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... Newer generation continuous flow (cf) devices have decreased intrapump clearances and require a combination of oral vitamin K antagonists and specific antiplatelet therapy. Despite this intensity of antithrombotic therapy, there have been multiple documented cases of pump thrombus in axial flow LVADs (4)(5)(6)(7), as well as in centrifugal cf-LVADs (8)(9)(10). We report the risk factors and outcomes of a series of five patients out of our total of 51 consecutive patients implanted with the centrifugal Heart-Ware LVAD treated with intravascular thrombolysis. ...
... Four recent series have documented pump replacement for LVAD thrombosis (10,(12)(13)(14). In the Heartmate-II clinical trial (an axial cf-LVAD), pump thrombus managed with device replacement occurred in 1.4% of patients equating to an event rate of 2.2 per 100 patient-years of support (12). ...
... Initial subanalysis of the ADVANCE data suggested that those with lower INR and lower doses of aspirin were more likely to suffer pump thrombosis (16). In the Bad Oeynhausen HeartWare series, four out of six pump thromboses were treated with pump replacement (10). In that series, thrombolysis was successful in only one out of two patients who received it. ...
Article
The current recommended anticoagulation regimen during continuous flow centrifugal left ventricular device support is a combination of antiplatelet therapy as well as oral anticoagulation. Despite this, pump thrombosis occurs in rare situations. We report the risk factors and nonsurgical management and outcomes of five patients implanted with continuous flow centrifugal left ventricular assist devices who displayed clinical, hemodynamic, and laboratory features of intrapump thrombosis. This information may support the use of intravenous thrombolytics for suspected pump thrombus in these newer generation devices.
... The annual rate of CF-LVAD replacement due to PT can reach 0.06%, and can be associated with high morbidity and mortality rates [1]. Though good outcomes have been reported after device replacement in experienced surgical centers [3], a decrease in survival and a higher incidence of infections and neurological events have been found when compared with the first implantation outcomes [1,[3][4][5]. ...
... The annual rate of CF-LVAD replacement due to PT can reach 0.06%, and can be associated with high morbidity and mortality rates [1]. Though good outcomes have been reported after device replacement in experienced surgical centers [3], a decrease in survival and a higher incidence of infections and neurological events have been found when compared with the first implantation outcomes [1,[3][4][5]. ...
... Thrombolytic therapy has been proposed as an alternative treatment in CF-LVAD thrombosis [1][2][3][4][5]. ...
... Several groups have suggested intracavitatory thrombolytic therapy through a catheter in the left ventricle with the view to reduce its systemic side effects [16]. However, Aissaoui et al. disagree on the benefits of thrombolytic therapy and prefer device exchange, though associated with significantly higher mortality [18,19]. In this series, all patients with device failures underwent a surgical LVAD exchange through median sternotomy with an aceptable outcome. ...
... In this series, all patients with device failures underwent a surgical LVAD exchange through median sternotomy with an aceptable outcome. Furthermore, there are few reports in the literature on pump exchange using minimally invasive access with similar outcomes compared with full sternotomy [18,20]. However, due to a higher mortality in this challenging patient group, minimally invasive access for LVAD exchange represents a surgical challenge and is limited to experienced high-volume centres. ...
Article
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Objectives: Left ventricular assist devices (LVADs) are a routine treatment for patients with advanced heart failure as a bridge to transplantation. The aim of this study was to present our institutional experience and mid-term outcomes after implantation of 139 continuous-flow (cf) LVADs as a bridge to transplantation. Methods: One hundred and thirty-nine consecutive LVAD implantations were performed in our institution between July 2007 and August 2013. The mean age of the population was 44.0 ± 13.7 years and 24 (17%) of the patients were female. A substantial number of the patients were on preoperative mechanical support: 35 (25%) with an intra-aortic balloon pump, 9 (6.5%) with an extracorporeal membrane oxygenator and 25 (18%) with previous LVAD, for LVAD exchange. Results: The mean support duration was 514 ± 481 days, whereas the longest support duration was 2493 days (>6 years). The overall cumulative survival rate following cfLVAD implantation was 89% at 30 days, 76% at 1 year and 66% at 2 years (Fig. 1). There was a statistically significant difference in survival in favour of first LVAD implantation compared with VAD exchange: 91 vs 80% at 30 days, 79 vs 57% at 1 year and 70 vs 43% at 2 years (log-rank P = 0.010). Postoperatively, patients had a significant improvement in end-organ function 1 month after LVAD implantation. In addition, comparison of two different devices [HeartMate II (HM II) and HeartWare] using propensity score matching showed no significant differences in survival and most postoperative adverse events. However, patients supported with HM II required significantly more units of fresh frozen plasma (P = 0.020) with a trend towards a higher use of red blood cells (P = 0.094), and were also more likely to develop percutaneous site infections (P = 0.022). Conclusions: HM II and HeartWare cfLVADs have excellent early postoperative outcomes and good mid-term survival, despite a considerable number of patients needing VAD exchange.
... 9,10,17 While appropriate adjustments to HVAD's operating specifications have reported success supporting right heart failure and pediatric patients, it is potentially associated with a high rates of major adverse events; multisystem organ failure, neurologic dysfunction, respiratory failure, pump thrombosis, infection, stroke, and major bleeding. 10,[18][19][20][21][22] This study was designed to evaluate the effect of HVAD on hemolysis, platelet activation and vWF degradation in adult systemic, pediatric systemic and adult pulmonary flow conditions. Following the standard practice for assessing blood damage in continuous-flow pumps per ASTM F1841-97, this study aimed to provide benchmark values for future RVAD and pediatric LVAD development. ...
... Pump thrombosis is a major complication that is common in all HVAD implantations, particularly in pediatric systemic and adult pulmonary patients where the low flow state potentially increases stagnant regions of blood within the pump. 19,33,34 However, bovine platelets have been shown to be less susceptible to shear stress than human platelets and a shear rate threshold must be reached to activate platelets. 35 It is likely that the experiments conducted did not produce enough shear stress for bovine platelet activation, especially given the short run times of 6 hours. ...
Article
Full-text available
The development of adult use right ventricular assist devices (RVADs) and pediatric left ventricular assist devices (pediatric LVADs) have significantly lagged behind compared to adult use left ventricular assist devices (LVADs). The HeartWare ventricular assist device (HVAD) intended to be used for adult's systemic support, is increasingly used off-label for adult pulmonary and pediatric systemic support. Due to different hemodynamics and physiology, however, the HVAD's hemocompatibility profiles can be drastically different when used in adult pulmonary circulation or in children, compared to its intended usage state, which could have a direct clinical and developmental relevance. Taking these considerations in mind, we sought to conduct in vitro hemocompatibility testing of HVAD in adult systemic, pediatric systemic and adult pulmonary support conditions. Two HVADs coupled to custom-built blood circulation loops were tested for 6 hours using bovine blood at 37°C under adult systemic, pediatric systemic, and adult pulmonary flow conditions (flow rate = 5.0, 2.5, and 4.5 L/min; differential pressure = 100, 69, and 20 mm Hg, respectively). Normalized index of hemolysis for adult systemic, pediatric systemic, and adult pulmonary conditions were 0.0083, 0.0039, and 0.0017 g/100 L, respectively. No significant difference was seen in platelet activation for these given conditions. High molecular weight von Willebrand factor multimer degradation was evident in all conditions (p < 0.05). In conclusion, alterations in the usage mode produce substantial differences in hemocompatibility of the HVAD. These findings would not only have clinical relevance but will also facilitate future adult use RVAD and pediatric LVAD development.
... Medical management for pump thrombosis is associated with a high morbidity, high proportion of treatment failures, and the need for pump exchange when balanced with a modest success rate, especially if the onset of the thrombosis is>24 hours. 173, 174 Starling reported a 50% mortality in those initially treated medically, compared with a 2.3% mortality in those who underwent immediate device replacement. 153 The decision to use pharmacologic treatment in the management of device thrombosis and the specific selection of drugs used is actually device and center specific. ...
... Intravenous thrombolysis 174,[180][181][182][183][184][185] is associated with an important risk of severe bleeding complications (eg, hemorrhagic stroke), but can be considered if a patient is not a surgical candidate. 13,162,173,176,179,182,184,185 Intraventricular thrombolysis 169,180,[186][187][188][189][190][191] should be also be used with extreme caution because of the risk of severe bleeding, but can be considered if the patient is not a surgical candidate. 162,169,171,187,188,[190][191][192] ...
... However, the surgical pump exchange with or without cardiopulmonary bypass is associated with mortality or complications such as bleeding or wound infection. This procedure was also performed during the first episode of device thrombosis in this patient, and it has been shown by our group that it can be performed safely with acceptable risk for the patient [3]. The off-pump exchange seems to be associated with a smaller operative risk [3], but its disadvantage is the obstructed and reduced vision inside the left ventricular cavity to rule out ventricular thrombi. ...
... This procedure was also performed during the first episode of device thrombosis in this patient, and it has been shown by our group that it can be performed safely with acceptable risk for the patient [3]. The off-pump exchange seems to be associated with a smaller operative risk [3], but its disadvantage is the obstructed and reduced vision inside the left ventricular cavity to rule out ventricular thrombi. However, numbers of treated patients are still fairly small, and therefore a final recommendation on which strategy is the superior approach is not possible at this time. ...
Article
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Here we present a patient after implantation of a left ventricular assist device (HeartWare) for destination therapy complicated by recurrent thrombosis of the device. At 14 months after implantation, the patient presented with a pump thrombosis after an INR incompliance period. A surgical pump exchange was performed and the patient recovered uneventfully. Five months later a pump thrombosis occurred again, and the patient refused surgery. Systemic thrombolysis was carried out this time. Three and 6 months later the same clinical picture was presented again, and repeat thrombolysis was performed successfully. The patient was discharged and has remained stable since, without any symptoms of thrombosis of the device.
... Decreasing right ventricular assist device (RVAD) pump speed to below manufacturer's specifications moves away from the design point for pump function, and can influence pump washout and thus thrombus formation within the pump (7). Furthermore, with hydrodynamic suspension of the impeller within the device, insufficient pump speed may lead to impeller instability (7). ...
... Decreasing right ventricular assist device (RVAD) pump speed to below manufacturer's specifications moves away from the design point for pump function, and can influence pump washout and thus thrombus formation within the pump (7). Furthermore, with hydrodynamic suspension of the impeller within the device, insufficient pump speed may lead to impeller instability (7). Previous in vitro studies on biventricular support using dual LVADs had already established the benefits of outflow cannula restriction and rotational speed reduction. ...
Article
Implantable left ventricular assist devices (LVADs) have been adapted clinically for right-sided mechanical circulatory support (RVAD). Previous studies on RVAD support have established the benefits of outflow cannula restriction and rotational speed reduction, and recent literature has focused on assessing either the degree of outflow cannula restriction required to simulate left-sided afterload, or the limitation of RVAD rotational speeds. Anecdotally, the utility of outflow cannula restriction has been questioned, with suggestion that banding may be unnecessary and may be replaced simply by varying the outflow conduit length. Furthermore, many patients have a high pulmonary vascular resistance (PVR) at the time of ventricular assist device (VAD) insertion that reduces with pulmonary vascular bed remodeling. It is therefore important to assess the potential changes in flow through an RVAD as PVR changes. In this in vitro study, we observed the use of dual HeartWare HVAD devices (HeartWare Inc., Framingham, MA, USA) in biventricular support (BiVAD) configuration. We assessed the pumps' ability to maintain hemodynamic stability with and without banding; and with varying outflow cannulae length (20, 40, and 60 cm). Increased length of the outflow conduit was found to produce significantly increased afterload to the device, but this was not found to be necessary to maintain the device within the manufacturer's recommended operational parameters under a simulated normal physiological setting of mild and severe right ventricular (RV) failure. We hypothesize that 40 cm of outflow conduit, laid down along the diaphragm and then up over the RV to reach the pulmonary trunk, will generate sufficient resistance to maintain normal pump function.
... Multiple conflicting reports have been published regarding the use of fibrinolytics for both centrifugal and axial flow CF-LVADs. [31][32][33][34][35][36][37][38][39][40][41][42] Fibrinolytics have been administered both systemically as well as intraventricularly, and given the expected differences in dosing and systemic exposure, the results of these 2 distinct regimens should be assessed independently when possible. The majority of the published fibrinolytic data are from the Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure (ADVANCE) trial analysis of the HeartWare HVAD, 13 which described tissue plasminogen activator (tPA) use in 19 patients (systemic: n ¼ 8, intraventricular: n ¼ 7, and unreported: n ¼ 4). ...
... Although treatment was successful in one patient, the other patient experienced a significant driveline-related bleeding necessitating surgical intervention. 38 A final case report exists of successful systemically administered tPA as a continuous infusion at 0.1 mg/kg/h for 1.5 hours, with resolution of power elevations and device flow. 41 Intraventricular use of tPA has been successfully reported in 4 separate case reports with the HeartWare HVAD, all of which utilized 1 mg/min of tPA until thrombus resolution as evidence by pump dynamics (power, flow). ...
Article
Advanced heart failure therapy has been revolutionized with the advent of continuous-flow ventricular assist devices (CF-LVADs) which have improved both survival and quality of life. Despite this, support with CF-LVADs is frequently complicated, with 70% of recipients experiencing a major complication in the first year of durable support. The most concerning of these complications to emerge is device-related thrombosis, which is associated with increased morbidity and mortality. Pathophysiology and diagnosis are multifaceted and complex, with pump-specific and patient-specific factors to be considered. Incidence estimates are evolving with increases seen in the past 2 years compared with earlier implant data. Evidence for treatment is limited to case series and reports, which are subject to significant publication bias. Finally, appropriate primary and secondary prophylaxis is imprecise with multiple antiplatelet and antithrombotic strategies described. This review seeks to summarize the current literature surrounding the pathophysiology, diagnosis, and management of thrombosis in CF-LVAD recipients.
... Whereas transplantation is challenged by the complications of rejection, infection, malignancy, and allograft vasculopathy 14 the adverse event profile of the MCS patient is dominated by device-related infection, bleeding events, right heart failure, central nervous system events, and device malfunction. 9,15,10 . The concept of adverse event burden 8 (see again Table 4) might provide a unifying method of expressing the overall adverse event impact of each therapy, but ultimately the patient will need to participate in therapy selection based, in part, on a subjective analysis of the relevant adverse event profile and how that might impact life satisfaction. ...
Article
Average 2-year survival after cardiac transplantation is approximately 80%. The evolution and subsequent approval of larger pulsatile and, more recently, continuous flow mechanical circulatory support (MCS) technology for destination therapy (DT) offers the potential for triage of some patients awaiting cardiac transplantation to DT. The National Heart, Lung, and Blood Institute Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a national multi-institutional study of long-term MCS. Between June 2006 and December 2011, 127 pulsatile and 1160 continuous flow pumps (24% of total primary left ventricular assist devices [LVADs]) carried an initial strategy of DT therapy. By multivariable analysis, risk factors (P < .05) for mortality after DT included older age, larger body mass index, history of cancer, history of cardiac surgery, INTERMACS level I (cardiogenic shock), dialysis, increased blood urea nitrogen, use of a pulsatile flow device, and use of a right ventricular assist device (RVAD). Among patients with a continuous flow LVAD who were not in cardiogenic shock, a particularly favorable survival was associated with no cancer, patients not in cardiogenic shock, and blood urea nitrogen less than 50 mg/dL, resulting in 1- and 2-year survivals of 88% and 80%. (1) Evolution from pulsatile to continuous flow technology has dramatically improved 1- and 2-year survivals; (2) DT is not appropriate for patients with rapid hemodynamic deterioration or severe right ventricular failure; (3) important subsets of patients with continuous flow DT now enjoy survival that is competitive with heart transplantation out to about 2 years.
... Explantation of conventional full support LVADs is technically challenging and time-consuming procedure due to re-do sternotomy and location of pump in the pericardium. It may require cardio-pulmonary bypass (CPB), cause significant blood loss and is associated with high mortality and morbidity [5,6]. ...
Article
Full-text available
Synergy(®) micropump was implanted as a bridge to heart transplantation in a middle-age lady with chronic advanced heart failure due to dilated cardiomyopathy. After a good initial recovery, patient was discharged to ward, where her stay was prolonged due to non-healing operative wound over the micropump and recurrent gastrointestinal bleeding. After 3 months of therapy, the heart seemed to be recovered and the micropump was explanted. In view of the patient's bleeding tendency, the micropump was explanted in staged manner.
... Exchange or explantation of full-support LVADs is a technically challenging and time consuming procedure due to redo sternotomy and location of pump inside the pericardium. It may require CPB, cause significant blood loss and is associated with high mortality and morbidity [29,30]. Due to its unique location in right infra-clavicular pocket, exchange of Synergy Micro-pump is an easy surgery. ...
Article
Full-text available
The discrepancy between the number of patients on the waiting list and available donor hearts has led to the successful development of left ventricular assist devices (LVAD) as a bridge to transplantation. The conventional LVADs are designed to provide full hemodynamic support for the end-stage failing heart. However, full-support LVAD implantation requires major surgery, sternotomy and cardiopulmonary bypass in majority of cases. The Synergy Micro-pump is the smallest implantable LVAD and provides partial flow support up to 3 l/min. It was shown that early intervention with this device can provide substantial benefits to patients with severe heart failure not yet sick enough for a full-support LVAD. Due the small dimensions it can be implanted without cardiopulmonary bypass or a sternotomy. The purpose of this article is to review the clinical use of the Synergy Micro-pump as partial hemodynamic support.
... cases. There is no consensus about the treatment of device thrombosis, with thrombolytic therapy being favoured as a first-line treatment by many, followed by device exchange which is associated with high mortality [5,6]. Taking into consideration the large size of the cohort, it would be insightful if the authors could comment on their institutional protocol for the management of device thromboses especially whether thrombolysis was tried before device exchange and the success rate of both thrombolysis and surgery for device exchange. ...
Article
Full-text available
We congratulate Wu et al. [1] for sharing their experience with the HeartWare ventricular assist device (HVAD), which is the largest published series so far. They were successful in demonstrating improvement not only in haemodynamic parameters but also in renal and liver function after device implantation. In comparison with previously published multicentre trials and single-centre experiences about the use of the HVAD [2–4], this series is unique due to liberalization of inclusion criteria, i.e. inclusion of destination therapy patients, younger ( 65 years) are similar to those in the 18–65 age group. Another noteworthy finding is the significant reduction in mean pulmonary vascular resistance (PVR) from 9 to 3 Wood units, which demonstrates the efficacy of LVADs, in this case HAVD, in reducing PVR and thus making patients, who were denied heart transplantation (HTx) previously due to high PVR, suitable for HTx. The series might be criticized for survival outcome (67% at 1 year) which is lower compared with the published 84–86% [2–4]. However, the stringent patient inclusion criteria in the previous trials differ markedly from those in the present series. Specifically, implantation for destination therapy (59% survival at 1 year) and BVAD (47% survival at 1 year) significantly influence their results and are responsible for overall lower survival. Also, the proportion of patients in INTERMACS level I and II published trials is only 22–29%, while it makes up two-thirds of the patients in this series. However, a relatively poor survival, 67% at 3 months and 67% at 1 year (suggestive of only early deaths in this group), is observed in INTERMACS level IV patients in this series. It will be much appreciated if authors could explain these results. Thrombosis in the LVAD pumps is an infrequent but annoying complication and the HVAD is not an exception with the reported incidence of pump thrombosis ranging from 2.1 to 9% [2–4].In the present series, the authors report device malfunctions in 12 (8.5%) cases. There is no consensus about the treatment of device thrombosis, with thrombolytic therapy being favoured as a first-line treatment by many, followed by device exchange which is associated with high mortality [5, 6]. Taking into consideration the large size of the cohort, it would be insightful if the authors could comment on their institutional protocol for the management of device thromboses especially whether thrombolysis was tried before device exchange and the success rate of both thrombolysis and surgery for device exchange.
... Ein "komplettes" Kunstherz (TAH) unterscheidet sich von den Linksherzunterstützungssystemen dadurch, dass das Herz des Patienten operativ vollständig entfernt und durch 2 Kunstventrikel ersetzt wird. Indikationen zur Implantation eines TAH im Vergleich zu einem LVAD sind das biventrikuläre Herzversagen, das akute Herzversagen aufgrund eines massiven Myokardinfarkts, bei dem die Implantation einer Einflusskanüle häufig nicht möglich ist, und die Herzinsuffizienz mit intrakardialen Thromben [49]. Zurzeit ist das einzige klinisch einsetzbare Kunstherzsystem das Syncardia-TAH. ...
Article
In fast allen westlichen industrialisierten Ländern betrifft die terminale Herzinsuffizienz immer mehr Menschen. Nach wie vor ist die orthotope Herztransplantation dabei die „chirurgische“ Therapie der Wahl. Der Mangel an Spenderorganen und der technische Fortschritt führten in den letzten 20 Jahren zu chirurgischen organerhaltenden Strategien und Therapien, mit denen eine anstehende Herztransplantation hinausgezögert oder sogar vermieden werden kann. Heute können bestimmte Patienten mit ischämischer Kardiomyopathie oder Mitralklappeninsuffizienz trotz deutlich reduzierter Ventrikelfunktion mit einem akzeptablen Risiko operiert werden. Zusätzlich ist der Mitraclip für diese Patienten eine weitere therapeutische Alternative. Außerdem wurden Rekonstruktionsverfahren des linken Ventrikels in großen klinischen Studien wie RESTORE oder STICH untersucht – und werden kontrovers diskutiert. Weiterentwickelte Herzunterstützungssysteme werden nicht nur als Überbrückungssysteme zur Herztransplantation angewendet, sondern auch als Dauertherapie bei terminaler Herzinsuffizienz. In der vorliegenden Übersichtsarbeit werden die verschiedenen Verfahren, insbesondere deren Anwendung, Differenzialindikation und Komplikationen erläutert.
... The anticoagulation protocol for the HVAD recommends maintaining an INR of 2.0 to 3.0. Despite the advantages of the HVAD, the rates of thrombus formation and suspected thromboembolic events can reach up to 8% [36,58]. The ADVANCE investigators reviewed 382 patients who underwent HVAD implantation. ...
Article
The importance of mechanical circulatory support in the therapy of advanced heart failure is steadily growing. The rapid developments in the field of mechanical support are characterized by continuous miniaturization and enhanced performance of the assist devices, providing increased pump durability and prolonged patient survival. The HeartWare left ventricular assist device system (HeartWare Inc., Framingham, MA, USA) is a mechanical ventricular assist device with over 8000 implantations worldwide. Compared with other available assist devices it is smaller in size and used in a broad range of patients. The possibility of minimally invasive procedures is one of the major benefits of the device - allowing implants and explants, as well as exchanges of the device with reduced surgical impact. We present here a review of the existing literature on the treatment of advanced heart failure using the HeartWare left ventricular assist device system.
... There were 20 reported deaths in this group of patients. 4,15,25,26,[38][39][40][41][42][43][44][45][46]48,[50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] Thrombolytics were used as a triple or a quadruple drug therapy (i.e., in combination with IV UFh and either GPIIb/IIIa inhibitor or direct thrombin inhibitor) in 18 patients resulting in a complete resolution in 56% (10/18) of patients. There were six major bleeding events and one minor bleeding event. ...
Article
Full-text available
Pump thrombosis is a dreaded complication of left ventricular assist device (LVADs). We completed a systematic review to evaluate the efficacy and complications associated with medical management of LVAD thrombosis. Databases were searched using the terms "vad*" or "ventricular assist device" or "heart assist device" and "thrombus" or "thrombosis" or "thromboembolism". Of 2383 manuscripts, 49 articles met the inclusion criteria. The risk of partial or no resolution of LVAD thrombosis did not significantly differ between thrombolytic and non-thrombolytic regimens (OR 0.48; 95% CI 0.20-1.16). When response to therapy was evaluated based upon pump type, there were no significant differences in how patients with a HMII or HVAD responded to thrombolytic or non-thrombolytic treatment. Pooled risk of major bleeding in the thrombolytic group was 29% (95% CI 0.17-0.44) and 12% (95% CI 0.01-0.57) in the non-thrombolytic group. Odds of death did not differ between thrombolytic and non-thrombolytic regimens (OR 1.28; 95% CI 0.42-3.89). Although thrombolytic and non-thrombolytic treatment similarly resolved LVAD thrombosis, major hemorrhage may be increased with use of thrombolysis. Randomized clinical trials comparing thrombolytic and non-thrombolytic treatment of LVAD thrombosis are needed to establish the most effective and safe option for patients who are not surgical candidates.
... There were 20 reported deaths in this group of patients. 4,15,25,26,[38][39][40][41][42][43][44][45][46]48,[50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] Thrombolytics were used as a triple or a quadruple drug therapy (i.e., in combination with IV UFh and either GPIIb/IIIa inhibitor or direct thrombin inhibitor) in 18 patients resulting in a complete resolution in 56% (10/18) of patients. There were six major bleeding events and one minor bleeding event. ...
Article
Full-text available
Introduction: Left ventricular assist device (LVAD) is being increasingly utilized in patients with advanced heart failure both as bridge to heart transplantation and as destination therapy. Intracranial hemorrhage (ICH) is one of major complications associated with LVAD. However, current trends on utilization of LVAD and associated ICH in real world practice are not known. Methods: We analyzed patients in the Nationwide Inpatient Sample (NIS) between 2007 and 2011. Heart failure patients with LVAD were identified from the database and patients with discharge diagnosis of ICH were compared to those without ICH. Trends and outcomes of ICH in patients with LVAD were analyzed. In addition, predictors of ICH were identified using a multivariate regression model. Results: We identified 20,443 discharges with a primary diagnosis of heart failure with LVAD of which 447 patients had a co-diagnosis of ICH. We saw a significant increase in discharge diagnosis of heart failure with LVAD from 1232 discharges in 2007 to 6308 in 2011 (p&lt0.001)(Figure). However, the incidence of ICH in this patient population decreased from 3.9% in 2007 to 2.4% in 2011. On multivariate analysis, in-hospital mortality was significantly higher in the ICH group (OR: 9.5, P=0.0001). After adjustment for potential confounders age &lt35 years (OR: 2.4, P=0.01) and a rising Charlson co-morbidity index score were independent predictors of ICH whereas presence of diabetes (OR: 0.05, P=0.001), chronic lung disease (OR:0.07, P=0.001), renal disease (OR: 0.09, P=0.001) and peripheral vascular disease (OR: 0.12, P=0.002) were found to be protective of ICH. Conclusions: Our analysis indicates an increasing trend in utilization of LVAD but a decrease in incidence of ICH over the same period. ICH was found to increase risk of mortality by nearly 10 fold. Increasing comorbidity burden increases the risk of ICH whereas age and certain individual co-morbidities appear to have a paradoxical effect on risk of ICH.
... [11]. Even if an increase in pump thrombosis reported in previous studies [12][13][14] has been mitigated in recently published trials [15,16], pump thrombosis may be a vexing problem because of older patients and longer duration of life after implantation. Device manufacturers usually suggest the use of a specific antiplatelet or anticoagulant agent, without any strong evidence supporting their indication. ...
Article
Full-text available
Platelets play a key role in the pathogenesis of ventricular assist device (VAD) thrombosis; therefore, antiplatelet drugs are essential, both in the acute phase and in the long-term follow-up in VAD management. Aspirin is the most used agent and still remains the first-choice drug for lifelong administration after VAD implantation. Anticoagulant drugs are usually recommended, but with a wide range of efficacy targets. Dual antiplatelet therapy, targeting more than one pathway of platelet activation, has been used for patients developing a thrombotic event, despite an increased risk of bleeding complications. Although different strategies have been attempted, bleeding and thrombotic events remain frequent and there are no uniform strategies adopted for pharmacological management in the short and mid- or long-term follow up. The aim of this article is to provide an overview of the evidence from randomized clinical trials and observational studies with a focus on the pathophysiologic mechanisms underlying bleeding and thrombosis in VAD patients and the best antithrombotic regimens available.
... Reduced speed 7-9 and banding 10-14 have successfully supported patients in previous trials, though high rates of major adverse events were reported; these include multisystem organ failure, respiratory failure, pump thrombosis, infection, stroke, and gastrointestinal bleeding. 2,11,[15][16][17][18] There is an urgent need for the development of long-term RVADs that are specifically designed for the unique characteristic of pulmonary circulation. When developing a ventricular assist device (VAD), hemocompatibility is one of the most critical elements for assessment. ...
... Bleeding is the most frequent adverse event in the presence of LVAD and is favored by high LVAD flows and mean arterial pressure > 90 mm Hg [30][31][32]. Pump thrombosis and arterial thromboembolism occur in approximately 8% of patients per year and may develop even in adequately anticoagulated patients [30,33]. As confirmed by Nguyen et al. [34], preoperative inflammatory status, abnormal platelet counts and higher CHA2DS2-Vasc score (at least 1 considering HF) are all risk factors for thromboembolic events, pump thrombosis and stroke. ...
Article
Full-text available
The use of left ventricular assist devices (LVADs), whether for destination therapy or bridge to transplantation, has gained increasing validation in recent years in patients with advanced heart failure. Arrhythmias can be the most challenging variables in the management of such patients but the main attention has always been focused on ventricular arrhythmias given the detrimental impact on mortality. Nevertheless, atrial fibrillation (AF) is the most common rhythm disorder associated with advanced heart failure and may therefore characterize the LVADs’ pre- and postimplantation periods. Indeed, the consequences of AF in the population suffering from standard heart failure may require a more comprehensive evaluation in the presence of or in sight of an LVAD, making the AF clinical management in these patients potentially complex. Several studies have been based on this subject with different and often conflicting results, leaving many questions unresolved. The purpose of this review is to summarize the main pieces of evidence about the clinical impact of AF in LVAD patients, underlining the main implications in terms of hemodynamics, thromboembolic risk, bleeding and prognosis. Therapeutic considerations about the clinical management of these patients are also made according to the latest evidence.
... 11,17 There is a growing number of mostly single-center studies describing medical management of pump thrombosis. 15,[18][19][20] The management of pump thrombosis in the ADVANCE BTT+CAP trial was left up to the discretion of the individual centers. Interestingly, the rate of pump exchange for pump thrombus was significantly lower in the CAP cohort compared to the BTT cohort. ...
Article
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Background The HeartWare left ventricular assist device (HVAD) is the first implantable centrifugal continuous flow pump approved for use as a bridge to transplantation. An infrequent but serious adverse event of LVAD support is thrombus ingestion or formation in the pump. In this study we analyze the incidence of pump thrombus, evaluate the comparative effectiveness of various treatment strategies and examine factors predisposing to development of pump thrombus. Methods A total of 382 patients who underwent implantation of the HVAD as part of the ADVANCE Bridge to Transplant (BTT) and subsequent Continued Access Protocol (CAP) were included in this analysis. Descriptive statistics and group comparisons were generated to analyze baseline characteristics, incidence of pump thrombus and treatment outcomes. A multivariate analysis was performed to assess significant risk factors for developing pump thrombus. Results There were 34 pump thrombus events observed in 31 patients (8.1% of the cohort) for a rate of 0.08 events per patient year. The incidence of pump thrombus did not differ between BTT and CAP. Medical management of pump thrombus was attempted in 30 cases, and was successful in 15 cases (50%). A total of 16 patients underwent pump exchange and 2 underwent urgent transplantation. Five patients with a pump thrombus died after failing medical therapy, 4 of whom also underwent a pump exchange. Survival at 1 year in patients with and without a pump thrombus was 69.4% and 85.5% (P=0.21). A multivariable analysis revealed that significant risk factors for pump thrombus included a mean arterial pressure ≥90 mm Hg, aspirin dose of 81 mg or less, INR less than 2, and INTERMACS Profile level of 3 or greater at implant. Conclusions Pump thrombus is a clinically important adverse event in patients receiving an HVAD occurring at a rate of 0.08 events per patient year. Significant risk factors for pump thrombosis include elevated blood pressure and suboptimal anticoagulation and antiplatelet therapies. This suggests that pump thrombus event rates could be reduced through careful adherence to patient management guidelines.
Article
Pump thrombosis is a dreaded complication of long-term implantable ventricular assist devices. No guidance exists regarding the diagnosis and management of this entity despite its significant morbidity. After considerable thought and deliberation, a group of leading investigators in the field of mechanical support propose an algorithm for the diagnosis and management of this vexing entity based on clinical symptoms and serologic and imaging studies. © 2013 International Society for Heart and Lung Transplantation. All rights reserved.
Article
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Despite technological advances in a newer generation of ventricular assist devices (VAD), complications, such as pump thromboses, remain a significant cause of morbidity and indeed mortality in these patients. We present the case of a 34-year old patient who underwent HeartAssist 5 (HA5) implantation as a bridge to cardiac transplant. After an initial uneventful recovery, he developed a pump thrombosis that was refractory to medical treatment. We present the surgical technique used to exchange the HA5 with a HeartWare (HVAD), leaving the old inflow-sewing ring in situ.
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Left ventricular assist device (LVAD) implantation is associated with the risk of early postoperative right heart dysfunction, which may require urgent institution of mechanical right ventricular support. This is conventionally achieved by cannulation of the femoral vein or right atrial appendage for the inflow and the pulmonary artery for the outflow. However, this requires resternotomy with increased risk of wound and device infection, as well as excessive bleeding. We describe the use of peripheral venoarterial extracorporeal membrane oxygenation as a short-term treatment of right heart failure after HeartWare LVAD implantation.
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Increasing incidence of end-stage heart failure and limited availability of donor organs have led to longer waiting times for cardiac transplantation and subsequently increasing mortality. Ventricular assist device therapy is fast becoming an accepted alternative treatment to treat end-stage heart failure and is being implemented as a bridge to decision, bridge to myocardial recovery, bridge to heart transplantation or as a destination therapy. LVADs not only enable hemodynamic stabilization and recovery of secondary organ failure in severely ill patients, but have also been shown to reduce pulmonary vascular resistance in nontransplantable candidates. Technology of ventricular assist devices has evolved over several decades of time and generations of devices. The HVAD(®) Pump (HeartWare International, Inc., MA, USA) is a third-generation, miniaturized, continuous-flow ventricular assist device. Due to its miniaturized housing and intrapericardial placing, it can be used proficiently to support the right ventricle and has also demonstrated great utility in minimally invasive and off-pump implantation, exchange and explantation. It is favored for similar reasons in adolescents and in heart failure due to complex congenital heart disease. The purpose of this article is to review the clinical use of HeartWare(®) Ventricular Assist System (HeartWare System; HeartWare International, Inc.) with different strategies pertaining to its advantages and adverse events in comparison with contemporary devices.
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Heart transplantation remains the gold standard for long-term cardiac replacement, but a shortage of donor organs will always limit this option. For both transplant-eligible and noneligible patients, advances in mechanical circulatory support have revolutionized the options for the management of end-stage heart failure, and this technology continues to bring us closer to a true alternative to heart transplantation. This review provides a perspective on the past, present and future of mechanical circulatory support and addresses the changes in technology, patient selection and management strategies needed to have this therapy fully embraced by the heart failure community, and perhaps replace heart transplantation either as the therapy of choice or as a strategy by which to delay transplantation in younger patients.
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To review left ventricular assist device physiology, initial postoperative management, common complications, trouble shooting and management of hypotension, and other common ICU problems. Narrative review of relevant medical literature. Left ventricular assist devices prolong the lives of patients with end-stage heart failure, and their use is increasing. Continuous-flow left ventricular assist devices have replaced first-generation pulsatile devices. These patients present unique management concerns. In the immediate postimplant period, care must be taken to support the unassisted right ventricle. Invasive monitors for blood pressure, pulmonary artery catheterization, and echocardiography are essential to optimize left ventricular assist device settings and cardiac performance. Anticoagulation is necessary to prevent devastating thrombotic and embolic complications, but bleeding is a major source of morbidity due to inherent bleeding diatheses and prescribed anticoagulants. Infection of the device can be life threatening, and all infections must be aggressively treated to avoid seeding the device. Patients are at risk of ventricular arrhythmias because of their underlying disease, as well as the placement and position of the inflow cannula. Aortic valve stenosis and insufficiency develop over time and can lead to thrombosis or heart failure. Cardiopulmonary resuscitation with chest compressions must be performed with care or not at all due to risk of dislodging the device. Intensivists are increasingly likely to encounter patients requiring mechanical circulatory support with left ventricular assist devices at various points in the trajectory of their disease, from the immediate postimplant period to subsequent admissions for complications, and at end of life. A basic understanding of left ventricular assist device physiology is essential to the safe and effective care of these patients.
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Exchange of the HeartWare HVAD made necessary by thrombosis or cable damage is rare, but it is a complex procedure associated with morbidity. Less invasive exchange procedures may contribute to faster postoperative recovery and early mobilization. Between September 2009 and April 2012, 225 patients (median age 55.4 years, range 7-82 years, 40 of them women) were supported with the HeartWare HVAD at our institution. Cumulative follow-up in all 225 patients was 151.9 patient/years. In six patients, early pump thrombosis (<30 days) requiring pump exchange occurred after a median time of 7 (2-9) days. In six patients, late pump thrombosis requiring pump exchange occurred after a median of 380 (84-705) days. The overall incidence was 5.3% with 0.079 thromboses per year. In two instances of accidental cable damage as a result of massive external mechanical impact, pump exchange was necessary. We describe a safe and less invasive technique for the explantation and exchange of the HeartWare HVAD through a left thoracotomy. Pump thrombosis of the HeartWare HVAD is a very rare condition caused mostly by new onset of heparin-induced thrombocytopenia type II, mismanagement of anticoagulation, or hypercoagulability in the case of severe sepsis. Since the introduction of the sintered inflow cannula no early thrombosis has occurred. Pump exchange in the case of hemolysis should not be delayed. The cable of the HeartWare HVAD is very reliable and breaks only after excessive external impact. A minimally invasive approach for pump exchange on cardiopulmonary bypass for pump thrombosis and off-pump for cable damage or pump explantation is recommended.
Article
Continuous-flow left ventricular assist devices (CF-LVADs) are increasingly used to support patients with advanced heart failure (HF). Device thrombosis is a serious complication of CF-LVADs, but its precise prevalence and etiology remains uncertain. Root-cause analysis was performed in all cases with device thrombosis confirmed upon explant among patients implanted with a HeartMate II (HM II) from January 1, 2009 to November 15, 2012. Cannula position and bend relief integrity were assessed and charts were reviewed with particular attention to anti-coagulation and infection profiles. Nineteen of 177 patients (11%) were found to have device thrombosis of various etiologies after a mean of 351 ± 311 days, representing 0.12 event/patient-year. Of the 5 mechanically induced thromboses, proximate etiology was severely abnormal inflow cannula position in 3 patients and bend relief disconnect with deformed outflow graft in 2 patients. One patient had a hypercoagulable disorder with prior arterial embolism. In the remaining 13 patients (age 61 ± 14 years, 77% male, 69% Caucasian), "non-mechanical" device thrombosis occurred after 357 ± 383 days; INR at the time of diagnosis was 1.81 (1.62 to 2.07); and mean device speed was 8,855 ± 359 rpm. Five of 13 patients (38%) had an infection during the month leading up to device thrombosis. Of note, lactate dehydrogenase (LDH) was already elevated at the time of discharge in patients who would later develop non-mechanical device thrombosis (423 [354 to 766] vs 352 [272 to 373] U/liter, p < 0.01). Device thrombosis is a multifactorial phenomenon, and differentiation of mechanical and non-mechanical causes is an essential step for individual diagnosis and treatment plans. Larger studies excluding patients with obvious mechanical etiology are needed to investigate biologic and/or management-related risk factors for device thrombosis. Our findings suggest that LDH may be an early risk marker. Due to the difficulty in treating late-stage device thrombosis, we suggest early use of simple tests to rule out both causes of thrombosis, such as X-rays and closer LDH monitoring (bi-weekly).
Article
Ventricular assist device (VAD) thrombosis, though uncommon, is a well-known complication. A HeartWare VAD implanted 2 years ago in a middle-aged man stopped because of thrombosis in the VAD. Because the patient's left ventricular function was recovered by the time of intervention, only the outflow graft was isolated and cut, leaving the pump in place.
Article
Left ventricular assist device thrombosis is a detrimental complication that, if not properly diagnosed and treated, can lead to low output syndrome and death. When ongoing thrombus formation is caused by inappropriate anticoagulation, timely identification is possible, and could perhaps be the key to successful treatment.
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Hemodynamic support with continuous-flow left ventricular assist device (CF-LVAD) therapy has proven a reliable treatment for advanced heart failure. Although modern LVADs are highly durable, device failure and infection can be resolved with surgical exchange of pump components. In this study, we investigated the incidence and outcomes of LVAD exchange with the HeartMate II and HeartWare HVAD. Data were obtained from 677 patients who underwent CF-LVAD implantation between 2005 and 2016. Patients who underwent a device exchanged were included. The primary outcomes were length of hospital stay and mortality. Of the 677 patients included in this study, 72 (10.6%) required LVAD exchange. Thirty-day and 1-year mortality rates were comparable to primary LVAD implantation: 4.3% vs. 3.49%, p = 0.727 and 20.3% vs. 20.7%, p = 0.989, respectively. Thirty-one patients (4.5%) underwent exchange with ongoing infection. Kaplan-Meier analysis indicated significant differences in survival between groups based on indication for exchange. Patients who underwent exchange after more than 150 days of active infection suffered worse postexchange survival than those who underwent exchanged earlier (P = 0.007). While exchange was required only in 10.6% of patients undergoing LVAD implantation, our results show device exchange may be executed safely and effectively, with long-term outcomes similar to primary LVAD implantation. The indication for device exchange impacts postexchange outcomes, and those exchanged with LVAD infection tend to fare worse than those exchanged for device malfunction or thrombus. Patients who are exchanged with active infection have better postoperative survival if the exchange is performed expeditiously after medical management has failed.
Article
Dual rotary left ventricular assist devices (LVADs) have been used clinically to support patients with biventricular failure. However, due to the lower vascular resistance in the pulmonary circulation compared with its systemic counterpart, excessively high pulmonary flow rates are expected if the right ventricular assist device (RVAD) is operated at its design LVAD speed. Three possible approaches are available to match the LVAD to the pulmonary circulation: operating the RVAD at a lower speed than the LVAD (mode 1), operating both pumps at their design speeds (mode 2) while relying on the cardiovascular system to adapt, and operating both pumps at their design speeds while restricting the diameter of the RVAD outflow graft (mode 3). In this study, each mode was characterized using in vitro and in vivo models of biventricular heart failure supported with two VentrAssist LVADs. The effect of each mode on arterial and atrial pressures and flow rates for low, medium, and high vascular resistances and three different contractility levels were evaluated. The amount of speed/diameter adjustment required to accommodate elevated pulmonary vascular resistance (PVR) during support with mode 3 was then investigated. Mode 1 required relatively low systemic vascular resistance to achieve arterial pressures less than 100 mm Hg in vitro, resulting in flow rates greater than 6 L/min. Mode 2 resulted in left atrial pressures above 25 mm Hg, unless left heart contractility was near-normal. In vitro, mode 3 resulted in expected arterial pressures and flow rates with an RVAD outflow diameter of 6.5 mm. In contrast, all modes were achievable in vivo, primarily due to higher RVAD outflow graft resistance (more than 500 dyn·s/cm(5) ), caused by longer cannula. Flow rates could be maintained during instances of elevated PVR by increasing the RVAD speed or expanding the outflow graft diameter using an externally applied variable graft occlusion device. In conclusion, suitable hemodynamics could be produced by either restricting or not restricting the right outflow graft diameter; however, the latter required an operation of the RVAD at lower than design speed. Adjustments in outflow restriction and/or RVAD speed are recommended to accommodate varying PVR.
Article
Biventricular support with dual rotary ventricular assist devices (VADs) has been implemented clinically with restriction of the right VAD (RVAD) outflow cannula to artificially increase afterload and, therefore, operate within recommended design speed ranges. However, the low preload and high afterload sensitivity of these devices increase the susceptibility of suction events. Active control systems are prone to sensor drift or inaccurate inferred (sensor-less) data, therefore an alternative solution may be of benefit. This study presents the in vitro evaluation of a compliant outflow cannula designed to passively decrease the afterload sensitivity of rotary RVADs and minimize left-sided suction events. A one-way fluid-structure interaction model was initially used to produce a design with suitable flow dynamics and radial deformation. The resultant geometry was cast with different initial cross-sectional restrictions and concentrations of a softening diluent before evaluation in a mock circulation loop. Pulmonary vascular resistance (PVR) was increased from 50 dyne s/cm5 until left-sided suction events occurred with each compliant cannula and a rigid, 4.5 mm diameter outflow cannula for comparison. Early suction events (PVR ∼ 300 dyne s/cm5) were observed with the rigid outflow cannula. Addition of the compliant section with an initial 3 mm diameter restriction and 10% diluent expanded the outflow restriction as PVR increased, thus increasing RVAD flow rate and preventing left-sided suction events at PVR levels beyond 1000 dyne s/cm5. Therefore, the compliant, restricted outflow cannula provided a passive control system to assist in the prevention of suction events with rotary biventricular support while maintaining pump speeds within normal ranges of operation.
Article
Continuous-flow left ventricular assist devices reduce short-term mortality and improve quality of life in patients with end-stage heart failure. Unfortunately, device-related complications remain common, with many patients experiencing adverse events within the first year. New literature suggests that rates of device-related thrombosis may be increasing since 2011, which is particularly troublesome given that this pathology can result in a disabling stroke, organ damage, and death. In 2013, a group of practitioners in the field of mechanical circulatory support published a treatment algorithm based on their expert opinion. However, a comprehensive review of the pharmacotherapy of this condition is lacking. A search of the literature revealed 20 separate publications of case reports or case series describing outcomes associated with the use of drug therapy for suspected pump thrombosis. Each of these experiences was limited by small sample size, nonrandomized treatment allocation, and nonstandardized medication dosing. Data describing the outcomes of surgical versus medical management of device thrombosis are also sparse, with only three published reports identified. Based on the review of this limited literature, surgical management appears to be the preferred treatment modality, especially in those with organ hypoperfusion or hemodynamic instability. In patients ineligible for surgery, pharmacotherapy options remain limited. Use of all drug classes described in the literature for the HeartMate II device-fibrinolytics, glycoprotein IIb/IIIa inhibitors, and direct thrombin inhibitors-was hindered by either marginal efficacy or bleeding. Based on historical experience with unfractionated heparin in patients under HeartMate II support, we recommend this agent as a possible option for those with suspected pump thrombosis in lieu of surgical device exchange. For the HeartWare HVAD, limited data suggest that direct intraventricular administration of alteplase may be an acceptable treatment alternative. Additional research is clearly needed to further delineate the role of pharmacotherapy and to identify the optimal agent for managing this potentially life-threatening condition.
Article
Endoventricular thrombolytic procedure (ETP) has been used to treat continuous-flow left ventricle assist device (CF-LVAD) thrombosis. The study aims to investigate the occurrence of complications after ETP. Data were retrospectively reviewed and analyzed in a series of patients who underwent CF-LVAD followed by ETP. Since November 2010, 20 patients underwent HeartWare CF-LVAD implantation at our institute. Four patients (20%) developed pump thrombosis and underwent a total of nine ETPs with tissue plasminogen activator infused into the left ventricle. The mean age was 60.2 ± 9 years. ETP was performed via either the femoral (n = 6) or radial artery (n = 3). Five ETPs (55.5%) were complicated by left and right radial artery occlusion, two by groin hematomas, and one by femoral artery false aneurysm. ETP carries a strong risk of vascular access complications that, in CF-LVAD patients, may add to the already complex clinical profile and economic burden; thus, a less invasive treatment is advisable whenever required.
Chapter
Cardiovascular disease is the leading cause of global morbidity. Chronic ischemic heart disease, acute heart failure, and myocardial infarction are among the primary causes of mortality in Europe (45% of all deaths), the United States of America (34.3%), and worldwide (45% of noncommunicable diseases). Different strategies can be planned for the treatment of heart disease according to the severity, cause, and course of heart failure. It includes adjusting patients’ lifestyle, medication, and surgical treatment. But for patients with end-stage heart failure waiting for heart transplantation, the number of donated hearts is usually insufficient. Therefore, the auxiliary equipment of ventricular implantation becomes very important. Because it can provide different treatment options for patients with heart failure from excessive to recovery, decision, transplantation, or ultimate treatment. According to the seventh INTERMACS data showed that more than 13,000 patients received left ventricular support from the United States in 2014, of which 955 received pulsatile flow LVADs and 12,030 continuous flow LVADs. This chapter provides an overview of the current implantable rotating left ventricular assist device (LVAD), patient selection, surgical overview, and postoperative management strategies.
Article
Articular cartilage has a limited capacity for spontaneous repair, and an effective method to repair damaged articular cartilage has not yet been established. The purpose of this study was to evaluate the effect of transplantation of porous hydroxyapatite collagen (HAp/Col) impregnated with bone morphogenetic protein-2 (BMP-2). To evaluate the characteristics of porous HAp/Col as a drug delivery carrier of recombinant human BMP-2 (rhBMP-2), the rhBMP-2 adsorption capacity and release kinetics of porous HAp/Col were analyzed. Porous HAp/Col impregnated with different amounts of rhBMP-2 (0, 5, and 25 μg) was implanted into osteochondral defects generated in the patellar groove of Japanese white rabbits to evaluate the effect on osteochondral defect regeneration. At 3, 6, 12, and 24 weeks after operation, samples were harvested and subjected to micro-computed tomography analysis and histological evaluation of articular cartilage and subchondral bone repair. The adsorption capacity was 329.4 μg of rhBMP-2 per cm(3) of porous HAp/Col. Although 36% of rhBMP-2 was released within 24 h, more than 50% of the rhBMP-2 was retained in the porous HAp/Col through the course of the experiment. Defects treated with 5 μg of rhBMP-2 showed the most extensive subchondral bone repair and the highest histological regeneration score, and differences against the untreated defect group were significant. The histological regeneration score of defects treated with 25 μg of rhBMP-2 increased up to 6 weeks after implantation, but then decreased. Porous HAp/Col, therefore, is an appropriate carrier for rhBMP-2. Implantation of porous HAp/Col impregnated with rhBMP-2 is effective for rigid subchondral bone repair, which is important for the repair of the smooth articular surface. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
Article
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As a left ventricular assist device is designed to pump against the systemic vascular resistance (SVR), pulmonary congestion may occur when using such device for right ventricular support. The present study evaluates the efficacy of using a fixed right outflow banding in patients receiving biventricular assist device support under various circulatory conditions, including variations in the SVR, pulmonary vascular resistance (PVR), total blood volume (BV), as well as ventricular contractility. Effect of speed variation on the hemodynamics was also evaluated at varying degrees of PVR. Pulmonary congestion was observed at high SVR and BV. A reduction in right ventricular assist device (RVAD) speed was required to restore pulmonary pressures. Meanwhile, at a high PVR, the risk of ventricular suction was prevalent during systemic hypotension due to low SVR and BV. This could be compensated by increasing RVAD speed. Isolated right heart recovery may aggravate pulmonary congestion, as the failing left ventricle cannot accommodate the resultant increase in the right-sided flow. Compared to partial assistance, the sensitivity of the hemodynamics to changes in VAD speed increased during full assistance. In conclusion, our results demonstrated that the introduction of a banding graft with a 5 mm diameter guaranteed sufficient reserve of the pump speed spectrum for the regulation of acceptable hemodynamics over different clinical scenarios, except under critical conditions where drug administration or volume management is required.
Article
Objectives: The study sought to characterize patterns in the HeartWare (HeartWare Inc., Framingham, Massachusetts) ventricular assist device (HVAD) log files associated with successful medical treatment of device thrombosis. Background: Device thrombosis is a serious adverse event for mechanical circulatory support devices and is often preceded by increased power consumption. Log files of the pump power are easily accessible on the bedside monitor of HVAD patients and may allow early diagnosis of device thrombosis. Furthermore, analysis of the log files may be able to predict the success rate of thrombolysis or the need for pump exchange. Methods: The log files of 15 ADVANCE trial patients (algorithm derivation cohort) with 16 pump thrombus events treated with tissue plasminogen activator (tPA) were assessed for changes in the absolute and rate of increase in power consumption. Successful thrombolysis was defined as a clinical resolution of pump thrombus including normalization of power consumption and improvement in biochemical markers of hemolysis. Significant differences in log file patterns between successful and unsuccessful thrombolysis treatments were verified in 43 patients with 53 pump thrombus events implanted outside of clinical trials (validation cohort). Results: The overall success rate of tPA therapy was 57%. Successful treatments had significantly lower measures of percent of expected power (130.9% vs. 196.1%, p = 0.016) and rate of increase in power (0.61 vs. 2.87, p < 0.0001). Medical therapy was successful in 77.7% of the algorithm development cohort and 81.3% of the validation cohort when the rate of power increase and percent of expected power values were <1.25% and 200%, respectively. Conclusions: Log file parameters can potentially predict the likelihood of successful tPA treatments and if validated prospectively, could substantially alter the approach to thrombus management.
Article
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A growing number of patients are undergoing prolonged management of advanced heart failure with the use of continuous flow left ventricular assist devices (LVADs). Subsequently, an increasing number of patients are presenting with complications associated with these devices. Based on an analysis of three major LVAD institutions, the number of patients developing LVAD pump thrombosis may be much higher than originally projected. [1],[2] The management of this highly feared complication continues to be challenging, as the population of LVAD patients is very heterogeneous and heavily burdened with comorbidities. The standard protocol of increasing anticoagulation may fail to achieve successful resolution of thrombus. Difficulty and poor prognosis may make reoperation less than desirable. Here, we present a case of successful thrombolysis following intravenous administration of tissue plasminogen activator in the Intensive Care Unit setting.
Chapter
Advanced heart failure (HF) and cardiogenic shock are heterogeneous entities. The Interagency Registry for Mechanical Assisted Circulatory Support (INTERMACS) has developed profile levels to better characterize clinical status. Beyond intra-aortic balloon pump (IABP) counterpulsation therapy and venoarterial extracorporeal membrane oxygenation (ECMO), various options have emerged for cardiac assist devices. Advanced HF support alternatives include percutaneous assist devices, short-term devices, and long-term, implantable ventricular assist devices (VADs). This chapter discusses the principles of application for these devices. The gold standard, however, for end-stage heart disease remains cardiac transplantation. With an ever-growing deficit in available donors compared to required organs, assist-device-based bridging strategies and strategic use of these grafts are paramount. Additionally, an approach to mechanical circulatory support (MCS) implantation stratified by INTERMACS profile levels (1–7), based on clinical goals and the required duration of assistance, is suggested.
Article
Background: Continuous flow left ventricular assistance devices (CF-LVADs) have revolutionized the treatment of advanced heart failure. Pump replacement for thrombosis is a high-risk procedure with a high perioperative mortality rate with possible recurrence. We aim to summarize our experience using a conservative approach with medical therapy. Methods: We retrospectively reviewed records of patients who experienced pump thrombosis after LVAD implantation with HeartWare HVAD at our institution, from November 2010 to March 2016. Device thrombosis (DT) was divided into suspected (SDT) and confirmed (CDT). A conservative approach using thrombolysis and heparin was used in all patients. Results: A total of 32 HeartWare HVAD pumps were implanted. Mean age was 59 ± 10 years and the mean time on mechanical support was 19.29 months (±14.06). Pump thrombosis occurred in 7 patients (0.14 patients/year) after a mean time of 733 (231-1,606) days after LVAD implantation. Three out of 7 cases had thrombosis recurrence (43%). Overall 19 episodes were recorded (0.38 event per patient/year). Eighteen out of 19 thrombolytic treatments were successful (94.7%). No patient required LVAD replacement or transfusion of blood products. There was no significant difference in terms of survival between patients who experienced thrombotic events and patients who did not. No major complications related to thrombolysis were recorded. Conclusions: Systemic thrombolysis plus heparin was an excellent therapeutic option. Early intervention in clinically stable patients without signs of heart failure but with indirect signs of device thrombosis has led to better outcomes.
Article
Aim Pump thrombosis (PT) is a detrimental complication of left ventricular assist device (LVAD) therapy. There is no consensus on optimal PT treatment. The aim of this study was to present a treatment strategy for patients with PT. Method The hospital records of patients who underwent isolated LVAD implantation between May 2013 and October 2018 were retrospectively evaluated. Pump thrombosis was suspected in the setting of impaired flow/power parameters and haemolysis. Protocols for the management of suspected PT varied by patient presentation. Parameters that increased the PT risk were investigated by dividing the patients into two groups according to the presence of PT. Preoperative and operative data were analysed. Results Pump thrombosis was observed in 20 of 81 patients. All patients with PT presented elevated lactate dehydrogenase levels and higher power and/or low-/high-flow alarm at admission. All patients were treated initially with intravenous unfractionated heparin infusion; three patients did not require further treatment, one patient died due to sudden cardiac arrest, and three patients underwent urgent surgery for LVAD exchange. Thirteen (13) patients received tissue plasminogen activator infusion; eight were discharged without any signs of thrombosis, and three were bridged to transplant. One (1) major bleeding event leading to death was observed. Freedom from second PT was found in 91% cases at 6 months and in 68.2% at 1 year. We found that a larger left ventricle and the type of pump determined the risk of PT. Conclusions Low-dose thrombolytic therapy should be considered as a feasible treatment option for patients with PT.
Article
Thrombembolic complicationsarecommoninpatientswith mechanical circulatorysupportandrequireurgenttherapeutic action. Theauthors' case showsthatintravenousthrombolysis with recombinantorurokinase-typeplasminogenactivatorcan be consideredwhenasurgicalpumpexchangeisnotanoption. The final outcomeintheirpatienthighlightsthe fine line between theriskofthrombosisandhemorrhagiccomplications in VADpatients.FurthertechnicaldevelopmentoftheVADas well asbetterunderstandingoftheinteractionbetweenthe blood coagulationsystemandtheartificial surfacesofthepump hopefully willallowforpreventiveandtherapeuticmeasures, which areeffectiveandsafe.
Article
Tenecteplase is a triple combination mutant variant of alteplase with high fibrin specificity and resistance to plasminogen activator inhibitor-1. The reduced rate of systemic clearance of the drug relative to alteplase allows tenecteplase to be given by rapid bolus injection to patients with acute myocardial infarction (AMI) with ST segment elevation. The efficacy of tenecteplase in AMI has been demonstrated in a phase I dose-ranging trial [Thrombolysis in Myocardial Infarction (TIMI) 10A], a nonblind phase II comparison with alteplase (TIMI 10B), and a randomized double-blind phase III comparison with alteplase in 16 949 patients [the second Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) trial]. Patients also received aspirin and intravenous heparin in all trials. In TIMI 10A and 10B, TIMI grade 3 coronary flow was achieved after 90 minutes in 54.3 to 65.8% of patients receiving tenecteplase 30, 40 or 50mg; in TIMI 10B, grade 3 flow was reported in 62.7% patients receiving alteplase (≤100mg by front-loaded infusion over 90 minutes). Thirty-day mortality was similar with bodyweight-adjusted intravenous bolus doses of tenecteplase 30 to 50mg and front-loaded 90-minute infusion of alteplase in ASSENT-2 (approximately 6.2%). Rates of reinfarction and cardiogenic shock were also similar between groups, although mortality was reduced with tenecteplase in patients receiving treatment more than 4 hours after onset of symptoms (7 vs 9.2%; p = 0.018). Preliminary data show maintenance of the similarity between groups over 1 year (approximate 10.2% mortality in both groups), with loss of statistical significance between groups in patients treated late. ASSENT-2 showed the risks of intracranial hemorrhage (0.93%) and stroke (all causes) [1.78%] with tenecteplase to be similar to those with alteplase (0.94 and 1.66%, respectively). The rate of noncerebral bleeding was lower with tenecteplase than with alteplase (26.43 vs 28.95%; p = 0.0003). No causal link has been demonstrated between tenecteplase and allergic reactions in patients. Conclusions: Bolus tenecteplase is an effective thrombolytic agent, suitable for first-line use in patients with AMI with ST segment elevation. Results to date show overall efficacy and tolerability profiles similar to those of alteplase, with comparable mortality after 1 year’s follow-up. The apparent advantages of tenecteplase (reduced mortality in patients receiving late treatment and reduced incidence of noncerebral bleeding complications) in ASSENT-2 are of interest and merit further attention. The full implications of the availability of bolus administration and its potential clinical advantages over the currently widely used infusion regimens, together with the effect on outcomes of addition of tenecteplase to platelet glycoprotein IIb/IIIa inhibition, are currently under investigation. Pharmacologic Overview Tenecteplase acts on the physiologic fibrinolytic system in a manner similar to tissue plasminogen activator (t-PA). Studies in animals have shown earlier and more sustained femoral artery recanalization with tenecteplase than with alteplase (the recombinant form of natural t-PA) after artificially induced thrombus formation. Studies in a rabbit model showed tenecteplase to induce 50% lysis of whole blood clots 3 times faster than natural t-PA (mean 35 vs 120 minutes) when either drug was given at the same dose (0.18 mg/kg). Tenecteplase was also shown to have fibrinolytic activity and fibrin binding capacity similar to those of natural t-PA in plasma-based clots, but with fibrin specificity and resistance to plasminogen activator inhibitor-1 enhanced 14- and 80-fold, respectively. The fibrin specificity and plasminogen-conserving properties relative to alteplase of tenecteplase in circulating blood in humans have been shown in a phase II comparison of intravenous bolus doses of 30, 40 or 50mg with a front-loaded 90-minute infusion of alteplase of up to 100mg. Median levels of circulating plasminogen were reduced from baseline by 10 to 15% in tenecteplase recipients, and by 50% in patients receiving alteplase, over the first 6 hours. Consumption of α2-antiplasmin and increases in median levels of plasmin/α2-antiplasmin complex in plasma in alteplase recipients were 4 to 5 times greater than those seen with any dose of tenecteplase. Over the first 6 hours, circulating levels of fibrinogen were reduced from baseline by a median 5 to 10% in patients receiving tenecteplase and by 40% in those receiving alteplase. Available data indicate that tenecteplase lacks the procoagulant properties seen with other thrombolytic drugs such as streptokinase or (to a lesser extent) alteplase. Tenecteplase has an initial volume of distribution similar to that of plasma. Extravascular distribution is suggested by an increased volume of distribution at steady state relative to the initial volume of distribution: data obtained in rats indicate the liver to be the organ chiefly involved. Tenecteplase is eliminated from plasma in a biphasic fashion, with a mean initial half-life (t½) of approximately 22 minutes and a mean terminal elimination t½ of 1.5 to 2.2 hours (approximately 90 to 130 minutes). The initial (α) phase is dominant, accounting for a mean 66 to 75% of the total area under the plasma drug concentration versus time curve across the dose range of 30 to 50mg. Plasma clearance is independent of dose, and is approximately 4 times slower than with alteplase. Therapeutic Efficacy in Acute Myocardial Infarction The therapeutic efficacy of tenecteplase in AMI has been assessed in 3 major studies. The first (TIMI 10A) was a phase I dose-ranging trial, the second (TIMI 10B) was a nonblind phase II comparison of fixed doses of intravenous bolus tenecteplase with a front-loaded infusion of alteplase, and the third (ASSENT-2) was a phase III comparison of bodyweight-adjusted bolus tenecteplase with infused alteplase. Patients underwent thrombolysis within 12 hours of onset of symptoms in TIMI 10A and 10B, and within 6 hours in ASSENT-2. TIMI 10A and 10B. These studies focused on re-establishment of coronary blood flow as reflected by TIMI gradings and frame counts, whereas 30-day mortality was the primary end-point in ASSENT-2. Patients in all trials received aspirin 150 to 325mg daily, with intravenous heparin for 48 to 72 hours. In TIMI 10A, 113 patients received single bolus doses of tenecteplase ranging from 5 to 50mg; TIMI grade 3 flow was achieved after 90 minutes by 57 to 64% of patients receiving tenecteplase 30 to 50mg (p = 0.032 vs lower doses). In TIMI 10B, which involved an evaluable cohort of 837 patients, TIMI grade 3 flow was reported after 90 minutes in 54.3 to 65.8% of patients receiving tenecteplase 30, 40 or 50mg, and in 62.7% of alteplase recipients (15mg intravenous bolus, then infusion of 0.75 mg/kg to a maximum dose of 50mg over 30 minutes, and a subsequent infusion of 0.5 mg/kg to a maximum of 35mg over the next 60 minutes). TIMI frame counts were concordant with flow gradings in both studies. The 30-day mortality rate in TIMI 10A was 3.5% across all treatment groups, with reinfarction reported in 4.4% of patients. In TIMI 10B, overall rates of mortality and reinfarction at 30 days were 4.9 and 5.4%, respectively, with no significant differences between any of the treatment groups. ASSENT-2. This was a large, randomized double-blind study carried out in 29 countries in an intention- to-treat population of 16 949 patients. Tenecteplase was given on a bodyweight-adjusted basis as intravenous bolus doses ranging from 30 to 50mg (n = 8461), whereas alteplase was given as a front-loaded infusion as in TIMI 10B. Heparin was given as a 4000U bolus plus infusion of 800 U/h for patients ≤67kg, and as a 5000U bolus plus 1000 U/h in patients >67kg, with a target activated partial thromboplastin time of 50 to 75 seconds for 48 to 72 hours. Kaplan-Meier survival curves for tenecteplase and alteplase were superimposable, and 30-day mortality rates were similar in both groups (6.179% with tenecteplase and 6.151% with alteplase). This similarity persisted in analyses carried out in prespecified patient subgroups, although the mortality rate at 30 days was reduced with tenecteplase in patients receiving treatment more than 4 hours after AMI (7 vs 9.2%; p = 0.018). Thirty-day reinfarction rates were 4.1 and 3.8% with tenecteplase and alteplase, respectively; corresponding rates of cardiogenic shock were 3.9 and 4%. Preliminary 1-year follow-up data from 14 203 patients, 12 311 of whom remained alive, show mortality rates of 10.15 and 10.23% in patients receiving tenecteplase and alteplase, respectively (p = 0.87 between groups). Corresponding rates of mortality of 12.1 and 14.4% were reported in patients receiving treatment more than 4 hours after onset of symptoms; the statistical significance between groups noted after 30 days was not apparent after 1 year, however (p = 0.069). Tolerability The risks of intracranial hemorrhage and stroke from all causes (the major adverse events of concern in patients receiving thrombolytic agents) with tenecteplase appear similar on the basis of current data to those with alteplase. In the ASSENT-2 study, there were no significant differences between bodyweight-adjusted bolus doses of tenecteplase and front-loaded infusion of alteplase in incidences of intracranial hemorrhage (0.93 vs 0.94%), stroke (all causes; 1.78 vs 1.66%), ischemic stroke (0.72 vs 0.64%) and hemorrhagic conversion (0.07 vs 0.09%). However, the rate of noncerebral bleeding complications was significantly lower in the tenecteplase group (26.43 vs 28.95%; p = 0.0003). The phase II first Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-1) trial, which was set up to assess the tolerability of tenecteplase in 3235 patients with AMI, showed severe bleeding in 1.6% of patients across bolus doses of 30 to 50mg. The overall rate of stroke at 30 days was 1.5%. The incidence of intracranial hemorrhage was 0.77%. Allergic reactions have been reported only rarely (<1% of patients) in recipients of tenecteplase, although no causal link between the drug and these effects has been shown. As arrhythmia associated with reperfusion is sometimes reported in patients receiving thrombolytic therapy, it is recommended that appropriate counter-measures be available in centers in which tenecteplase is in use. Dosage and Administration Tenecteplase should be administered as a single bodyweight-adjusted intravenous bolus injection of 30 to 50mg over 5 seconds as soon as possible after the onset of symptoms of AMI. The drug is presented in 50mg vials as a lyophilized powder for dissolution in water for injections and immediate use. The syringe supplied is designed primarily for use with needleless intravenous systems, although attachment to a needle is possible if necessary. Tenecteplase should not be given to patients with any of the following: active internal bleeding; a history of cerebrovascular accident; a history of intracranial or intraspinal surgery within the preceding 2 months; intracranial neoplasm, arteriovenous malformation or aneurysm; known bleeding diathesis; severe uncontrolled hypertension. Although sustained antibody formation has not been reported in patients receiving a single dose of tenecteplase, readministration should be undertaken with caution. Studies of the use of tenecteplase in pregnant or nursing women have not been carried out, and careful risk-benefit assessment is therefore required when contemplating the use of the drug in these patients.
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The aim of this study was to conduct an initial clinical evaluation of the new HeartWare Ventricular Assist System (HeartWare, Inc., Framingham, Massachusetts) in a multicenter, prospective, nonrandomized single-arm clinical trial. Heart failure is a worldwide epidemic. The effectiveness of heart transplantation and medical therapy is limited, resulting in the emergence of mechanical circulatory support as a primary treatment for end-stage heart disease. Left ventricular assist devices that use rotary pumps are small and durable, which might reduce morbidity and mortality during support. Fifty heart transplant candidates with New York Heart Association functional class IV symptoms were supported at 5 international centers by the HeartWare System for 180 days, until heart transplant, myocardial recovery and device explant, or death. Patients who continue to be supported have been followed for a minimum of 2 years. Of the 50 patients, 20 (40%) received transplants, 4 (8%) had the pump explanted after myocardial recovery, and 17 (34%) continue support at 2 years. Nine (18%) patients died during support from sepsis (n = 3), multiple organ failure (n = 3), or hemorrhagic stroke (n = 3). The actual survival at 6, 12, and 24 months was 90%, 84%, and 79%, respectively. In the survivors, measures of quality of life showed a significant improvement over baseline values. Significant improvements were found for recognition memory at 3 months after implant (p = 0.006). The most frequent adverse events were infection and bleeding. Patients with end-stage heart failure can be safely and effectively supported by the HeartWare Ventricular Assist System with improved quality of life and neurocognitive function.
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A woman presented for evaluation of new-onset left arm edema after failed laser-assisted pacemaker lead extraction. Initial workup demonstrated a left subclavian artery to vein arteriovenous fistula (AVF). She underwent repair of the AVF with placement of a covered stent in the subclavian artery, however, her symptoms did not completely resolve. Investigation revealed a left common carotid artery to left innominate vein AVF, which was repaired by deploying a covered stent retrograde into the left common carotid artery. Her symptoms subsequently resolved. Multiple iatrogenic AVF can be repaired endovascularly, however, a high degree of suspicion for multiple injuries should be maintained.
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The left internal mammary artery was severed and an arteriovenous fistula created during extraction of pacemaker leads with a laser sheath.
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Transvenous pacemaker lead extraction has become a commonly performed procedure that is associated with a small but significant risk. We report two cases where lead extraction was complicated by arteriovenous fistulae between branches of the aortic arch and the left brachiocephalic vein. Presenting signs and symptoms included severe chest or back pain, persistent or copious bleeding from the venous puncture site, unexplained hypotension or anemia, superior vena cava syndrome, and signs of central venous hypertension or acute heart failure. One patient whose injury was not recognized immediately and who did not undergo repair died rapidly, whereas the other patient who was diagnosed quickly underwent successful repair. Immediate diagnosis with arteriography and rapid intervention with surgery or percutaneous techniques are indicated and may prevent mortality.
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The latest generation of left ventricular assist devices consists of nonpulsatile impeller pumps. In these small pumps, thrombus formation inside the device does not lead to thromboembolic end-organ dysfunction but may dramatically impair pump flow. We report on our experience with thrombus-related pump dysfunctions of the MicroMed DeBakey left ventricular assist device and its treatment. Eight of 22 patients with a MicroMed DeBakey VAD presented with a critically reduced pump flow. In 7 cases, an increased power demand indicative of progressive thrombus formation associated with the device was evident, whereas 1 case presented with thrombus formation within the inflow conduit associated with a very low power demand. Brief spontaneously resolving pump stops had been noted in 6 patients. All 8 patients were treated with 100 mg of recombinant tissue plasminogen activator (rt-PA), administered via an IV line. Rt-PA lysis led to an increase of pump flow along with a reduction of power demand within a short time in all patients. No severe bleeding complications occurred. However, 4 patients experienced transient epistaxis. All patients could be discharged from intensive care immediately after discontinuation of thrombolytic therapy. Rt-PA lysis is a very effective tool for thrombus-related pump dysfunction in patients with impeller pumps, which renders emergency surgical exchange unnecessary in most cases.
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Unlabelled: Tenecteplase is a triple combination mutant variant of alteplase with high fibrin specificity and resistance to plasminogen activator inhibitor-1. The reduced rate of systemic clearance of the drug relative to alteplase allows tenecteplase to be given by rapid bolus injection to patients with acute myocardial infarction (AMI) with ST segment elevation. The efficacy of tenecteplase in AMI has been demonstrated in a phase I dose-ranging trial [Thrombolysis in Myocardial Infarction (TIMI) 10A], a nonblind phase II comparison with alteplase (TIMI 10B), and a randomized double-blind phase III comparison with alteplase in 16 949 patients [the second Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) trial]. Patients also received aspirin and intravenous heparin in all trials. In TIMI 10A and 10B, TIMI grade 3 coronary flow was achieved after 90 minutes in 54.3 to 65.8% of patients receiving tenecteplase 30, 40 or 50 mg; in TIMI 10B, grade 3 flow was reported in 62.7% patients receiving alteplase (</=100mg by front-loaded infusion over 90 minutes). Thirty-day mortality was similar with bodyweight-adjusted intravenous bolus doses of tenecteplase 30 to 50mg and front-loaded 90-minute infusion of alteplase in ASSENT-2 (approximately 6.2%). Rates of reinfarction and cardiogenic shock were also similar between groups, although mortality was reduced with tenecteplase in patients receiving treatment more than 4 hours after onset of symptoms (7 vs 9.2%; p = 0.018). Preliminary data show maintenance of the similarity between groups over 1 year (approximate 10.2% mortality in both groups), with loss of statistical significance between groups in patients treated late. ASSENT-2 showed the risks of intracranial hemorrhage (0.93%) and stroke (all causes) [1.78%] with tenecteplase to be similar to those with alteplase (0.94 and 1.66%, respectively). The rate of noncerebral bleeding was lower with tenecteplase than with alteplase (26.43 vs 28.95%; p = 0.0003). No causal link has been demonstrated between tenecteplase and allergic reactions in patients. Conclusions: Bolus tenecteplase is an effective thrombolytic agent, suitable for first-line use in patients with AMI with ST segment elevation. Results to date show overall efficacy and tolerability profiles similar to those of alteplase, with comparable mortality after 1 year's follow-up. The apparent advantages of tenecteplase (reduced mortality in patients receiving late treatment and reduced incidence of noncerebral bleeding complications) in ASSENT-2 are of interest and merit further attention. The full implications of the availability of bolus administration and its potential clinical advantages over the currently widely used infusion regimens, together with the effect on outcomes of addition of tenecteplase to platelet glycoprotein IIb/IIIa inhibition, are currently under investigation.
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Acute arteriovenous fistulas have been reported after pacemaker lead extraction. We report a case of an arteriovenous fistula presenting 2 weeks after transvenous laser-assisted lead extraction.
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The use of laser technology for the removal of pacemaker and defibrillator leads has decreased the lead extraction time and improved the success rate for complete lead removal when compared to traditional techniques. However, this extraction method may be associated with significant complications. This report documents two cases of iatrogenic arteriovenous fistula created by laser lead extraction. Endovascular repair of these fistulas provides an effective and less invasive alternative to open repair.
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Implantation of a HeartMate II or a Jarvik 2000 FlowMaker left ventricular assist system (LVAS) usually involves a mid-line sternotomy and the use of cardiopulmonary bypass (CPB). In patients with numerous co-morbid conditions, however, surgical trauma may be minimized by implanting the LVAS via a minimally invasive approach, preferably without CPB. In 6 patients with end-stage heart failure and other serious co-morbidities, we implanted a HeartMate II (n = 3) or a Jarvik 2000 FlowMaker (n = 3) LVAS via a right mini-thoracotomy and a left sub-costal incision. Patients included 3 men and 3 women with a mean age of 41 years. In 3 cases, the LVAS was implanted without CPB. After a mean follow-up period of 6 months, 5 patients are alive and well and on the transplant waiting list. Seven months after LVAS implantation, the remaining patient developed a hemorrhagic stroke necessitating Jarvik 2000 replacement with a new pump of the same type. In this small series, the combined sub-costal and mini-thoracotomy incision proved safe and technically feasible. It may be useful for other LVAS candidates who have serious co-morbidities that preclude traditional implant operations.