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OBJECTIVES Bridging from a temporary microaxial left ventricular assist device (tLVAD) to a durable left ventricular assist device (dLVAD) is playing an increasing role in the treatment of terminally ill patients with heart failure. Scant data exist about the best implant strategy. The goal of this study was to analyse differences in the dLVAD implant technique and effects on patient outcomes. METHODS Data from 341 patients (19 European centres) who underwent a bridge-to-bridge implant from tLVAD to dLVAD between January 2017 and October 2022 were retrospectively analysed. The outcomes of the different implant techniques with the patient on cardiopulmonary bypass, extracorporeal life support or tLVAD were compared. RESULTS A durable LVAD implant was performed employing cardiopulmonary bypass in 70% of cases (n  = 238, group 1), extracorporeal life support in 11% (n  = 38, group 2) and tLVAD in 19% (n  = 65, group 3). Baseline characteristics showed no significant differences in age (P  = 0.140), body mass index (P  = 0.388), creatinine level (P  = 0.659), the Model for End-Stage Liver Disease (MELD) score (P  = 0.190) and rate of dialysis (P  = 0.110). Group 3 had significantly fewer patients with preoperatively invasive ventilation and cardiopulmonary resuscitation before the tLVAD was implanted (P  = 0.009 and P  < 0.001 respectively). Concomitant procedures were performed more often in groups 1 and 2 compared to group 3 (24%, 37% and 5%, respectively, P  < 0.001). The 30-day mortality data showed significantly better survival after an inverse probability of treatment weighting in group 3, but the 1-year mortality showed no significant differences among the groups (P  = 0.012 and 0.581, respectively). Postoperative complications like the rate of right ventricular assist device (RVAD) implants or re-thoracotomy due to bleeding, postoperative respiratory failure and renal replacement therapy showed no significant differences among the groups. Freedom from the first adverse event like stroke, driveline infection or pump thrombosis during follow-up was not significantly different among the groups. Postoperative blood transfusions within 24 h were significantly higher in groups 1 and 2 compared to surgery on tLVAD support (P  < 0.001 and P  = 0.003, respectively). CONCLUSIONS In our analysis, the transition from tLVAD to dLVAD without further circulatory support did not show a difference in postoperative long-term survival, but a better 30-day survival was reported. The implant using only tLVAD showed a reduction in postoperative transfusion rates, without increasing the risk of postoperative stroke or pump thrombosis. In this small cohort study, our data support the hypothesis that a dLVAD implant on a tLVAD is a safe and feasible technique in selected patients. [ABSTRACT FROM AUTHOR]

This article discusses the outcomes associated with different types of micro-axial flow pumps (mAFPs) used in patients with acute decompensated heart failure who require left ventricular assist device (LVAD) support. The study analyzes data from a multicenter registry and stratifies patients into three groups based on the flow provided by each mAFP variant. The results show that the use of higher-flow mAFPs is associated with improved outcomes, including a reduction in inotropic scores and a decreased incidence of postoperative complications. The study suggests that higher-flow mAFPs may enhance patient recovery and facilitate myocardial unloading. However, there was no statistically significant difference in 30-day mortality between the groups. [Extracted from the article]

Copyright of Canadian Journal of Physiology & Pharmacology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An important complication of the prolonged left ventricle assist device support in patients with heart failure is unloading-induced cardiac atrophy which proved resistant to various treatments. Heterotopic heart transplantation (HTx) is the usual experimental model to study this process. We showed previously that implantation of the newly designed intraventricular spring expander can attenuate the atrophy when examined after HTx in the failing heart (derived from animals with established heart failure). The present study aimed to examine if enhanced isovolumic loading achieved by implantation of the expander would attenuate cardiac post-HTx atrophy also in the healthy heart. Cardiac atrophy was assessed as the ratio of the transplanted-to-native heart weight (HW) and its degree was determined on days 7, 14, 21 and 28 after HTx. The transplantation resulted in 32±3, 46±2, 48±3 and 46±3 % HW loss when measured at the four time points; implantation of the expander had no significant effect on these decreases. We conclude that enhanced isovolumic loading achieved by intraventricular implantation of the expander does not attenuate the development of cardiac atrophy after HTx in the healthy heart. This indicates that such an approach does not represent a useful therapeutic measure to attenuate the development of unloading-induced cardiac atrophy. [ABSTRACT FROM AUTHOR]

The present experiments were performed to evaluate if increased heart tissue concentration of fatty acids, specifically myristic, palmitic and palmitoleic acids that are believed to promote physiological heart growth, can attenuate the progression of unloading-induced cardiac atrophy in rats with healthy and failing hearts. Heterotopic abdominal heart transplantation (HTx) was used as a model for heart unloading. Cardiac atrophy was assessed from the ratio of the native- to-transplanted heart weight (HW). The degree of cardiac atrophy after HTx was determined on days 7, 14, 21 and 28 after HTx in recipients of either healthy or failing hearts. HTx of healthy hearts resulted in 23±3, 46±3, 48±4 and 46±4 % HW loss at the four time-points. HTx of the failing heart resulted in even greater HW losses, of 46±4, 58±3, 66±2 and 68±4 %, respectively (P<0.05). Activation of "fetal gene cardiac program" (e.g. beta myosin heavy chain gene expression) and "genes reflecting cardiac remodeling" (e.g. atrial natriuretic peptide gene expression) after HTx was greater in failing than in healthy hearts (P<0.05 each time). Exposure to isocaloric high sugar diet caused significant increases in fatty acid concentrations in healthy and in failing hearts. However, these increases were not associated with any change in the course of cardiac atrophy, similarly in healthy and post-HTx failing hearts. We conclude that increasing heart tissue concentrations of the fatty acids allegedly involved in heart growth does not attenuate the unloading-induced cardiac atrophy. [ABSTRACT FROM AUTHOR]

Many functions of the cardiovascular apparatus are affected by gender. The aim of our study was find out whether markers of cell death present in the donor myocardium differ in male and female hearts. The study involved 81 patients undergoing heart transplantation from September 2010 to January 2013. Patients were divided into two groups: male allograft (n=49), and female allograft (n=32). Two types of myocardial cell death were analyzed. High-sensitive cardiac troponin T as a necrosis marker and protein bcl-2, caspase 3 and TUNEL as apoptosis markers were measured. We observed a significantly higher level of high-sensitive cardiac troponin T after correcting for predicted ventricular mass in female donors before transplantation as well as in the female allograft group after transplantation throughout the monitored period (P=0.011). There were no differences in apoptosis markers (bcl-2, caspase 3, TUNEL) between male and female hearts before transplantation. Both genders showed a significant increase of TUNEL-positive myocytes one week after transplantation without differences between the groups. Moreover, there were no differences in caspase 3 and bcl-2 expression between the two groups. Our results demonstrated the presence of necrotic and apoptotic cell death in human heart allografts. High-sensitive cardiac troponin T adjusted for predicted ventricular mass as a marker of myocardial necrosis was higher in female donors, and this gender difference was even more pronounced after transplantation. [ABSTRACT FROM AUTHOR]

Microparticles are small circulating vesicles originating from circulatory system and vascular wall cells released during their activation or damage. They possess different roles in regulation of endothelial function, inflammation, thrombosis, angiogenesis, and in general, cellular stress. Microparticles are the subject of intensive research in pulmonary hypertension, atherosclerotic disease, and heart failure. Another recently emerging role is the evaluation of the status of vasculature in end-stage heart failure patients treated with implantable ventricular assist devices. In patients implanted as destination therapy, assessment of the long-term effect of currently used continuous-flow left ventricular assist devices (LVADs) on vasculature might be of critical importance. However, unique continuous flow pattern generated by LVADs makes it difficult to assess reliably the vascular function with most currently used methods, based mainly on ultrasound detection of changes of arterial dilatation during pulsatile flow. In this respect, the measurement of circulating microparticles as a marker of vascular status may help to elucidate both short- and long-term effects of LVADs on the vascular system. Because data regarding this topic are very limited, this review is focused on the advantages and caveats of the circulating microparticles as markers of vascular function in patients on continuous-flow LVADs. [ABSTRACT FROM AUTHOR]

Primary graft dysfunction (PGD) is a life-threatening complication among heart transplant recipients and a major cause of early mortality. Although the pathogenesis of PGD is still unclear, ischemia/reperfusion injury has been identified as a predominant factor. Both necrosis and apoptosis contribute to the loss of cardiomyocytes during ischemia/reperfusion injury, and this loss of cells can ultimately lead to PGD. The aim of our prospective study was to find out whether cell death, necrosis and apoptosis markers present in the donor myocardium can predict PGD. The prospective study involved 64 consecutive patients who underwent orthotopic heart transplantation at our institute between September 2010 and January 2013. High-sensitive cardiac troponin T (hs-cTnT) as a marker of minor myocardial necrosis was detected from arterial blood samples before the donor's pericardium was opened. Apoptosis (caspase-3, active + pro-caspase-3, bcl-2, TUNEL) was assessed from bioptic samples taken from the right ventricle prior graft harvesting. In our study, 14 % of transplant recipients developed PGD classified according to the standardized definition proposed by the ISHLT Working Group. We did not find differences between the groups in regard to hs-cTnT serum levels. The mean hs-cTnT value for the PGD group was 57.4±22.9 ng/l, compared to 68.4±10.8 ng/l in the group without PGD. The presence and severity of apoptosis in grafted hearts did not differ between grafts without PGD and hearts that subsequently developed PGD. In conclusion, our findings did not demonstrate any association between measured myocardial cell death, necrosis or apoptosis markers in donor myocardium and PGD in allograft recipients. More detailed investigations of cell death signaling pathways in transplanted hearts are required. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVAD), currently used in treatment of terminal heart failure, are working on principle of rotary pump, which generates continuous blood flow. Non-pulsatile flow is supposed to expose endothelial cells to high stress and potential damage. Therefore, we investigated longitudinal changes in concentration of circulating endothelial microparticles (EMP) as a possible marker of endothelial damage before and after implantation of LVAD. Study population comprised 30 patients with end-stage heart failure indicated for implantation of the Heart Mate II LVAD. Concentrations of microparticles were measured as nanomoles per liter relative to phosphatidylserine before and 3 months after implantation. At 3 months after implantation we observed significant decrease in concentration of EMP [5.89 (95% CI 4.31-8.03) vs. 3.69 (95% CI 2.70-5.03), p=0.03] in the whole group; there was no difference observed between patients with ischemic etiology of heart failure (n=18) and with heart failure of non-ischemic etiology (n=12). In addition, heart failure etiology had no effect on the rate of EMP concentration decrease with time. These results indicate possibility that LVAD do not cause vascular damage 3 months after implantation. Whether these results suggest improvement of vascular wall function and of endothelium is to be proved in long-term studies. [ABSTRACT FROM AUTHOR]

Ventricular assist devices (VAD) have recently established themselves as an irreplaceable therapeutic modality of terminal heart failure. Because of the worldwide shortage of donors, ventricular assist devices play a key role in modern heart failure therapy. Some clinical data have revealed the possibility of cardiac recovery during VAD application. On the other hand, both clinical and experimental studies indicate the risk of the cardiac atrophy development, especially after prolonged mechanical unloading. Little is known about the specific mechanisms governing the unloading-induced cardiac atrophy and about the exact ultrastructural changes in cardiomyocytes, and even less is known about the ways in which possible therapeutical interventions may affect heart atrophy. One aim of this review was to present important aspects of the development of VADrelated cardiac atrophy in humans and we also review the most significant observations linking clinical data and those derived from studies using experimental models. The focus of this article was to review current methods applied to alleviate cardiac atrophy which follows mechanical unloading of the heart. Out of many pharmacological agents studied, only the selective beta2 agonist clenbuterol has been proved to have a significantly beneficial effect on unloading-induced atrophy. Mechanical means of atrophy alleviation also seem to be effective and promising. [ABSTRACT FROM AUTHOR]

Adipocyte fatty acid binding protein (A-FABP) is a novel adipokine involved in the regulation of lipid and glucose metabolism and inflammation. To evaluate its potential role in the development of postoperative hyperglycemia and insulin resistance we assessed A-FABP serum concentrations and mRNA expression in skeletal and myocardial muscle, subcutaneous and epicardial adipose tissue and peripheral monocytes in 11 diabetic and 20 age- and sex-matched non-diabetic patients undergoing elective cardiac surgery. Baseline serum A-FABP did not differ between the groups (31.1±5.1 vs. 25.9±4.6 ng/ml, p=0.175). Cardiac surgery markedly increased serum A-FABP in both groups with a rapid peak at the end of surgery followed by a gradual decrease to baseline values during the next 48 h with no significant difference between the groups at any timepoint. These trends were analogous to postoperative excursions of plasma glucose, insulin and selected proinflammatory markers. Cardiac surgery increased A-FABP mRNA expression in peripheral monocytes, while no effect was observed in adipose tissue or muscle. Our data suggest that circulating A-FABP might be involved in the development of acute perioperative stress response, insulin resistance and hyperglycemia of critically ill irrespectively of the presence of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Inhalational anesthetics have demonstrated cardioprotective effects against myocardial ischemia-reperfusion injury. Clinical studies in cardiac surgery have supported these findings, although not with the consistency demonstrated in experimental studies. Recent investigations have questioned the advantages of inhalational over intravenous anesthetics with respect to cardiac protection. Ketamine has been shown to be comparable with sufentanil, and has even demonstrated anti-inflammatory properties. Dexmedetomidine has been established as a sedative/anesthetic drug with analgesic properties, and has also demonstrated myocardial protective effects. In this retrospective observational study, the influence of ketamine-dexmedetomidine-based anesthesia (KET-DEX group; n=17) on the release of cardiac biomarkers was compared with that of sevoflurane-sufentanil-based anesthesia (SEVO group; n=21) in patients undergoing elective coronary artery bypass grafting. Compared with the SEVO group, the KET-DEX group exhibited significantly reduced cardiac troponin I (2.22±1.73 vs. 3.63±2.37 µg/l; P=O.02) and myocardial fraction of creatine kinase (CK-MB) levels (12.4±10.4 vs. 20.3±11.2 µg/l; P=O.01) on the morning of the first postoperative day. Furthermore, cardiac troponin I release, evaluated as the area under the curve, was significantly reduced in the KET-DEX group (32.1±20.1 vs. 50.6±23.2; P=O.01). These results demonstrate the cardioprotective effects of ketamine-dexmedetomidine anesthesia compared with those of sevoflurane-sufentanil anesthesia. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) unresponsive to pharmacological intervention is considered a contraindication for orthotopic heart transplantation (OHTX) due to risk of postoperative right-heart failure. In this prospective study, we describe our experience with a treatment strategy of improving severe PH in heart transplant candidates by means of ventricular assist device (VAD) implantation and subsequent OHTX. In 11 heart transplantation candidates with severe PH unresponsive to pharmacological intervention we implanted VAD with the aim of achieving PH to values acceptable for OHTX. In all patients we observed significant drop in pulmonary pressures, PVR and TPG (p<0.001 for all) 3 months after VAD implantation to values sufficient to allow OHTX. Seven patients underwent transplantation (mean duration of support 216 days) while none of patients suffered right-side heart failure in postoperative period. Two patients died after transplantation and five patients are living in very good condition with a mean duration of 286 days after OHTX. In our opinion, severe PH is not a contraindication for orthotopic heart transplantation any more. [ABSTRACT FROM AUTHOR]

We studied the changes in serum fibroblast growth factor-21 (FGF-21) concentrations, its mRNA, and protein expression in skeletal muscle and adipose tissue of 15 patients undergoing cardiac surgery. Blood samples were obtained: prior to initiation of anesthesia, prior to the start of extracorporeal circulation, upon completion of the surgery, and 6, 24, 48, and 96 hours after the end of the surgery. Tissue sampling was performed at the start and end of surgery. The mean baseline serum FGF-21 concentration was 63.1 (43.03-113.95) pg/ml and it increased during surgery with peak 6 hours after its end [385.5 (274.55- 761.65) pg/ml, p<0.001], and returned to baseline value [41.4 (29.15-142.83) pg/ml] 96 hours after the end of the surgery. Serum glucose, insulin, CRP, IL-6, IL-8, MCP-1, and TNF-alpha concentrations significantly increased during the surgery. Baseline FGF-21 mRNA expression in skeletal muscle was higher than in both adipose tissue depots and it was not affected by the surgery. Epicardial fat FGF-21 mRNA increased after surgery. Muscle FGF-21 mRNA positively correlated with blood glucose levels at the end of the surgery. Our data suggest a possible role of FGF-21 in the regulation of glucose metabolism and insulin sensitivity in surgery-related stress. [ABSTRACT FROM AUTHOR]

Inhalational anesthetic-induced preconditioning (APC) has been shown to reduce infarct size and attenuate contractile dysfunction caused by myocardial ischemia. Only a few studies have reported the effects of APC on arrhythmias during myocardial ischemia-reperfusion injury, focusing exclusively on reperfusion. Accordingly, the aim of the present study was to examine the influence of APC on ventricular arrhythmias evoked by regional no-flow ischemia. APC was induced in adult male Wistar rats by 12-min exposures to two different concentrations (0.5 and 1.0 MAC) of isoflurane followed by 30 - min wash-out periods. Ventricular arrhythmias were assessed in the isolated perfused hearts during a 45-min regional ischemia and a subsequent 15-min reperfusion. Myocardial infarct size was determined after an additional 45 min of reperfusion. The incidence, severity and duration of ventricular arrhythmias during ischemia were markedly reduced by APC. The higher concentration of isoflurane had a larger effect on the incidence of ventricular fibrillation than the lower concentration. The incidence of ventricular tachycardia and reversible ventricular fibrillation during reperfusion was also significantly reduced by APC; the same was true for myocardial infarct size. In conclusion, we have shown that preconditioning with isoflurane confers profound protection against myocardial ischemia- and reperfusion-induced arrhythmias and lethal myocardial injury. [ABSTRACT FROM AUTHOR]

Copyright of General Practitioner / Praktický Lékař is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Perinatal hypoxemia may have serious long-term effects on the adult cardiovascular system and may lead to sex-dependent changes in cardiac tolerance to acute ischemia in adult life. The aim of the study was to answer the question whether gonadectomy of the male and female rats in the early phase of ontogenetic development affects the late effect of perinatal hypoxia. Pregnant Wistar rats were placed into a normobaric hypoxic chamber (12 % O2) 7 days before the expected date of delivery. Newborn pups were kept in the chamber with their mothers for another 5 days after birth. After hypoxic exposure all animals were kept for 3 months in room air. Some of the pups were gonadectomized right after removal from the hypoxic chamber. Ventricular arrhythmias were assessed on isolated perfused hearts. Castration did not influence arrhythmogenesis in the adult normoxic or perinatally hypoxic female hearts. Nevertheless, the number of arrhythmias was decreased in perinatally hypoxic gonadectomized males. In conclusion, we have shown that perinatal normobaric hypoxia increased cardiac tolerance to acute ischemia in adult male rats; however, it had no late effect in females. Gonadectomy did not affect arrhythmogenesis in both normoxic and hypoxic female hearts, whereas in males significantly decreased the number of arrhythmias. [ABSTRACT FROM AUTHOR]

Statins are powerful lipid-lowering drugs, widely used in patients with hyperlipidemia and coronary artery disease. It was found, however, that statins appear to have a plelotropic effect beyond their lipid-lowering ability. They exert anti-inflammatory, antithrombotic and antioxidant effects, increase nitric oxide production and improve endothelial dysfunction. The aim of our study was to examine the effect of chronic and acute treatment with simvastatin on the contractile function of the isolated perfused rat heart after ischemia/reperfusion injury. Contractile function was measured on isolated rat hearts, perfused according to Langendorif under constant pressure. The hearts were subjected to 20 mm of global ischemia, followed by 40 mm of reperfusion. To investigate the acute effect, simvastatin at a concentration of 10 pmol/l was added to the perfusion solution during reperfusion. In chronic experiments the rats were fed simvastatin at a concentration of 10 mg/kg for two weeks before the measurement of the contractile function. Acute simvastatin administration significantly increased reparation of the peak of pressure development [(+dP/dt)max] (52.9±8.2 %) after global schemia, as compared with the control group (28.8±5.2 °h). Similar differences were also observed in the time course of the recovery of [(+dP/dt)max]. Chronic simvastatin was without any protective effect. Our results reveal that the acute administration of simvastatin during reperfusion, unlike the chronic treatment, significantly reduced contractile dysfunction induced by ischemia/reperfusion injury. This supports the idea of possible cardioprotective effect of statin administration in the first-line therapy of the acute coronary syndrome. [ABSTRACT FROM AUTHOR]

The article deals with methods for computing the stationary marginal distribution in linear models of time series. Two approaches are described. First, an algorithm based on approximation of solution of the corresponding integral equation is briefly reviewed. Then, we study the limit behaviour of the partial sums c1 η1+c2 η2+···+cn ηn where ηi are i.i.d. random variables and ci real constants. We generalize procedure of Haiman (1998) [Haiman, G., 1998, Upper and lower bounds for the tail of the invariant distribution of some AR(1) processes. Asymptotic Methods in Probability and Statistics, 45, 723-730.] to an arbitrary causal linear process and relax the assumptions of his result significantly. This is achieved by investigating the properties of convolution of densities. [ABSTRACT FROM AUTHOR]

Clinical and experimental studies have repeatedly indicated that overloaded hearts have a higher vulnerability to ischemia/reperfusion injury. The aim of the present study was to answer the question whether the degree of tolerance to oxygen deprivation in hearts of spontaneously hypertensive rats (SHR) may be sex-dependent. For this purpose, adult SHR and their normotensive control Wistar Kyotu (WKY) rats were used. The isolated hearts were perfused according to Langendorff at constant pressure (proportionally adjusted to the blood pressure in vivo). Recovery of contractile parameters (left ventricular systolic, diastolic and developed pressure as well as the peak rate of developed pressure) was measured during reperfusion after 20 min of global no-flow ischemia in 5 min intervals. Mean arterial blood pressure was measured by direct puncture of carotid artery under light ether anesthesia in a separate group of animals. The degree of hypertension was comparable in both sexes of SHR. The recovery of contractile functions in SHR males and females was significantly lower than in WKY rats during the whole investigated period. There was no sex difference in the recovery of WKY animals; on the other hand, the recovery was significantly better in SHR females than in SHR males. It may be concluded that the hearts of female SHR are more resistant to ischemia/reperfusion injury as compared with male SHR. This fact could have important clinical implications for the treatment of cardiovascular disease in women. [ABSTRACT FROM AUTHOR]

It is known (G. Choquet, G. Mokobodzki) that a Baire-one affine function on a compact convex set satisfies the barycentric formula and can be expressed as a pointwise limit of a sequence of continuous affine functions. Moreover, the space of Baire-one affine functions is uniformly closed. The aim of this paper is to discuss to what extent analogous properties are true in the context of general function spaces. In particular, we investigate the function spaceH(U), consisting of the functions continuous on the closure of a bounded open setU⊂ℝm and harmonic onU, which has been extensively studied in potential theory. We demonstrate that the barycentric formula does not hold for the spaceB1b(H(U)) of bounded functions which are pointwise limits of functions from the spaceH(U) and thatB1b(H(U)) is not uniformly closed. On the other hand, every Baire-oneH(U)-affine function (in particular a solution of the generalized Dirichlet problem for continuous boundary data) is a pointwise limit of a bounded sequence of functions belonging toH(U). It turns out that such a situation always occurs for simplicial spaces whereas it is not the case for general function spaces. The paper provides several characterizations of those Baire-one functions which can be approximated pointwise by bounded sequences of elements of a given function space. [ABSTRACT FROM AUTHOR]

The HeartMate 3 (HM3) Long Term Follow Up Study (NCT03022461) is an extension of the original HM3 CE mark study where patients ongoing at 2-year follow-up were reconsented and followed up to 5 years with the aim to evaluate the long-term performance in the patients who continue to be implanted with the HM3 LVAS. Of the 50 patients enrolled in the HM3 CE Mark Study, 5 (10%) patients were transplanted, 1 (2%) was explanted, 12 (24%) expired prior to 24 months, 4 (8%) expired after 24 months but prior to reconsent for the additional follow-ups, 3 (6%) denied their participation to the study extension while 25 (50%) consented for the extended follow-up. To date, of the 25 reconsented patients, 2 patients expired (8%) whereas 23 patients (92%) are still ongoing on support. Additional adverse events collected beyond 2 years included: major bleeding (3 events in 2 patients, 8%) of which 1 (4%) required surgery; major infection (16 events in 8 patients, 32%) of which 8 were driveline infection in 6 pts (32%) and 6 sepsis in 2 patients (8%); ischemic stroke (2 events in 2 pts, 8%), haemorrhagic stroke (1 event in 1 patient, 4%) and right heart failure in 1 patient (4%) which was resolved pharmacologically. No pump thrombosis, hemolysis or gastrointestinal bleeding were reported during the extended follow-up period. At the time of data cut-off, 4 patients (16%) were in NYHA Class I and 6 (24%) in NYHA Class II. Preliminary five years results of the first clinical experience with HM3 LVAS implantation corroborate expected and well acceptable survival and support outstanding hemocompatibility of the device represented by complete absence of pump thrombosis, hemolysis or gastrointestinal bleeding. To the date, 5 years follow-up visits were completed in 10 patients and full longitudinal follow-up will be accomplished by January 2020. [ABSTRACT FROM AUTHOR]

Purpose The MAGENTUM 1 Trial targeted an INR of 1.50-1.90 in patients implanted with HeartMate 3 (HM3) pump. Anticoagulation was maintained in the low intensity range with high efficiency (INR 1.50-1.90, TTR, 75.2 ± 8.6% n=15 patients). None developed thromboembolic events. Factor X activity (FXa) has been suggested as a biologically relevant pharmacodynamic surrogate measure of anticoagulation intensity. We sought to correlate suppression of FXa in MAGENTUM 1 patients to demonstrate the effect of low intensity anticoagulation in HM3 patients. Methods Samples for chromogenic factor X (CFX) assays (Hyphen BioMed) were obtained simultaneously with INR values at routine intervals and stored for batch analysis and not made available to the investigators. Normal reference range for the CFX assay is 71-97%. INR was correlated with CFX; median values and interquartile ranges were determined for INR values >1.50, 1.50-1.90 and <1.90. Results The correlation of INR range with CFX is shown in Figure 1A. The median CFX value for INR range 1.50-1.90 was 40%. When the INRs were above 1.90 the median CFX value was 30%, when the INRs were below 1.50 the median CFX was 53%. Conclusion We demonstrate that a measured INR range of 1.50-1.90 pharmacodynamically corresponds to less suppression of FX activity than at an INR >1.90 but greater than with INR <1.50, indicating an effective range of modulation of the observed anticoagulation effect. We validate the range of low intensity anticoagulation in this analysis and suggest that decreased intensity warfarin monitoring is reliable and may lead to decreased bleeding complications without increasing the risk of thrombosis in patients with HM3 (NCT03078374). [ABSTRACT FROM AUTHOR]

Summary of Objectives The HeartMate 3 Left Ventricular Assist System has demonstrated absence of confirmed de-novo pump thrombosis and reduction in stroke. However, bleeding related adverse events persist under standard anticoagulation targeting a INR range of 2.0-3.0. In an initial experience we demonstrated safety of transition to low intensity anticoagulation (INR target 1.5-1.9, n=15, follow up of at least 6 months). Whether complete cessation of anticoagulation maintains "thromboresistance" in the HeartMate 3 pump remains unknown. Methods We previously reported on a strategy of low-intensity warfarin anticoagulation in patients implanted with HeartMate 3 (J Heart Lung Transplant. 2018;37(5):579-586). Following completion of this study phase, a staged trial was approved by the single site's ethics committee and registered as NCT03704220. All patients enrolled in the low intensity warfarin study (target INR of 1.5-1.9) were considered eligible for enrollment in the "anticoagulation withdrawal" study, if they were continuing on long-term support. All patients had to meet safe eligibility criteria including pump speed reduction to facilitate aortic valve opening (to avoid root thrombus), absence of thrombus in the pre-pump cardiac system, and absence of signs of poor unloading at reduced device speed. Careful surveillance for pump thrombosis was algorithmically mandated with biomarker and serial pump log file analyses. If enrolled, they were withdrawn from warfarin therapy and followed for survival free of pump thrombosis, disabling stroke or major bleeding for at least 3 months as the primary safety end point. Endpoints Enrollment and follow up in the low intensity anticoagulation study has been reported (n=15); 13 men, mean age 57 years (18-72) , with intended goal of therapy of either BTT or DT, INTERMACS Profile mean 3 (2-5), Cardiac Index mean 1.62 l/min/m2. Of 10 patients followed beyond 1 year on reduced anticoagulation, 5 patients have qualified for complete withdrawal of anticoagulation and the safety endpoint analysis will be completed prior to the ISHLT meeting in March 2019. This pivotal study is the first indication-independent anticoagulation withdrawal study in the HeartMate 3 designed to establish thrombo-resistance for the device and form the rationale for a large scale multicenter trial. [ABSTRACT FROM AUTHOR]

Introduction Bioprosthetic heart valves (BV) made of xenogenic pericardium fixed with glutaraldehyde have been developed more than 30 years ago. The concept of cross linking collagenous fibers to ensure in-vivo stability of the scaffold and reducing antigenic immune response by fixation resulted in successful clinical evaluations and a lower risk of thromboembolism thus eliminating the need for a lifelong anticoagulation. To explain these clinical results, an acquired hemocompatibility process has been proposed but never extensively studied because of the impossibility to access not degenerated material. Objective To study and understand mechanisms of acquired hemocompatibility, we explored non degenerated BV from 9 different patients implanted with a Carmat total artificial heart (C-TAH) and four BV duration from 45 to 270 days. Method We performed classic histopathology and immunophenotypic characterization of explanted BV. Biological deposit has been also explored by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Result In short implantation duration time, we observed a fibrin deposit with inflammatory cells and pseudotubes formation. Histological sections showed superficial infiltration of cells, persisting in long duration but not damaging integrity of the pericardium. The fibrin deposit is then organized in a compacted smooth fibrin network in longer implantation durations. Endothelial cells (EC) monolayer covering has also been observed on this fibrin cap, the percentage of the BV surface with EC covering increasing along months. This endothelial cells covering is positive for VE-Cadherin, with flat nucleus and tight junctions. Conclusion Healthy BV implanted with C-TAH enabled us to study, for the first time, non-degenerated implanted valve in human. Biomaterial passivation by an organized fibrin deposit and formation of EC monolayer on top achieve an optimal hemocompatibility without any modification of pericardial tissue. [ABSTRACT FROM AUTHOR]