The HeartWare left ventricular assist device (HVAD, HeartWare Inc, Framingham, MA) 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 pre-disposing to the development of pump thrombus.
The analysis included 382 patients who underwent implantation of the HVAD as part of the HeartWare Bridge to Transplant (BTT) and subsequent Continued Access Protocol (CAP) trial. 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.
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 (50%). A total of 16 patients underwent pump exchange, and 2 underwent urgent transplantation. Five patients with a pump thrombus died after medical therapy failed, 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%, respectively (p = 0.21). A multivariable analysis revealed that significant risk factors for pump thrombus included a mean arterial pressure > 90 mm Hg, aspirin dose ≤ 81 mg, international normalized ratio ≤ 2, and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile level of ≥ 3 at implant.
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 sub-optimal anti-coagulation and anti-platelet therapies. This suggests that pump thrombus event rates could be reduced through careful adherence to patient management guidelines.
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.
The recent success of continuous-flow circulatory support devices has led to the growing acceptance of these devices as a viable therapeutic option for end-stage heart failure patients who are not ...responsive to current pharmacologic and electrophysiologic therapies. This article defines and clarifies the major classification of these pumps as axial or centrifugal continuous-flow devices by discussing the difference in their inherent mechanics and describing how these features translate clinically to pump selection and patient management issues. Axial vs centrifugal pump and bearing design, theory of operation, hydrodynamic performance, and current vs flow relationships are discussed. A review of axial vs centrifugal physiology, pre-load and after-load sensitivity, flow pulsatility, and issues related to automatic physiologic control and suction prevention algorithms is offered. Reliability and biocompatibility of the two types of pumps are reviewed from the perspectives of mechanical wear, implant life, hemolysis, and pump deposition. Finally, a glimpse into the future of continuous-flow technologies is presented.
Stroke is a major cause of mortality after left ventricular assist device (LVAD) placement.
Prospectively collected data of patients with HeartMate II (n = 332) and HeartWare (n = 70) LVADs from ...October 21, 2004, to May 19, 2015, were reviewed. Predictors of early (during index hospitalization) and late (post-discharge) ischemic and hemorrhagic stroke and association of stroke subtypes with mortality were assessed.
Of 402 patients, 83 strokes occurred in 69 patients (17%; 0.14 events per patient-year EPPY): early ischemic stroke in 18/402 (4%; 0.03 EPPY), early hemorrhagic stroke in 11/402 (3%; 0.02 EPPY), late ischemic stroke in 25/402 (6%; 0.04 EPPY) and late hemorrhagic stroke in 29/402 (7%; 0.05 EPPY). Risk of stroke and death among patients with stroke was bimodal with highest risks immediately post-implant and increasing again 9-12 months later. Risk of death declined over time in patients without stroke. Modifiable stroke risk factors varied according to timing and stroke type, including tobacco use, bacteremia, pump thrombosis, pump infection, and hypertension (all p < 0.05). In multivariable analysis, early hemorrhagic stroke (adjusted odds ratio aOR 4.3, 95% confidence interval CI 1.0-17.8, p = 0.04), late ischemic stroke (aOR 3.2, 95% CI 1.1-9.0, p = 0.03), and late hemorrhagic stroke (aOR 3.7, 95% CI 1.5-9.2, p = 0.005) predicted death, whereas early ischemic stroke did not.
Stroke is a leading cause and predictor of death in patients with LVADs. Risk of stroke and death among patients with stroke is bimodal, with highest risk at time of implant and increasing risk again after 9-12 months. Management of modifiable risk factors may reduce stroke and mortality rates.
Objective The aim of this study was to evaluate the incidence, risk factors, and effect on outcomes of right ventricular failure in a large population of patients implanted with continuous-flow left ...ventricular assist devices. Methods Patients (n = 484) enrolled in the HeartMate II left ventricular assist device (Thoratec, Pleasanton, Calif) bridge-to-transplantation clinical trial were examined for the occurrence of right ventricular failure. Right ventricular failure was defined as requiring a right ventricular assist device, 14 or more days of inotropic support after implantation, and/or inotropic support starting more than 14 days after implantation. Demographics, along with clinical, laboratory, and hemodynamic data, were compared between patients with and without right ventricular failure, and risk factors were identified. Results Overall, 30 (6%) patients receiving left ventricular assist devices required a right ventricular assist device, 35 (7%) required extended inotropes, and 33 (7%) required late inotropes. A significantly greater percentage of patients without right ventricular failure survived to transplantation, recovery, or ongoing device support at 180 days compared with patients with right ventricular failure (89% vs 71%, P < .001). Multivariate analysis revealed that a central venous pressure/pulmonary capillary wedge pressure ratio of greater than 0.63 (odds ratio, 2.3; 95% confidence interval, 1.2–4.3; P = .009), need for preoperative ventilator support (odds ratio, 5.5; 95% confidence interval, 2.3–13.2; P < .001), and blood urea nitrogen level of greater than 39 mg/dL (odds ratio, 2.1; 95% confidence interval, 1.1–4.1; P = .02) were independent predictors of right ventricular failure after left ventricular assist device implantation. Conclusions The incidence of right ventricular failure in patients with a HeartMate II ventricular assist device is comparable or less than that of patients with pulsatile-flow devices. Its occurrence is associated with worse outcomes than seen in patients without right ventricular failure. Patients at risk for right ventricular failure might benefit from preoperative optimization of right heart function or planned biventricular support.
Objectives This study sought to evaluate the use of a continuous-flow rotary left ventricular assist device (LVAD) as a bridge to heart transplantation. Background LVAD therapy is an established ...treatment modality for patients with advanced heart failure. Pulsatile LVADs have limitations in design precluding their use for extended support. Continuous-flow rotary LVADs represent an innovative design with potential for small size and greater reliability by simplification of the pumping mechanism. Methods In a prospective, multicenter study, 281 patients urgently listed (United Network of Organ Sharing status 1A or 1B) for heart transplantation underwent implantation of a continuous-flow LVAD. Survival and transplantation rates were assessed at 18 months. Patients were assessed for adverse events throughout the study and for quality of life, functional status, and organ function for 6 months. Results Of 281 patients, 222 (79%) underwent transplantation, LVAD removal for cardiac recovery, or had ongoing LVAD support at 18-month follow-up. Actuarial survival on support was 72% (95% confidence interval: 65% to 79%) at 18 months. At 6 months, there were significant improvements in functional status and 6-min walk test (from 0% to 83% of patients in New York Heart Association functional class I or II and from 13% to 89% of patients completing a 6-min walk test) and in quality of life (mean values improved 41% with Minnesota Living With Heart Failure and 75% with Kansas City Cardiomyopathy questionnaires). Major adverse events included bleeding, stroke, right heart failure, and percutaneous lead infection. Pump thrombosis occurred in 4 patients. Conclusions A continuous-flow LVAD provides effective hemodynamic support for at least 18 months in patients awaiting transplantation, with improved functional status and quality of life. (Thoratec HeartMate II Left Ventricular Assist System LVAS for Bridge to Cardiac Transplantation; NCT00121472 )
Drive-line infections (DLIs) frequently complicate ventricular assist device (VAD) support. We sought to describe the detailed effects of DLIs over time in patients with continuous-flow VADs, ...including the onset, risk factors, organisms involved, association with invasive infections, and outcomes.
We reviewed data for patients with HeartMate II VADs (HMII) who were implanted at the Cleveland Clinic from October 2004 to September 2011 and followed through December 2011. DLIs were defined according to published criteria.
DLIs developed in 45 of 194 HMII VADs over a median period of 232 days (range 22 to 883 days). Hazard for DLI was 2.0%/month, but transiently peaked at 11%/month at 7.5 months after implant. Pseudomonas aeruginosa accounted for 31%, 42% and 55% of initial, final and deep DLIs, respectively. Of the 40 superficial DLIs, 13 (32.5%) became deep. DLI-associated bacteremia and hospitalization occurred in 14 of 45 (31%) and 30 of 45 (67%), respectively. All patients received antibiotics (median 171 days), but only 3 of 44 (6.8%) developed an antibiotic complication. DLIs increased the risk for death while on VAD support (HR 2.20, 95% CI 1.20 to 4.05; p = 0.01). Six and 12 months after DLI, mortality was 9.8% and 31%, but the competing event of transplantation occurred successfully in 20% and 28%, respectively.
Most DLIs begin superficially with peak hazard at 7.5 months after implant. Depth of infection and infecting organism may evolve over months on support, with Pseudomonas becoming more prominent. Although effectively managed for prolonged periods, DLIs are associated with reduced survival on VAD support. Earlier transplantation is the most successful approach to treatment.
Continuous-flow left ventricular assist devices (LVAD) are increasingly being used in patients with end-stage heart failure and have largely replaced older generation pulsatile devices. While ...significant rates of infection have been reported in patients with pulsatile device support, incidence and outcomes of this complication for the continuous-flow device patients remain unknown.
Between June 2005 and August 2009, 81 patients were implanted with continuous-flow LVADs at Washington University School of Medicine either as bridge to transplantation or as destination therapy. Outcomes of this study included incidence of postimplantation infection, types of infection, microbiologic profile, and association of postimplantation infections with clinical endpoints.
Forty-two patients (51.9%) had at least one type of infection on continuous-flow LVAD support with a mean follow-up period of 9.2 ± 9.2 months. Patients who had an infection on LVAD support had a significantly prolonged hospital stay (37.9 ± 32.0 versus 20.7 ± 23.0 days, p = 0.008) and a trend toward increased mortality (33.1% versus 18.7% at 2 years, respectively, log rank p = 0.102) compared with patients who did not. Subgroup analysis revealed that postimplantation sepsis was significantly associated with increased mortality in the continuous-flow LVAD cohort (61.9% versus 18.0% at 2 years, respectively, in septic and nonseptic patients, log rank p = 0.001). The majority of the sepsis cases occurred before hospital discharge, whereas most of the device related infections occurred after discharge. Resistant Staphylococcus and Pseudomonas species were the most common pathogens leading to device- and nondevice-related local infections. Development of driveline or pocket infection had no effect on survival in patients with continuous-flow assist device support (p = 0.193).
Even though better clinical outcomes have been achieved with the newer generation continuous-flow devices, infection complications-in particular sepsis-are still a major risk for patients with continuous-flow LVAD implantation. Prevention strategies with aggressive medical and surgical management of infections may increase survival and decrease morbidity among continuous-flow LVAD patients.
Although continuous-flow left ventricular assist devices (LVAD) are durable and reliable, device replacement will be inevitable in some patients. We evaluated the incidence and outcomes of pump ...replacement procedures with the HeartMate II (Thoratec Corporation, Pleasanton, CA) LVAD.
Data were obtained from 1,128 patients implanted from March 2005 to January 2010 with the HeartMate II during the clinical trials for bridge to transplant and destination therapy. The operative mortality associated with the replacement procedure was determined.
The mean duration of HeartMate II support was 568 ± 535 days (cumulative duration: 1,755 patient-years, longest: 6.5 years). A total of 72 (6.4%) patients underwent 79 LVAD replacements (0.045 events/patient-year) of which 2 were in the initial operation and 77 in separate procedures. Reasons for replacement were percutaneous lead damage (36 events, 3.0%), device thrombosis (25 events, 2.1%), infection (7 events, 0.6%), and miscellaneous other (11 events, 0.9%). The median time to pump replacement was 428 days (range 0 to 1,474). Of the 77 replacement procedures, there were 5 (6.5%) operative deaths within 30 days. The causes of death were device thrombosis, right heart failure, multisystem organ failure, and bleeding. One year after exchange (median 2.1 years after initial implant), 30% had died, 5% were transplanted, and 65% were ongoing and alive.
HeartMate II device failure requiring pump replacement is infrequent, but when required can be done safely. These data continue to provide encouraging evidence supporting HeartMate II use for long-term circulatory support.
The HeartMate II (Thoratec, Pleasanton, CA) is an effective bridge to transplantation (BTT) but requires anti-coagulation with warfarin and aspirin. We evaluated the risk of thromboembolism and ...hemorrhage related to the degree of anti-coagulation as reflected by the international normalized ratio (INR).
INRs were measured monthly for 6 months in all discharged HeartMate II BTT patients and at an event. Each INR was assigned to ranges of INRs. Adverse events analyzed were ischemic and hemorrhagic stroke, pump thrombosis, and bleeding requiring surgery or transfusion. Events were correlated to the INR during the event and at the start of the month.
In 331 patients discharged on support, 10 had thrombotic events (9 ischemic strokes, 3 pump thromboses), and 58 had hemorrhagic events (7 strokes, 4 hemorrhages requiring surgery, and 102 requiring transfusions). The median INR was 2.1 at discharge and 1.90 at 6 months. Although the incidence of stroke was low, 40% of ischemic strokes occurred in patients with INRs < 1.5 and 33% of hemorrhagic strokes were in patients with INRs > 3.0. The highest incidence of bleeding was at INRs > 2.5.
The rate of thromboembolism during long-term outpatient support with the HeartMate II is low. The low number of thrombotic events appears to be offset by a greater number of hemorrhagic events. An appropriate target INR is 1.5 to 2.5 in addition to aspirin therapy. In patients having recurrent episodes of bleeding, the risk of lowering the target INR appears to be small.
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