Antithrombotic therapy for left ventricular assist devices in adults: a systematic review.

BACKGROUND: Left ventricular assist devices (LVADs) have dramatically increased the survival of adults with end-stage systolic heart failure. However, rates of bleeding and thromboembolism remain high. OBJECTIVES: We completed a systematic review to evaluate outcomes of adults with LVADs treated with various anticoagulant and antiplatelet strategies. METHODS: Databases were searched using the terms 'assist device', 'thrombosis', and 'anticoagulant' or 'platelet aggregation inhibitor' with appropriate synonyms, device names and manufacturers. RESULTS AND CONCLUSIONS: Of 977 manuscripts, 24 articles met the inclusion criteria of adults with implanted LVADs where clinical outcomes were defined based on anticoagulant and/or antiplatelet regimen. Most studies reported treatment with unfractionated heparin post-operatively which was transitioned to a vitamin K antagonist (VKA). Goal INR varied between 1.5-3.5. Antiplatelet regimens ranged from no treatment to dual therapy. Definition of major bleeding differed between trials and incidence varied between 0% and 58%. The available evidence could not demonstrate a clear benefit of aspirin compared with VKA therapy alone [stroke RR 1.02 (95% CI 0.49-2.1)]. There was a suggestion that treatment with aspirin and dipyridamole decreased the risk of thromboembolism compared to aspirin [RR 0.50 (0.36-0.68)], but the comparison is limited by differences in demographics, devices, and INR goals among studies. Additionally, most studies did not blind investigators to outcomes thus contributing to an increased risk for bias. Clinical equipoise exists as to the most appropriate antithrombotic therapy in LVAD patients. Randomization between regimens within a prospective trial is needed to define the treatment regimen that minimizes both bleeding and thrombotic complications.

Donor myocardial HIF-1alpha is an independent predictor of cardiac allograft dysfunction: a 7-year prospective, exploratory study.

Knowledge on interplay between the cardiac molecular response to transplantation-induced stress and primary graft dysfunction (PGD) is limited. A cDNA array identified HIF-1, EGR-1, NAB-2, VEGF-A and uPA as mediators of cardiac tissue response to transplantation-induced stress. mRNA expression of these molecules was measured in left ventricular biopsies from 200 donors before and after aortic cross-clamping and at 10-, 30- and 60-min reperfusion by real-time RT-PCR. HIF-1alpha expression at two time points was significantly associated with PGD, as shown by univariate analysis, receiver operating characteristic curve and multivariate logistic regression. At a cut-off level of 200 arbitrary units, HIF-1alpha after aortic cross-clamping in donors (78% sensitivity, 83% specificity) and at 10-min reperfusion (85% sensitivity, 83% specificity) identified PGD. HIF-1alpha demonstrates the potential to be a predictive marker for PGD; however, as multiple factors were tested at different time points, prospective evaluation is clearly necessary to confirm this observation.

Posttraumatic stress disorder after implantation of a mechanical assist device followed by heart transplantation: evaluation of patients and partners.

AIM: We sought to investigate the prevalence of posttraumatic stress disorder, anxiety, and depression in patients and their partners after implantation of a mechanical assist device as a bridge to heart transplantation. METHODS: This was a retrospective assessment of 41 patients (age 46.3 +/- 12.0 years; male-female ratio, 38:3; time since transplantation, 55.3 +/- 34.2 months [range, 7-122 months) and 27 partners (male-female ratio 2:25) by standardized instruments (Impact of Event Scale, Hospital Anxiety and Depression Scale), in 2 University Heart Transplant Centers (Vienna, Austria, Munster, Germany). The duration of the support systems (MicroMed DeBakey-VAD in 17 patients, Novacor in 10, Thoratec in 8, TCI HeartMate in 5, and Berlin Heart Incor in 1 patient) ranged from 28 to 711 (176 +/- 146) days. RESULTS: None of the patients, but 23% of the partners (n = 6), met the criteria for posttraumatic stress disorder (Maercker cutoff >0). The Impact of Event Scale (IES) sum scales differed significantly between the 2 groups (21.2 +/- 15.1, mean +/- SD) for the patients versus 38.1 +/- 27.8 for the partners, respectively; P = .001). Two percent of the patients, but 19% of the partners, showed mild to moderate depression; 4% of patients, but 23% of their partners, reported mild to moderate anxiety. None of the results were significantly influenced by the time since transplantation, patient age, diagnoses, type of assist device, or indication for heart transplantation. CONCLUSIONS: Despite patients being much closer to a life threat, their partners experience significantly more psychologic distress even in the long run. Our findings highlight the need for attention to the supporting persons.

Rapamycin as rescue therapy in a patient supported by biventricular assist device to heart transplantation with consecutive ongoing rejection.

Rapamycin is a new immunosuppressive agent that has been shown to be effective in acute heart allograft rejection. This case documents a patient suffering from cardiac sarcoidosis who was bridged to transplantation for 90 days with ongoing rejection after allograft implantation. Rejection did not abate despite treatment with antithymocyte globulin (ATG), FK506, a mycophenolate switch and courses of multiple apheresis. Initiation of rapamycin treatment resulted in a rapid resolution of cardiac rejection and reduction of concomitant immunosuppressive agents with few side-effects. Most notably was the reduction of panel reactive antibodies within a few weeks after the rapamycin initiation. This case illustrates that the utilization of rapamycin ceased ongoing rejection in a patient with a clear hyperimmune state despite prior extensive utilization of a variety of immunosuppressive strategies after heart transplantation.

Transitory immunologic response after implantation of the DeBakey VAD continuous-axial-flow pump.

BACKGROUND: The development of local and systemic infection is a significant risk factor associated with implantation of a ventricular assist device. The immunologic consequence of continuous-flow rotary blood pumps is not known. METHODS: Six male adult patients (mean age 47 plus minus 10.3) with end-stage left heart failure received a DeBakey VAD axial-flow pump for use as a bridge to transplantation. (Four patients underwent transplantation after a mean 115 plus minus 14 days; 2 patients are still waiting for the allograft.) RESULTS: We prospectively monitored T-cell populations and apoptosis-specific aberrant T-cell activation via CD95 triggering and annexin V binding to lymphocytes, identifying T cells undergoing early phases of apoptosis, within the first 10 weeks. Moreover, soluble death-inducing receptors soluble CD95 and soluble tumor necrosis factor-R1 were evaluated by enzyme-linked immunosorbent assay. CONCLUSION: Patients bridged to transplantation by a nonpulsatile ventricular assist device demonstrated an initial pronounced apoptosis-specific immune alteration by increased annexin V binding to CD3 T cells and death-inducing receptors soluble CD95/tumor necrosis factor-R1 (all P <.001). All parameters normalized after 7 weeks to baseline. No blood-borne sepsis was detected, as defined by blood culture, within the first 10 weeks of the cohort study. These results indicate a biphasic immunologic response in patients with end-stage heart failure treated with nonpulsatile ventricular assist devices.

Survival benefit of the implantable cardioverter-defibrillator in patients on the waiting list for cardiac transplantation.

BACKGROUND: The implantable cardioverter-defibrillator (ICD) effectively reduces sudden cardiac death in patients with severe LV dysfunction. Effect of ICD therapy on total mortality in patients on the waiting list for cardiac transplantation is still uncertain. METHODS AND RESULTS: We retrospectively analyzed 854 unselected consecutive patients (ICD therapy, n=102; 11.9%) on the waiting list for cardiac transplantation between January 1992 and March 2000. Actuarial 12-month total mortality rate on the waiting list was 24.2%; sudden cardiac death was the predominant mode of death (66.7% of total deaths). Kaplan-Meier analysis revealed improved survival for ICD (total mortality, 13.2%) compared with non-ICD (total mortality, 25.8%) patients (log rank, P=0.03). No event of sudden death occurred in ICD patients, whereas in non-ICD patients, 12-month sudden death rate was 20.1% (P=0.0001). Nonsudden death rates did not differ between ICD and non-ICD patients (P=0.16). A Cox proportional hazards model demonstrated that absence of an ICD was a powerful independent predictor of total mortality (P=0.02; relative risk, 2.22; 95% confidence interval, 1.16 to 4.17) and sudden cardiac death (P<0.0001; infinite relative risk) on the waiting list. CONCLUSIONS: ICD therapy, because it prevents sudden cardiac death, significantly improves survival on the waiting list for cardiac transplantation. The present study supports the use of ICDs as a bridge to transplantation in patients who are at risk of sudden cardiac death. Prospective randomized trials are needed to evaluate the potential benefit of prophylactic ICD therapy as a bridge to transplantation in all patients on cardiac transplant waiting lists.

Late aortic dissection in a patient with a left ventricular assist device.

The limited availability of donor hearts means that an increasing number of transplantation candidates are temporarily or permanently supported by mechanical circulatory assist devices. We report a patient undergoing implantation of a Novacor left ventricular assist device who suffered fatal aortic dissection on postoperative day 11 after satisfactory recovery from multiple organ failure. The dissection of the aorta initially presented as an embolic peripheral ischemia. Early complete echocardiography is thus warranted to rule out dissection.

First experiences with outpatient care of patients with implanted axial flow pumps.

As known from patients with pulsatile ventricular assist devices (VADs), early mobilization, physical exercise, and return to normal life are essential for optimal recovery. Recently, implantable rotary pumps became available for extended left ventricular support as bridges to transplantation. Modified procedures are essential for patient training and hospital discharge. The MicroMed-DeBakey VAD was implanted in 10 patients with end-stage heart disease. After recovery, regular ergometer training was performed with loads adapted to the patient's condition. Procedures for patient observation under outdoor conditions and a blood pressure measuring device for low pulse pressure conditions were developed. Improvement of physical condition was achieved in 8 patients. In the first 2 patients, exercise capacity was limited due to flow obstruction. In the following patients, an increase of workload on the ergometer up to 120 W was observed. Correlated with training, lactate/load relationship and heart rate decreased. Three patients were discharged from the hospital during support. The DeBakey-VAD system can support patients for extended time periods and is suitable for recovery and exercise. Under optimal patient and environmental conditions, discharge from the hospital can be obtained.

Lessons learned from the first clinical implants of the DeBakey ventricular assist device axial pump: a single center report.

BACKGROUND: The bridge to transplantation with pulsatile mechanical assist devices became a standard procedure for patients deteriorating on the waiting list. Recently, continuous flow axial impeller pumps were introduced to clinical application offering new advantages. METHODS: From November 1998 till September 2000, 6 male patients (mean age 53 plus or minus 11 years) with end-stage left heart failure were implanted with a DeBakey ventricular assist device (VAD) axial-flow pump for bridge to transplantation. RESULTS: Three patients were successfully transplanted after 74, 115, and 117 days, respectively. Two other patients died after 25 and 133 days. One patient is still on the device after 108 days. Because of modification of the implantation technique after the first 2 patients, mean pump-flow within the first 3 weeks was increased from 4.3 +/- 0.6 L/min to 6.7 +/- 0.3 L/min. Patients were put on regular bicycle-ergometer training and improved their exercise capacities up to a mean maximum oxygen consumption of 20.2 mL/kg/min. CONCLUSIONS: Initial implants of the DeBakey VAD demonstrated support properties comparable to pulsatile pumps but without significant restrictions for extended use.

Mechanical circulatory support for advanced heart failure: effect of patient selection on outcome.

BACKGROUND: Use of wearable left ventricular assist systems (LVAS) in the treatment of advanced heart failure has steadily increased since 1993, when these devices became generally available in Europe. The aim of this study was to identify in an unselected cohort of LVAS recipients those aspects of patient selection that have an impact on postimplant survival. METHODS AND RESULTS: Data were obtained from the Novacor European Registry. Between 1993 and 1999, 464 patients were implanted with the Novacor LVAS. The majority had idiopathic (60%) or ischemic (27%) cardiomyopathy; the median age at implant was 49 (16 to 75) years. The median support time was 100 days (4.1 years maximum). Forty-nine percent of the recipients were discharged from the hospital on LVAS; they spent 75% of their time out of the hospital. For a subset of 366 recipients, for whom a complete set of data was available, multivariate analysis revealed that the following preimplant conditions were independent risk factors for survival after LVAS implantation: respiratory failure associated with septicemia (odds ratio 11.2), right heart failure (odds ratio 3.2), age >65 years (odds ratio 3.01), acute postcardiotomy (odds ratio 1.8), and acute infarction (odds ratio 1.7). For patients without any of these factors, the 1-year survival after LVAS implantation including the posttransplantation period was 60%; for the combined group with at least 1 risk factor, it was 24%. CONCLUSIONS: Careful selection, specifically implantation before patients become moribund, and improvement of management may result in improved outcomes of LVAS treatment for advanced heart failure.

First clinical experience with the DeBakey VAD continuous-axial-flow pump for bridge to transplantation.

BACKGROUND: A shortage of donor organs and increased numbers of deaths of patients on the waiting list for cardiac transplantation make mechanical circulatory support for a bridge to transplantation a standard clinical procedure. Continuous-flow rotary blood pumps offer exciting new perspectives. METHODS AND RESULTS: Two male patients (ages 44 and 65 years) suffering from end-stage left heart failure were implanted with a DeBakey VAD axial-flow pump for use as a bridge to transplant. In the initial postoperative period, the mean pump flow was 3.9+/-0.5 L/min, which equals a mean cardiac index (CI) of 2.3+/-0.2 L. min(-1). m(-2). In both patients, the early postoperative phase was characterized by a completely nonpulsatile flow profile. However, with the recovery of heart function 8 to 12 days after implantation, increasing pulse pressures became evident, and net flow rose to 4.5+/-0.6 L/min, causing an increase of mean CI up to 2.7+/-0.2 L. min(-1). m(-2). Patients were mobilized and put through regular physical training. Hemolysis stayed in the physiological range and increased only slightly from 2. 1+/-0.8 mg/dL before surgery to 3.3+/-1.8 mg/dL 6 weeks after implantation. CONCLUSIONS: The first clinical implants of the DeBakey VAD axial-flow pump have demonstrated the device to be a promising measure of bridge-to-transplant mechanical support.

[The DeBakey VAD axial flow pump: first clinical experience with a new generation of implantable, nonpulsatile blood pumps for long-term support prior to transplantation]. / Die DeBakey VAD-Axialpumpe: Erste klinische Erfahrungen mit einer neuen Generation von implantierbaren, nonpulsatilen Blutpumpen als Langzeit-Uberbrückung bis zur Transplantation.

Because of the high frequency of acute hemodynamic deterioration in patients awaiting cardiac transplantation, mechanical techniques of circulatory support to bridge the period until transplantation have become a standard clinical procedure. Continuous-flow rotary blood pumps offer exciting new perspectives in terms of ventricular assistance and/or as a total cardiac substitute. A DeBakey VAD axial flow pump was implanted in two male patients (aged 44 and 65 years, respectively) suffering from end-stage left heart failure. In the initial postoperative period the mean flow rate of the pump was 3.9 +/- 0.5 l/min. In both patients, the early postoperative phase was characterised by a completely non-pulsatile flow profile. Two weeks after implantation and partial recovery of the natural left ventricle, increasing pulse pressures became evident and net flow increased to 4.5 +/- 0.6 l/min. Patients were mobilised and made to under-go regular physical training. Hemolysis produced by the pump was low while free haemoglobin stayed in physiological ranges, increasing only slightly from 2.1 +/- 0.8 mg/dl preoperatively to 3.0 +/- 1.5 mg/dl ten weeks after implantation. One patient was successfully transplanted on day 74 after implantation of the DeBakey VAD while the second patient is, after 110 days of pumping, still waiting for transplantation. This first experience concerning clinical implantation of the DeBakey VAD axial flow pump showed that the device is promising as a means of providing mechanical support to bridge the period until cardiac transplantation.