the Edge-To-Edge Mitral Valve Repair Via Aortic Outflow Tract in High-Risk Patients.

The edge-to-edge mitral valve repair technique, invented by Alfieri and colleagues, introduced valve repair as a treatment option for patients with complex diseases where standard annuloplasty and related repair techniques are insufficient, due to annular calcification and patient frailty. We retrospectively evaluated the results of a transaortic edge-to-edge mitral valve repair (Alfieri stitch) in high-risk patients who were undergoing aortic valve replacement. From February, 2012 to December, 2017, 43 patients underwent transaortic edge-to-edge mitral valve repair with concomitant aortic valve replacement at a single institution. Preoperative and postoperative echocardiograms were compared. Home telephone follow up was conducted and postoperative morbidity was examined, including the need for reoperation, stroke and cardiac arrhythmia. 30-day and long-term survival rates were also determined. Mitral regurgitation (MR) was graded semi-quantitatively as 0 (trace and/or none), mild (1), moderate (2) or moderate to severe (3-4). The patients were 74 ± 7.8 years old. 65% of the patients were male. Mean cardiopulmonary bypass time was 115 ± 37 minutes and mean cross-clamp time was 71 ± 23 minutes. There was a significant improvement in preoperative vs postoperative median MR grade (2 (IQR 2-3) vs 0 (IQR 0-1); P = 0.05). Follow-up transthoracic echocardiograms in 29 patients obtained at a median of 9 months' (range 3 - 19 months') and in 16 patients at a median of 34 months' postoperatively (range 21 - 53 months') showed mild (1 (IQR 1-2)) grade of mitral regurgitation. 30-day survival was 98%. Long term survival at 12 and 24 months' were 88% and 81% respectively. Mitral valve reoperation was conducted in 1 patient (2%), who was suffering of endocarditis. Stroke occurred in 2 patients (7%). Cardiac arrhythmia was observed in 15 patients (35%). 8 patients (19%) suffered from atrial fibrillation and 7 patients (16%) displayed atrioventricular blockage. 10 patients (23%) could be treated conservatively and 5 patients (12%) needed implantation of a pacemaker. Transaortic edge-to-edge mitral valve repair can be safely performed during aortic valve replacement in high-risk patients and improves even long-term MR grade. Postoperative cardiac arrhythmia occurs frequently. 66% of them could be treated successfully by conservative procedures.

Duplex Structure of Double-Stranded RNA Provides Stability against Hydrolysis Relative to Single-Stranded RNA.

Phosphodiester bonds in the backbones of double-stranded (ds)RNA and single-stranded (ss)RNA are known to undergo alkaline hydrolysis. Consequently, dsRNA agents used in emerging RNA interference (RNAi) products have been assumed to exhibit low chemical persistence in solutions. However, the impact of the duplex structure of dsRNA on alkaline hydrolysis has not yet been evaluated. In this study, we demonstrated that dsRNA undergoes orders-of-magnitude slower alkaline hydrolysis than ssRNA. Furthermore, we observed that dsRNA remains intact for multiple months at neutral pH, challenging the assumption that dsRNA is chemically unstable. In systems enabling both enzymatic degradation and alkaline hydrolysis of dsRNA, we found that increasing pH effectively attenuated enzymatic degradation without inducing alkaline hydrolysis that was observed for ssRNA. Overall, our findings demonstrated, for the first time, that key degradation pathways of dsRNA significantly differ from those of ssRNA. Consideration of the unique properties of dsRNA will enable greater control of dsRNA stability during the application of emerging RNAi technology and more accurate assessment of its fate in environmental and biological systems, as well as provide insights into broader application areas including dsRNA isolation, detection and inactivation of dsRNA viruses, and prebiotic molecular evolution.

Lateral Thoracotomy for Ventricular Assist Device Implantation: A Meta-Analysis of Literature.

The use of lateral thoracotomy (LT) for implanting left ventricular assist devices (LVADs) is worldwide increasing, although the available evidence for its positive effects compared with conventional sternotomy (CS) is limited. This systematic review and meta-analysis analyzes the outcomes of LT compared with CS in patients undergoing implantation of a centrifugal continuous-flow LVAD. Four databases and 1,053 publications were screened until December 2019. Articles including patients undergoing implantation of a centrifugal continuous-flow LVAD through LT were included. A meta-analysis to compare LT and CS was performed to summarize evidences from studies including both LT and CS patients extracted from the same population. Primary outcome measure was in-hospital or 30-day mortality. Eight studies reporting on 730 patients undergoing LVAD implantation through LT (n = 242) or CS (n = 488) were included in the meta-analysis. Left thoracotomy showed lower in-hospital/30-day mortality (odds ratio [OR]: 0.520, 95% confidence interval [CI]: 0.27-0.99, p = 0.050), shorter intensive care unit (ICU) stay (mean difference [MD]: 3.29, CI: 1.76-4.82, p < 0.001), lower incidence of severe right heart failure (OR: 0.41; CI: 0.19-0.87, p = 0.020) and postoperative right ventricular assist device (RVAD) implantation (OR: 0.27, CI: 0.10-0.76, p = 0.010), fewer perioperative transfusions (MD: 0.75, CI: 0.36-1.14, p < 0.001), and lower incidence of renal failure (OR: 0.45, CI: 0.20-1.01, p = 0.050) and device-related infections (OR: 0.45, CI: 0.20-1.01, p = 0.050), respectively. This meta-analysis demonstrates that implantation of a centrifugal continuous-flow LVAD system via LT benefits from higher short-term survival, less right heart failure, lower postoperative RVAD need, shorter ICU stay, less transfusions, lower risk of device-related infections and kidney failure. Prospective studies are needed for further proof.

Flying after left ventricular assist device implantation.

Literature on the air travel activities of patients supported by permanent mechanical assist devices is rare. To the best of our knowledge, no air travel guidelines or fitness prerequisites exist on whether and when ventricular assist device (VAD) patients are allowed to travel by plane after device implantation. In this study, we evaluated the topic of air travel after VAD implantation. This working group aimed to produce a report on air travel passengers supported by VADs, regarding their fitness to fly. Fifty left ventricular assist device (LVAD) patients were surveyed in a worldwide multicenter study. The single survey was performed with a multimethod design, including interviews conducted face-to-face, online, and on phone. Out of 50 patients, 97% described their traveling by aircraft as perfect and uneventful during the flight. Eighty-five percent of the study participants consulted their medical practitioner before the flight. No patient reported the occurrence of a severe condition associated with flying. LVAD alarms, especially low flow alarms, did not occur in any of the devices. Thirty-five percent of the surveyed patients, however, stated a major problem pertaining to the security check procedures at the airport. The results of this study suggest that commercial air travel is safe for stable patients on permanent VAD support and traveling can be resumed securely after VAD implantation. Conscientious preparation by packing necessary devices, fluids, medications, and careful preparation for the airport security check is recommended.

Minimally invasive left ventricular assist device implantation: optimizing device design for this approach.

Introduction: The global heart failure (HF) burden is expected to increase due to aging populations, increasing number of end-stage HF patients and adverse lifestyle changes. Mechanical circulatory support (MCS) devices such as left ventricular assist devices (LVADs) have become a promising treatment option for short-term and long-term circulatory support of end-stage HF patients.Areas covered: Recent developments in MCS technology have been focused on miniaturization leading to the development of minimally invasive surgical procedures for LVAD implantation. This helps overcome possible postoperative complications such as major incisions and poor outcomes due to infections, right heart failure, and bleeding. This article discusses clinical and technological developments in the field of minimally invasive procedures for LVAD implantation.Expert opinion: Most patients might benefit from minimally invasive LVAD implantation performed through a limited left lateral thoracotomy associated with an upper hemisternotomy or a right anterior thoracotomy. The thoracotomy approach can also be considered in case of pump exchange or pump explant. The success of these techniques is mainly based on the optimization of LVAD pump design, inflow cannula insertion, and outflow graft as well as driveline exit sites. The future direction of the LVAD field is likely to include less-invasive approaches and smartificial technologies.

Bioconversion of renewable feedstocks by Rhodococcus opacus.

The production of fuels and chemicals from renewable feedstocks is necessary for a fossil fuel independent economy. Lignin and other industrial wastes represent sustainable, non-food feedstocks that can be tapped for microbe-based bioproduction. Rhodococcus opacus is a gram-positive bacterium capable of catabolizing a broad range of feedstocks, and recent technological advances have further established its potential for lignin and industrial waste valorization. In the process of developing R. opacus as a platform for bioproduction, metabolic profiling has elucidated its native mechanisms of bioconversion, adaptive evolution has enhanced its tolerance towards inhibitory feedstocks, and genetic engineering has enabled it to produce novel products, such as wax esters, free fatty acids, and long chain hydrocarbons. Here, we present recent examples of broad feedstock utilization and value-added chemical production by R. opacus, demonstrating its potential as an industrially relevant strain.

Device profile of the heartware HVAD system as a bridge-to-transplantation in patients with advanced heart failure: overview of its safety and efficacy.

Introduction: Heart failure (HF) is one of the rising problems in the contemporary society with growing incidences of end-stage HF. While heart transplantation (HT) is the gold standard treatment for end-stage HF, its availability is limited by the lack of heart donors. As a consequence, left ventricular assist devices (LVADs) are becoming key therapies as bridge to transplant (BTT) strategy to improve survival and outcomes.Areas covered: A significant advancement for wider applications of LVADs as BTT was facilitated by the introduction of miniaturized pumps such as the HVAD (HeartWare®, Medtronic, MN, USA), allowing intrapericardial implants and less-invasive approaches. In this review article, we describe the technical features of the HVAD and its outcomes in terms of efficacy and safety when implanted as BTT strategy. Moreover, we discuss the postoperative results of HT in HVAD recipients and its application in the pediatric population.Expert opinion: It has been demonstrated that the HVAD positively influences the survival of end-stage HF patients awaiting HT, with an acceptable rate of adverse events. Due to its reduced size, it is particularly suitable for LVAD implantations through lateral thoracotomy and in patients with small thoracic dimensions.

Initial experience with telemonitoring in left ventricular assist device patients.

BACKGROUND: Left ventricular assist devices (LVAD) are increasingly used in patients with end stage heart failure. The HeartAssist 5 and aVAD LVADs offer telemetric monitoring capabilities. Here we report our initial single centre experience with the largest telemonitoring cohort of LVAD patients. METHODS: Eleven patients (9 males) received a telemonitoring-capable LVAD and were included in our telemonitoring cohort. Waveforms and alarm data were obtained from the telemonitoring system and hospital records were reviewed for clinical data. RESULTS: Mean age at LVAD implantation was 59±5.1 years (mean ± standard deviation). Seven patients had non-ischemic cardiomyopathy and 4 patients had ischemic cardiomyopathy. Median LVEF at implant was 16% (IQR, 15-20%). The total follow-up time was 2,438 patient-days. A total of 6,216 alarm messages were generated in 11 patients. Most common were low flow alarms due to hypovolemia, followed by low flow alarms because of suspected pump thrombosis. One patient died during follow-up, one received a cardiac transplant and one had the LVAD explanted because of pump thrombosis. Pump thrombosis was suspected in 5 patients with 8 episodes of sudden flow decreases and laboratory signs of haemolysis. CONCLUSIONS: Real-time telemonitoring of LVAD pump flow, motor speed and power consumption is a promising tool in the follow-up of LVAD recipients. Trending pump flow over hours or days can assist in the early detection of complications, especially flow reductions due to hypovolemia and LVAD thrombosis. Further studies are warranted to delineate the impact of remote monitoring on patients' prognosis.

In vitro study for the evaluation of transluminal aspiration as a novel treatment option for thrombosis in the HeartWare HVAD.

INTRODUCTION:: Pump thrombosis of left ventricular assist devices remains a devastating complication with high morbidity and mortality. Despite the improvements made, the matter affects many patients and the treatment options are limited to thrombolysis and surgical replacement. An alternative approach using the aspiration Indigo catheter was tested. METHODS:: An Indigo thrombectomy catheter was used within an in vitro model to assess the direct aspiration of prefabricated clots from three different positions within the HeartWare HVAD (inlet, outlet, and housing). The experiments were conducted with a straight and an angled catheter. The aspiration pressure was constant. The flow, power consumption, and pressure head of the left ventricular assist devices were measured at pre-defined measuring points. RESULTS:: The device was more effective (success rate 71%) at inlet and outlet of the left ventricular assist device. In addition, the duration of aspiration and the aspiration volume were shorter in comparison to the aspiration in the housing (inlet M = 19.75 s, outlet M = 60.50 s, and housing M = 38.75 s). Moreover, the aspiration volume was associated with the aspiration duration and the weight of thrombi but not with their volume. Noteworthy, the angled catheter showed an improved performance compared to the straight one (67%-33%). The recorded parameters showed no major changes during the use of the catheter. After application of the Indigo catheter, flow and pressure head of the pump could be restored. CONCLUSIONS:: The aspiration system showed promising results under specific conditions for the treatment of pump thrombosis in an in vitro model. However, further examination, including in vivo experiments, will justify its effectiveness.

Minimally invasive surgery improves outcome of left ventricular assist device surgery in cardiogenic shock.

BACKGROUND: Left ventricular assist device (LVAD) (HVAD, Medtronic, Minneapolis, MN, USA) implantation is already a widely accepted treatment option for end-stage heart failure (HF) but also still considered as a rescue therapy for patients suffering from cardiogenic shock. Standard LVAD implantation techniques are often associated with high mortality rates and can result in severe complications, like bleeding or right heart failure (RHF). The aim of our study was to assess the outcome of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 1 patients (so called "crash and burn" patients) undergoing a LVAD implantation by standard or less invasive surgery. METHODS: We performed a retrospective evaluation of the 1-year outcome of 32 consecutive HF patients in cardiogenic shock, who underwent LVAD implantation in our institution. A total of 32 INTERMACS 1 patients were emergently operated. Fourteen patients (group A) were operated by using the "Hannover-VAD-technique", which is widely known to be less invasive (upper hemisternotomy and a left-sided anterolateral thoracotomy). In contrast, 18 patients (group B) were implanted with LVAD by using the standard technique (full sternotomy). The primary endpoint was survival after 1 year without device-related re-operations. Secondary endpoints included combined analyses of rates of RHF, respiratory failure and bleeding during the trial period. RESULTS: Baseline characteristics were similar in both groups. Survival after 1 year was higher in group A (69.7% vs. 50.0%). Technique-related adverse events (AEs) were also lower in the minimally invasive group, including a lower RHF (35.7% vs. 61.1%) and of further postoperative bleeding requiring surgery (14.3% vs. 33.3%). CONCLUSIONS: LVAD surgery in INTERMACS 1 patients is associated with remarkably good outcome considering the already very high mortality of those patients, and compared to previously reported surgical outcomes. Our study indicates that minimally invasive LVAD implantation in cardiogenic shock decreases mortality and the incidence of postoperative AEs.

Reduction of driveline infections through doubled driveline tunneling of left ventricular assist devices-5-year follow-up.

BACKGROUND: Driveline infection (DLI) is one of the leading causes for unplanned re-admissions of patients undergoing therapy with left ventricular assist devices (LVAD). In previous studies our group was able to show that a double tunneling implantation technique could significantly reduce infection rates one year after implantation. We now report the results of the five-year-follow up of patients receiving the double tunneling technique. METHODS: We retrospectively analyzed patients receiving LVAD therapy with the HeartWare ventricular assist device (HVAD) (Medtronic, Minnesota, MN, USA) LVAD. For 36 patients (group 1) the driveline was tunneled via a conventional technique. In the remaining 33 patients (group 2) the drivelines were implanted by means of a double tunneling technique. The double tunnel driveline technique involved placement of the driveline in the sheath of the rectus muscle in the umbilical direction and then subcutaneously to the left (alternatively right) upper quadrant. We retrospectively compared both groups. Primary outcome parameters were infection rate and mortality. RESULTS: Five years after LVAD implantation the DLI rate of patients operated by a double tunneling technique was significantly lower than in the conventional technique group [61% (n=22) group 1 vs. 30% (n=10) group 2, P=0.004]. The 5-year mortality was lower in group 2 [42% (n=15) group 1 vs. 27% (n=9) group 2] but did not achieve statistical significance (P=0.10). The days of LVAD support between the two groups were comparable (1,275.56±885.89 group 1 vs. 1,321.94±711.37 group 2). The tunnel technique itself showed to be strongly associated with the occurrence of DLI. Other elevated variables are liver disease and dilated cardiomyopathy as primary disease. CONCLUSIONS: Double tunneling technique for driveline implantation leads to significantly lowered infection rates after 5 years of LVAD therapy and it is associated with a lower mortality.

An acoustic method for systematic ventricular assist device thrombus evaluation with a novel artificial thrombus model.

BACKGROUND: Pump thrombosis (PT) is still one of the major adverse events in patients supported with left ventricular assist devices. Nowadays, thrombus detection relies on clinical parameters like reoccurring heart failure symptoms, on changes in pump power consumption, and on laboratory parameters such as increased LDH and hemolysis. Once detected PT is most often persistent and refractory to medical therapy. We therefore designed a novel, non-invasive acoustic method for early pump thrombus detection in an in vitro artificial thrombus model. METHODS: The study was performed in vitro using a mock circulation loop, artificial blood (water-glycerin) and artificial thrombus material (silicon) allowing for repeatable and defined testing. Tested ventricular assist device (VAD) type was HVAD (Medtronic). Three different thrombus locations were evaluated: on the tilted pad of the rotor, in the primary flow path, and in the secondary flow path beneath the rotor. After evaluating baseline parameters (no thrombus, n=20 for each pump), the influence of thrombi of seven different masses (no thrombus, 0.5-5.0 mg) on pump power consumption and acoustic emission of four HVAD devices was investigated via a microphone system (Sennheiser) and subsequent frequency spectrum analysis (n=12). The acoustic analysis algorithm included the number of frequency peaks recorded. RESULTS: Measurements with thrombi on the tilted pad showed an increased number of frequency peaks with all thrombus sizes compared to baseline measurements without any thrombus (baseline: 32.7±7.4; 0.5 mg: 45.3±10.4 up to 5 mg: 80.4±5.5). Power consumption was relevantly elevated in 5mg thrombus measurement only (6.3±1.29 W compared to 4.9±0.14 W at baseline). Measurements with thrombi in the primary and secondary showed no relevant alteration in power consumption and frequency peak count. CONCLUSIONS: We present an acoustic method that detects pump thrombi located on the tilted pad of the HVAD rotor requiring ten times less mass compared to thrombi detected by power consumption alterations used in current detection algorithms. Assuming that pump thrombi are growing over several days, the presented method may detect PT much earlier thereby increasing efficacy of medical therapy and helping to avoid pump exchange.

Left ventricular assist device exchange for the treatment of HeartMate II pump thrombosis.

BACKGROUND: Pump thrombosis is the most severe and acute complication of left ventricular assist device (LVAD) therapy and treatment remains challenging. Whilst lysis therapy is often not successful, the exchange of the occluded LVAD is currently the most applied therapeutic treatment for this event. With this study we examine the effects of minimal-invasive LVAD exchange on the rate re-thrombosis and outcomes as well as adverse events in the study group. METHODS: Between February 2004 and December 2015 more than 600 LVADs were implanted at our institution. We retrospectively studied a patient cohort of 41 patients who underwent LVAD exchange because of pump thrombosis at a single institution. Outcomes, rates of re-thrombosis and adverse events were analyzed. RESULTS: Between February 2004 and December 2015, 87 exchanges of LVADs were performed at a single center. In 41 cases pump thrombosis was the reason for LVAD exchange. A total of 28 patient years (10,276 days) were analyzed. Average ICU stay was 15.8±20.4 days and average in-hospital stay 38.1±37.3 days after LVAD exchange. After thirty days the survival rate was 80.5%, 75.6% after 6 months and 70.7% one year after LVAD exchange. Out of the study cohort, three patients have successfully undergone heart transplantation. Twelve patients suffered a stroke postoperatively (29%). Twelve patients needed postoperative dialysis (29%). No technical complications of the VAD were recorded in the study group. Two patients underwent successful LVAD explantation due to myocardial recovery. One year after LVAD exchange, 14 patients underwent re-exchange due to pump thrombosis (34%). Eight patients suffered from a LVAD related infection out of which two patients were treated by pump exchange. A total of 12 patients died during the complete one year follow up of this study (29%). Four patients died in the second, two in the third and one in the fourth year after LVAD exchange. The remaining 17 patients are still ongoing on the device.Conclusions: It is generally feasible to treat pump thrombosis via LVAD exchange. Yet, the exchange procedure is not without risk and the risk of re-thrombosis (34%), stroke (29%), postoperative dialysis (29%) and perioperative complications remains high.