Circulatory support exceeding five years with a continuous-flow left ventricular assist device for advanced heart failure patients.

Continuous-flow left ventricular assist devices (CF-LVAD) are now providing years of safe circulatory support with enhanced quality of life. We present four cases of patients with advanced heart failure who received support for greater than 5-years with the HeartMate II CF-LVAD. One patient continues with support at 7.5 years and has decided to not undergo cardiac transplantation. Another patient has also had LVAD support for 7.7 years, initially with a pulsatile flow LVAD, and then was switched to the HeartMate II, which has continued to support him for the last 6.6 years. Two other patients have undergone heart transplant after support times of 5.46 years and 5.75 years. Few complications occurred and the patients had very active lifestyles during support. Explant analysis revealed very low bearing wear and minimal pannus.

Acquired von Willebrand syndrome in patients with a centrifugal or axial continuous flow left ventricular assist device.

OBJECTIVES: The aim of this study was to determine whether differences in continuous flow left ventricular assist devices (LVADs) may lead to differences in the von Willebrand profile and the occurrence of bleeding and thromboembolic events. BACKGROUND: The HeartMate II (Thoratec Corp., Pleasanton, California) and HeartWare Ventricular Assist Device (HVAD) (HeartWare, Inc., Framingham, Massachusetts) systems are the most frequently implanted LVADs worldwide. In all patients with an axial-flow HeartMate II, acquired von Willebrand syndrome (AvWS) due to the loss of large molecular weight multimers was found. The large molecular weight multimers of the von Willebrand factor (vWF) play a key role in primary hemostasis through interactions with platelets. METHODS: This was a retrospective study of the vWF profile and incidence of bleeding and thromboembolic events in 102 patients receiving the HeartMate II (n = 51) and HVAD (n = 51). Between January 2003 and December 2010, vWF testing was performed in 102 of 175 consecutive patients after LVAD implantation. RESULTS: AvWS was found in all patients, demonstrated by a decrease in the high molecular weight multimers of vWF to 30 ± 14% in HeartMate II patients and 34 ± 13% in patients with an HVAD. Significant predictors of vWF antigen included age (p = 0.011), number of days on the device (p = 0.035), C-reactive protein (p < 0.001), and blood group (p = 0.007). Bleeding and thromboembolic event rates were similar. However, lower fractions of vWF antigen and high molecular weight multimers did not correlate with the rate of bleeding complications or thromboembolic events. CONCLUSIONS: AvWS developed in all patients after centrifugal or axial flow pump implantation. Different patterns of AvWS were seen between the devices as well as individually. However, the complication rates after implantation were similar.

Steroid withdrawal and reduction of cyclosporine A under mycophenolate mofetil after heart transplantation.

Survival and quality of life after heart transplantation are limited by a significant incidence of cardiovascular complications. Side effects of immunosuppressives contribute unfavorably. Aim of this study was to determine (1) whether withdrawal of corticosteroids and dose reduction of cyclosporine A can be performed safely under immunosuppressive therapy with mycophenolate mofetil and (2) if this is beneficial for renal function and cardiovascular risk reduction. Long term heart transplant recipients on steroids and cyclosporine A were examined in a monocentric, prospective, single-arm cohort study. Steroids were withdrawn, mycophenolate mofetil introduced and cyclosporine A dose reduced (target level 50-90 ng/ml). Follow up was 24 months. 23 patients were analyzed: Renal parameters (creatinine, urea, uric acid) improved significantly (p<0.01), as did cardiovascular parameters (heart rate [p<0.05], systolic and diastolic blood pressure [p<0.01]), HbA1c (p<0.05) and triglycerides (p<0.05). In contrast, the self-percepted state of health (SF36™) decreased. Drop outs occurred mostly due to steroid withdrawal syndrome [n=7]. The incidence of adverse events reflected the usual course after heart transplantation. We conclude that CS free immunosuppression comprising reduced cyclosporine levels and addition of MMF in long term heart transplant recipients is safe and improves the cardiovascular risk profile, carbohydrate metabolism and renal function.

Reduction of driveline infections through doubled driveline tunneling of left ventricular assist devices.

The durability of ventricular assist device (VAD) therapy improved steadily over the past years. However, driveline infections remain a challenge. To test whether an improved surgical implantation technique may lower the incidence of infections, we analyzed all patients receiving a VAD implantation in the years 2008 and 2009 (group 1) and compared them with all patients who received a VAD in 2011 (group 2) after we changed our implantation method. The new technique involves tunneling of the driveline into the fascia of the musculus rectus abdominis, resulting in a longer, intrafascial run to achieve a better resistance against ascending infections. We retrospectively analyzed 40 patients in group 1 and 41 patients in group 2. One year after implantation, the infection rate was markedly reduced (22.5% [n = 9] group 1 vs. 4.9% [n = 2] group 2, P < 0.001) by the new implantation method. There was, however, no significant improvement in overall mortality. The Cox regression model identified the implantation method as an independent risk factor for 1 year after implantation driveline infection (P < 0.05). In conclusion, the new tunneling technique marks a great leap forward in long-term VAD treatment. However, overall mortality remains high and needs further improvement.

Symptom experiences in patients after heart transplantation.

Patients' perceptions of immunosuppression-related symptom experience impact on quality of life and medication adherence. Using The Modified Transplant Symptom Occurrence and Symptom Distress Scale capturing items on symptom occurrence and symptom distress, 261 heart transplant recipients reported on their symptom experiences. Symptoms occurring with the highest prevalence were tiredness, lack of energy, and nervousness. Men showed erectile dysfunction causing the most distress. Women and younger patients reported significantly higher levels of symptom distress. Distress levels increased with time after transplant. Investigating responses to immunosuppression-related symptom experiences should help develop interventional methods to support long-term outcome.

Implantation of rotary blood pumps into 115 patients: a single-centre experience.

OBJECTIVES: From 2004 to 2009, rotary blood pumps were implanted for heart failure as a bridge to transplant or destination therapy in 101 male and 14 female patients at our institution. We report on our experiences of these patients with a follow-up of 132 patient years. METHODS: Seventy-four HeartMate II axial flow pumps and 41 HeartWare centrifugal pumps were implanted in patients with non-ischaemic (n = 70) or ischaemic cardiomyopathy (n = 45). The mean age of the patients was 50 ± 13 years. All patients were on inotropic support prior to implantation. Extracorporeal membrane oxygenation was used as a bridging procedure in 21 cases. RESULTS: The perioperative mortality was 14%. Hospital discharge occurred on average after 46 ± 33 days. Twenty-two patients of this cohort received a heart transplant 492 ± 342 days after implantation of the device. Two patients died after heart transplantation. A 1-year survival of 73% and a 2-year survival of 69% were recorded, despite a low incidence of transplant procedures. The longest support time was 1686 days. CONCLUSIONS: Modern left ventricular assist device technology can be used successfully for heart failure. The scarcity of donor hearts leads to prolonged periods on the device, and chronic ventricular assist device therapy has become a reality, although bridge to transplant was intended; therefore, sufficient support services for outpatient care of these patients are required.

Patients with continuous-flow left ventricular assist devices provide insight in human baroreflex physiology.

The superior clinical outcome of new continuous-flow left ventricular assist devices (LVADs) challenges the physiological dogma that cardiovascular autonomic homeostasis requires pulsatile blood flow and pressure. We tested the hypothesis that continuous-flow LVADs impair baroreflex control of sympathetic nerve traffic, thus further exacerbating sympathetic excitation. We included 9 male heart failure patients (26-61 years; 18.9-28.3 kg/m(2)) implanted with a continuous-flow LVAD. We recorded ECG, respiration, finger blood pressure, brachial blood pressure, and muscle sympathetic nerve activity. After baseline measurements had been taken, patients underwent autonomic function testing including deep breathing, a Valsalva maneuver, and 15° head-up tilt. Finally, we increased the LVAD speed in 7 patients. Spontaneous sympathetic baroreflex sensitivity was analyzed. Brachial blood pressure was 99±4 mm Hg with 14±2 mm Hg finger pulse pressure. Muscle sympathetic nerve activity bursts showed a normal morphology, were linked to the cardiac cycle, and were suppressed during blood pressure increases. Mean burst frequency was lower compared with age- and body mass index-matched controls in 2 patients, slightly increased in 4 patients, and increased in 2 patients (P=0.11). Muscle sympathetic nerve activity burst latency and the median values of the burst amplitude distribution were similar between groups. Muscle sympathetic nerve activity increased 4±1 bursts per minute with head-up tilt (P<0.0003) and decreased 3±4 bursts per minute (P<0.031) when LVAD speed was raised. The mean sympathetic baroreflex slope was -3.75±0.79%/mm Hg in patients and -3.80±0.55%/mm Hg in controls. We conclude that low pulse pressure levels are sufficient to restrain sympathetic nervous system activity through baroreflex mechanisms.

A multi-modal intervention in management of left ventricular assist device outpatients: dietary counselling, controlled exercise and psychosocial support.

OBJECTIVE: Newer generation left ventricular assist devices (LVADs) are established for long-term support. The aim of this multi-modal intervention was to improve the body weight, exercise tolerance and psychosocial status in outpatients on long-term LVAD support. METHODS: Seventy patients participated in this non-randomized intervention study [intervention group (IGr) n = 34; control group (CGr) n = 36] over 18 months (T1-T4); the baseline sample characteristics showed no differences between groups. Dietary counselling and weight management intervention was performed by a dietician based on a specific algorithm. Physical reconditioning followed a home ergometry protocol and was supplemented by psychosocial counselling. The outcomes were measured based on the body mass index (BMI), cardiopulmonary exercise testing and self-report [hospital anxiety and depression scale (HADS), SF-36]. RESULTS: The intervention showed a strong positive effect on nutrition and weight management [95% confidence interval (CI): -0.71-0.69; effect size (ES): 0.907; P = 0.02)], resulting in the normal BMI (kg/m(2)) values in the IGr (T1: 24.0 ± 0.6; T4: 24.5 ± 1.1; P = 0.35) compared with a significant BMI increase in the CGr (T1: 23.8 ± 0.6; T4: 29.7 ± 0.8; P = 0.05). Significant differences appeared regarding exercise tolerance (VO(2)max/% predicted) in favour of IGr patients (IGr: 69 ± 2.9; CGr 62 ± 3.7; P = 0.04). This increase was reflected by patients' self-reporting based on the SF-36 physical component score (IGr: P = 0.04; CGr: P = 0.54). SF-36 psychosocial component scores showed no changes for both groups. However, CGr showed a tendency for increased anxiety scores relative to their counterparts (IGr: 4.95 ± 0.4; CGr: 6.6 ± 0.9; P = 0.03). CONCLUSIONS: IGr patients showed a strong benefit from a multi-modal intervention, including dietary counselling, controlled exercise and psychosocial support. Dietary counselling holds potential to prevent obesity in this patient population.

Health-related quality of life and exercise tolerance in recipients of heart transplants and left ventricular assist devices: a prospective, comparative study.

BACKGROUND: The aim of this study was to evaluate and compare health-related quality of life (HRQoL) and physical exercise tolerance in patients after heart transplantation (HTx) or implantation of a left ventricular assist device (LVAD). METHODS: A prospective, comparative design was used to characterize changes over time in HRQoL (SF-36) and exercise tolerance in patients after HTx (n = 54) and during LVAD support (n = 36). Nine LVAD patients were lost for follow-up. The majority of patients in both groups were male (97%); the LVAD cohort tended to be younger (p = 0.06). RESULTS: HRQoL improved significantly in HTx patients in the SF-36 physical (p = 0.02), but not in the psychosocial (p = 0.27) component score during follow-up. In the LVAD group, HRQoL showed improvements for both the SF-36 physical and psychosocial component scores (both p = 0.04). Between-group comparisons revealed better HRQoL for the HTx cohort than the LVAD cohort for 2 of 8 SF-36 subscales. Age-, gender- and body mass index (BMI)-adjusted exercise tolerance (workload; VO(2max)) showed significant improvements for both HTx (p = 0.01) and LVAD (p = 0.01) patients. Adjusted maximum oxygen consumption was higher for HTx patients (p = 0.05) relative to LVAD patients at 8 ± 1 months after implant. CONCLUSION: HRQoL and exercise capacity increased in both groups over the time-course of the study. After adjusting for relevant variables, HTx patients showed a higher exercise tolerance compared with the LVAD group during follow-up. Thus, future large-scale intervention studies should emphasize the specific needs of these patient cohorts.

Patient satisfaction with the external equipment of implantable left ventricular assist devices.

Patient satisfaction with left ventricular assist device (LVAD) external equipment has not yet been reported. We aimed to evaluate the quality of two different systems based on patients' perspective and its interrelationship with quality of life. Differential assessment of the HeartMate II axial flow pump (n = 17; Thoratec, Pleasanton, CA, USA) and the HVAD centrifugal pump (n = 10; HeartWare, Inc., Miramar, FL, USA) was obtained from 27 outpatients by a questionnaire 2 months to 2.9 years after device implantation. In addition, a health-related quality of life questionnaire (Short Form-36 [SF-36]) was completed. Overall patients' satisfaction was high. Severe limitations were attributed to the loudness of the power base unit in HeartMate II patients (P = 0.00), and HVAD patients were dissatisfied by the length of the driveline (P = 0.02). Between HVAD and HeartMate II patients, no significant differences in the quality of life (assessed by SF-36) were reported. While the overall satisfaction of outpatients on LVAD support was high, differences between the systems were found. Patients' perspectives may have an important impact on future modification of external components. Ultimately, this may also contribute to an improvement in the quality of life of chronic LVAD patients.

Acquired von Willebrand syndrome in patients with an axial flow left ventricular assist device.

BACKGROUND: Rotary blood pumps used as left ventricular assist devices (LVADs) allow for long-term support and may become suitable alternatives to heart transplantation. Effects of this technology on the coagulation system are not completely understood, leading to controversial anticoagulation protocols. Thus, we investigated the primary hemostasis in patients with chronic LVAD therapy. METHODS AND RESULTS: Twenty-six outpatients received axial flow LVAD (HeartMate II; Thoratec) for a median support time of 4.5 months. In a cross-sectional protocol, platelet aggregation in response to ADP and epinephrine, von Willebrand antigen (vWF:AG), and collagen-binding capacity (vWF:CB) were obtained. Von Willebrand factor (vWF) multimer analyses were performed, and patients were screened for bleeding events. This analysis was repeated after removal of the device for transplantation or recovery (n=12) and after a median of 15.5 months in ongoing patients (n=11). In all patients on devices, severe impairment of platelet aggregation as well as a loss of large vWF multimers were found. In 10 patients, a decreased vWF:CB/vWF:AG ratio was observed. Bleeding episodes occurred with an incidence of 0.17 per patient-year. After removal of the device, normal patterns of platelet aggregation, multimer analysis, and vWF:CB/vWF:AG ratio were recorded. In the second analysis of ongoing patients, impairment of platelet aggregation and loss of large vWF multimers were verified. CONCLUSIONS: A diagnosis of von Willebrand syndrome type 2 was established in all patients after LVAD implantation, and bleeding events confirmed this finding. Reversibility of this condition was found after removal of the device.

Health-related quality of life in long-term survivors after heart and lung transplantation: a prospective cohort study.

BACKGROUND: Health-related quality of life (HRQoL) represents an important outcome measure to assess the success of transplantation in the long term. This study evaluated HRQoL in heart (HTx) and lung (LTx) transplant survivors, and assessed potential outcome-related predictors from before to 5 years after transplantation. METHODS: Study participants (n=170) were prospectively followed up from before to 5 years after HTx (n=82) or LTx (n=88), including HRQoL assessments (pretransplantation, 6, 12, and yearly between 24 and 60 months) using the Short Form-36, employment status index, and monitoring of adverse events. RESULTS: Patient groups (HTx vs. LTx) differed with respect to gender (men 74% vs. 48%; P<0.03) and high-urgency waiting status (72% vs. 45%; P<0.0001). Both cohorts showed the most significant HRQoL improvements within the first year posttransplant (P<0.0001), and relatively stable conditions afterward. Marital (P<0.01) and employment status (P<0.01) impacted HRQoL in both groups. The incidence of bronchiolitis obliterans showed significantly lower HRQoL in LTx patients (29.3%; P<0.005). CONCLUSIONS: HTx and LTx patients benefit from the transplant procedure with respect to HRQoL improvements for at least 5 years posttransplant; however, their trajectories during this time interval differ. Further research on organ-type-related predictors of HRQoL is necessary for the development of tailored psychosocial interventions.

The current status of heart transplantation and the development of "artificial heart systems".

BACKGROUND: In view of the major technical advances in ventricular assist devices (VAD) in recent years, the authors discuss the question whether these "artificial hearts" are still no more than a temporary measure for patients awaiting heart transplantation (HTx), or whether they can already be used as an independent form of long-term treatment. METHODS: Statistics from Eurotransplant regarding heart transplantations and transplant waiting lists in Germany are presented. Technical developments in cardiac support systems, the variation in results depending on the indication, and the findings with respect to quality of life are all discussed on the basis of a selective review of the literature and the authors' own clinical experience. RESULTS: The waiting list for heart transplantation in Germany has grown to a record size of nearly 800 patients, while fewer than 400 hearts are transplanted each year. Technical advances have improved outcomes in VAD therapy, but the outcome depends on the patient's preoperative condition. The physical performance of patients who have received VAD is comparable to that of HTx patients; nonetheless, HTx patients have a better quality of life. CONCLUSIONS: Chronic VAD therapy has become a clinical reality. Because of the greater number of patients awaiting HTx, many will not receive their transplants in time. When the decision to treat with VAD is made early, it can be used as an alternative form of treatment with a comparable one-year survival (>75%).

HeartMate II implantation in patients with heparin-induced thrombocytopenia type II.

Diverse anticoagulation protocols are used in patients after implantation of ventricular assist devices. No consensus exists, especially in patients with heparin-induced thrombocytopenia type II. In a patient with heparin-induced thrombocytopenia type II, we implanted a left ventricular assist device (HeartMate XVE; Thoratec, Pleasanton, CA). Thirteen months later the device had to be replaced due to mechanical failure with a HeartMate II left ventricular assist device. We report on our successful protocol of perioperative anticoagulation management using heparin and iloprost during surgery and argatroban thereafter.

Acquired von Willebrand syndrome after exchange of the HeartMate XVE to the HeartMate II ventricular assist device.

Instead of pulsatile ventricular assist devices an increasing number of nonpulsatile ventricular assist devices are introduced to clinical practice. The different flow characteristics of this new technique lead to alteration in shear stress on blood components, which may affect the coagulation system. Repeated von Willebrand factor analyses were performed in a patient who first was implanted with a pulsatile ventricular assist device (Thoratec HeartMate XVE), which had to be replaced after 405 days with an axial flow device (HeartMate II). During support with the pulsatile ventricular assist device there was no sign of any coagulation disorder. However, on the axial flow device acquired von Willebrand syndrome Type 2 developed. Inhibition of platelet function was also observed, which may be in part due to the von Willebrand syndrome. The HeartMate II axial flow device may induce von Willebrand syndrome, which was not observed in HeartMate XVE pulsatile ventricular assist device. Patients put on continuous flow devices should be screened for acquired von Willebrand syndrome.

Implantation of a left ventricular assist device in a patient with primary antiphospholipid syndrome.

The antiphospholipid syndrome is characterized by arterial and venous thrombosis and is associated with the presence of circulating antiphospholipid antibodies. Arterial thrombosis can result in myocardial infarction, which may potentially lead to end-stage heart failure. Here we report our anticoagulation protocol for patients with antiphospholipid syndrome that undergo axial-flow left ventricle assist devices (HeartMate II; Thoratec, Pleasanton, CA) implantation.