Bacteraemia in ventricular assist devices: a common complication that need not affect clinical outcomes.

BACKGROUND: Ventricular assist device (VAD) implantation has become an effective option for patients with severe heart failure. However, device-related infections remain a significant problem. The aim of this study was to describe the incidence and microbiological aetiology of bacteraemia in patients with VADs, and to assess the impact of bacteraemia on clinical outcomes. METHODS: A retrospective study was conducted of patients having VAD implantation at the Alfred Hospital (Melbourne, Australia) from October 1990 to July 2009. Medical records and microbiology databases were reviewed. Patients who were supported with a VAD for 72h or more were evaluated for demographic data, VAD type, the occurrence of bacteraemia and clinical outcomes. RESULTS: During the 19-year period, 135 VAD patients (89 Thoratec PVAD, 10 Novacor, and 36 Ventrassist) supported for a total duration of 17,304 (median 74) support days were included. Sixty-one patients (45%) developed VAD-associated bacteraemia, an incidence of 5.6 episodes per 1000 support days. The incidence of bacteraemia per 1000 days of support was similar for the three devices used: Thoratec PVAD, Novacor and Ventrassist VADs (7.8±0.8, 5.2±1.5 and 3.4±0.5, respectively, p=0.74). Staphylococcus aureus was the most common pathogen (25%). The rates of death on device, survival to transplant, recovery with explant and outcomes after transplantation, including 30-day mortality, median survival time and incidence of cerebrovascular accidents were not significantly impacted upon by bacteraemia. CONCLUSIONS: Bacteraemia is common in VAD patients. However, the incidence of VAD-associated bacteraemia is independent of device type and with aggressive antimicrobial therapy; clinical outcomes need not be affected by the bacteraemia.

Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) Trial: rationale and design.

BACKGROUND: Despite some concern that recent aspirin ingestion increases blood loss after coronary artery surgery, there is some evidence that this may reduce thrombotic complications. In contrast, antifibrinolytic drugs can reduce blood loss in this setting, but there is concern that they may increase thrombotic complications. Published guidelines are limited by a lack of large randomized trials addressing the risks and benefits of each of these commonly used therapies in cardiac surgery. The ATACAS Trial is a study comparing aspirin, tranexamic acid, or both, with placebo in patients undergoing on-pump or off-pump coronary artery surgery. METHODS: We discuss the rationale for conducting ATACAS, a 4600-patient, multicenter randomized trial in at-risk coronary artery surgery, and the features of the ATACAS study design (objectives, end points, target population, allocation, treatments, patient follow-up, and analysis). CONCLUSIONS: The ATACAS Trial will be the largest study yet conducted to ascertain the benefits and risks of aspirin and antifibrinolytic therapy in coronary artery surgery. Results of the trial will guide the routine clinical care of patients in this setting.

First clinical implant of the VentrAssist left ventricular assist system as destination therapy for end-stage heart failure.

The VentrAssist device left ventricular assist system, designed for permanent implantation, is a novel centrifugal pump with a hydrodynamically suspended rotor. The first human implant was into a 72-year-old man with New York Heart Association (NYHA) class IV heart failure due to idiopathic dilated cardiomyopathy. The implant and recovery were uneventful, and the patient survives at 17 months, is NYHA class II, and lives at home. This device shows promise in end-stage heart failure for permanent implantation and bridge to transplantation.

Epstein-Barr virus primary mismatching and HLA matching: key risk factors for post lung transplant lymphoproliferative disease.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) in lung transplant recipients (LTRs) is potentially lethal with considerable morbidity. The role of donor (D)/recipient (R) HLA matching is unknown. METHOD: We reviewed our LTRs from January 1994, when routine D/R Epstein-Barr virus (EBV) serologic screening was begun, through to January 2000. We examined whether D/R HLA match status influenced the risk of PTLD in EBV D+/R- mismatched LTRs. RESULTS: There were 16 D+/R- EBV-mismatched LTRs, 5 (31%) of whom developed PTLD (from a total of 237 LTRs; 218 survived >30 days). There were only two other cases of PTLD among the non-EBV primary mismatched patients. All patients received baseline immunosuppression of cyclosporine, azathioprine, and prednisolone without cytolytics and ganciclovir prophylaxis if "at risk" from cytomegalovirus. The five PTLD cases were diagnosed 81 to 734 (median 116) days from transplantation; three involved the lung allograft and two others involved lymph nodes. All PTLD patients seroconverted for EBV, whereas 7 of the 11 remaining EBV-mismatched patients who did not develop PTLD did not seroconvert. In the 16 EBV primary mismatched patients, there were 4 of 66 HLA allele matches in the 11 PTLD-free patients versus 15 of 30 matches in the 5 PTLD patients (P<0.001). This resulted in 2 or more HLA (A/B/DR) matches in 4 of 5 patients with PTLD versus 0 of 11 in the PTLD-free group (P=0.003). All PTLD patients were treated with reduced immunosuppression and antiviral therapy. Only two of the five LTRs who developed PTLD died, one with progressive disease despite chemotherapy and the other from chronic allograft rejection. CONCLUSION: A high degree of HLA matching in D/R EBV-mismatched LTRs significantly increases the risk of PTLD.

A donor history of smoking affects early but not late outcome in lung transplantation.

BACKGROUND: Liberalization of tobacco exposure history as an exclusion to lung donation has recently occurred to increase donor organ availability. This study investigated the effect of donor smoking status and current and cumulative cigarette dose on early and late outcomes in lung transplantation. METHODS: From 1995 to 2002, 173 heart-lung and bilateral single-lung transplant recipients were retrospectively reviewed. Seventy-seven (45%) of 173 donors were ever-smokers and 64 of those 77 were current smokers. These were divided into subgroups by current number of cigarettes smoked to investigate acute dose effects and by pack-year to investigate cumulative dose effects. Risks of smoking were assessed by univariate and multivariate hazard regression models. RESULTS: Univariate analysis revealed that there were significant differences between current and cumulative dose subgroups in early postoperative variables, including Pao2/Fio2 ratio, ventilation time, and intensive care unit stay. Additionally, these variables were dose dependent. There was no significant difference in 3-year survival between never-smokers and ever-smokers (73% versus 64%, P = 0.27), and a rate of decline of survival was similar. There was a trend for the percentage of patients dying of bronchiolitis obliterans syndrome to be lower in the ever-smokers group compared with the never-smokers group (6% versus 11%, respectively). Multivariate analysis revealed current and cumulative smoking as a risk factor for early but not late outcomes. CONCLUSIONS: Donor smoking history had a significant effect on early outcomes in lung transplantation in a current and cumulative dose-dependent fashion. However, no significant effect on late outcomes, including bronchiolitis obliterans syndrome, was seen.

Donor history of asthma is not a contraindication to lung transplantation: 12-year single-center experience.

BACKGROUND: Donor asthma has been regarded as a contraindication to lung transplantation (LTx) because of concerns that pre-existing airway inflammation will predispose to early and late graft dysfunction. The aim of this study was to describe LTx outcomes in which lungs had been transplanted from donors with a history of asthma. METHODS: A retrospective chart review was undertaken of 743 consecutive donor lung referrals to the Alfred Hospital between 1990 and September 2002. Seventy-four were noted to have a history of asthma, including 18 in whom asthma was the cause of death. Twenty-seven patients became lung donors, of whom 16 were on asthma treatment (on-treatment group) and 11 were not (no-treatment group). RESULTS: From 27 lung donors, 35 LTx procedures were performed (16 double LTx [DLTx], 19 single LTx [SLTx]). Five recipients died at <30 days (including 3 of early graft failure in the no-treatment group), and 7 died at >30 days (only 1 due to BOS). The 30-day, 1-year and 5-year survival rates in the on- and no-treatment donor groups were 90% vs 76%, 74% vs 69% and 74% vs 60%, respectively, and were not significantly different from our overall LTx survival rates. There were no significant differences in percent predicted forced expiratory volume in 1 second, ICU stay or hospital stay overall, or when analyzed according to on treatment vs no treatment and SLTx vs DLTx. Only 2 procedures LTx were performed from fatal asthma donors, both of whom had subsequent graft dysfunction and died on Days 73 and 484, respectively. CONCLUSIONS: The use of lungs from carefully selected lung donors with a history of asthma may increase the donor pool with acceptable long-term outcomes. The use of fatal asthma donors remains problematic.

Occlusive wrap dressing reduces infection rate in saphenous vein harvest site.

BACKGROUND: Infection in the saphenous vein harvest site is a common problem. We developed an occlusive circumferential wrap dressing technique that reduces skin edge tension, eliminates dead space, and prevents external contamination. We compared the surgical site infection rate using the wrap dressing technique with that of standard longitudinal dressings. METHODS. One hundred fifty-two consecutive patients were randomly assigned to receive either standard dressings or the wrap dressing. Data were collected in the hospital and then 4 to 6 weeks postoperatively. Superficial and deep wound infections were defined by the standard criteria from the Centers for Disease Control and Prevention. RESULTS: The infection rate in the wrap group was 14% compared with 35%, for the standard group (p = 0.006). Multivariate analysis showed that wrap technique was the only significant predictor (negative) of infection (odds ratio, 0.19; p = 0.001). CONCLUSIONS: In saphenous vein harvest wounds, the occlusive wrap dressing technique has the potential to reduce the rate of infection by 50%. This simple and inexpensive technique is also readily applicable to the radial artery harvest site in the arm and may provide similar benefit.

Implantation of the VentrAssist Implantable Rotary Blood Pump in sheep.

The VentrAssist Implantable Rotary Blood Pump (IRBP) is a hydrodynamically suspended, electromagnetically driven, centrifugal blood pump that provides continuous flow of up to 10 L/min at 3,000 rpm. In vivo studies in sheep were conducted to assess system design and performance. Surgery involved thoracotomy with subdiaphragmatic pump placement. Cannulae were transdiaphragmatic, with inflow in the left ventricular apex and outflow anastomosed to the descending aorta. Animals had no anticoagulation or antiplatelet therapy after surgery and no prophylactic antibiotics after recovery. Twelve sheep were supported for 622 pump days. Estimated pump flow ranged from 1 to 5.5 L/min at 1,800 to 2,000 rpm using 2.5 to 4.5 W. There was no clinical evidence of hemolysis or cardiovascular, renal, or hepatic dysfunction. Adverse outcomes included kinking/disconnection of the outflow cannula caused by the graft bend relief (n = 4), which was addressed through cannula redesign. Pump electrical malfunction (n = 4), caused by a silicone potting compound, was corrected using a neutral curing potting material. Surgical/husbandry issues (n = 2) also were addressed. The VentrAssist IRBP provides high flow at low rotational speed and power consumption. Further trials are in progress in advance of in vivo studies of the safety and efficacy of the final system.

Heterotopic heart transplant: is there an indication in the continuous flow ventricular assist device era?

OBJECTIVES: Heterotopic heart transplantation (HHTx) is a therapeutic option in heart failure patients with fixed elevated pulmonary hypertension. However, survival is poorer in HHTx recipients, and with improving results in continuous flow ventricular assist devices (VADs), many patients can be bridged to allow normalization of pulmonary artery pressures, making them orthotopic heart transplant (OHTx) candidates. Thus, the aim of this study was to analyse the survival of our HHTx cohort and compare them with our VAD bridge patients. METHODS: A retrospective review of 342 heart transplant patients (315 OHTx and 27 HHTx) performed at our institution over 15 years was compared with 124 bridge-to-transplant VAD patients over the same time period, of whom 69 received an OHTx. Pulmonary artery pressures before and after VAD implant were analysed. Survival was analysed using both univariate and multivariate analyses. RESULTS: HHTx recipients were significantly older, and the donor allografts were older, smaller and had longer ischaemic times than the OHTx cohort. Comparison of the VAD types implanted (pulsatile vs continuous) showed significantly longer time supported on the continuous devices with significantly fewer deaths than the pulsatile devices. The continuous devices were successful in reducing pulmonary artery pressures pretransplant. The HHTx cohort had a significantly poorer survival than the OHTx cohort (P=0.002). Survival on a continuous device and then OHTx was significantly better than either HHTx or pulsatile device support. CONCLUSIONS: The main indication for HHTx, namely fixed elevated pulmonary hypertension in heart failure patients, can be safely and effectively treated by continuous flow bridge to transplant with superior survival.

Extracorporeal membrane oxygenation in primary graft failure after heart transplantation.

BACKGROUND: The aim of this review was to analyze our results with extracorporeal membrane oxygenation (ECMO) support for primary graft failure (PGF) in heart transplant recipients. METHODS: A retrospective review of 239 consecutive patients who underwent heart transplantation between January 2000 and August 2009 was performed. Orthotopic, heterotopic, and heart lung transplants were included in this analysis. Over that time period, 54 patients developed PGF, of whom 39 patients required ECMO support. These 39 patients form the basis of this review. RESULTS: Thirty-four patients (87%) were successfully weaned from ECMO and 29 (74.3%) survived to hospital discharge. There were no significant differences in wean rates or complications between central and peripheral ECMO. Comparison of survival in the 39 ECMO patients to the non-PGF patients (n = 185) showed a significantly worse survival in the ECMO group (p = 0.007). When those patients who died in the first 30 days were excluded, there was no difference in overall survival between groups (p = 0.73). CONCLUSIONS: Extracorporeal membrane oxygenation provides excellent circulatory support for patients with PGF after heart transplantation with good wean and survival to discharge rates.

Initial clinical experience with the VentrAssist left ventricular assist device: the pilot trial.

BACKGROUND: The VentrAssist (VA) is a novel, continuous flow left ventricular assist device (LVAD). The purpose of this trial was to investigate the safety and efficacy of the VA in elderly patients with end-stage heart failure. METHODS: In this prospective trial, patients requiring circulatory support either as destination therapy (DT) or as a bridge to transplant (BTT) were implanted with a VA device. RESULTS: Between June 2003 and August 2006, 9 elderly patients (mean age 65 years) were implanted. The median support time was 454 (range 73 to 977) days for the DT and 35 (range 26 to 508) days for the BTT cohort. All patients survived implantation; 30-day mortality was 22% (n = 2). The adverse event profile was encouraging, with no embolic neurologic events and minimal sepsis. Cumulative trial support time was 7.3 patient-years. CONCLUSIONS: The VentrAssist shows promise as a safe and reliable "third-generation" VAD. Having demonstrated potential as a DT and prolonged BTT device, extended clinical trials are warranted.

Third-time lung transplant using extended criteria lungs.

There is an increasing requirement for lung re-transplants (re-LTx) related to the bronchiolitis obliterans syndrome. Nevertheless, re-LTx, especially second-time re-LTx, poses the dilemma of appropriate allocation of a scarce donor lung resource versus the desire to optimize outcomes for an individual patient. Extended donors have been used to partially alleviate a scarce donor lung supply with satisfactory outcomes for primary lung transplant. However, the usefulness of the extended donors remains unknown, including donation-after-cardiac-death donors for re-LTx. This report describes a second-time re-LTx using significantly extended donor criteria lungs from a Maastricht category IV donation-after-cardiac-death donor with resultant good clinical outcomes.

Prolonged cardiac allograft ischemic time--no impact on long-term survival but at what cost?

INTRODUCTION: The aim of this paper was to review the outcomes of cardiac transplantation with regards to short- and long-term survival, focusing particularly on patients who receive organs with long ischemic times and the resource utilization necessary to support such patients through their postoperative period. METHODS: A retrospective review of 420 consecutive cardiac transplants in a single institution was undertaken. RESULTS: The five- and 10-yr survival rates for the entire group were 0.76 (95% CI: 0.72-0.80) and 0.60 (0.54-0.66). There was no decrease in mid- or long-term survival in patients who received organs with ischemic times over 300 min. Longer donor organ ischemic time was not associated with increased 30 d mortality but was significantly associated with longer intensive care bed stay, increased incidence of primary graft failure, need for mechanical support, and complications such as acute renal failures. CONCLUSIONS: Although using donor organs with longer ischemic times for cardiac transplantation does not impact on survival, there is a significantly increased utilization of resources to ensure these patients survive the postoperative period.

The Alfred Hospital lung transplant experience.

There has been considerable evolution in the pre-, peri- and postoperative management of patients with severe lung disease undergoing LTx. Compared with where we started at the Alfred Hospital in 1990, in 2008 we now recognize that the majority of donor lungs that are offered for LTx (including DCD lungs) are useable, patients with a wide range of ages and disease processes are suitable to be considered for LTx and modern surgical, anesthetic and ICU management should result in a 90% one-year survival rate. It is likely that the procedural mix in LTX servicing will remain little changed in the years to come, with BLTx being the pre-eminent service modality for the majority of end-stage lung disease patients. SLTx will remain a viable procedure almost exclusively for the IPF recipient, with HLTx a necessity for the congenital heart disease patient, for whom all other medical and surgical options have been exhausted. Notwithstanding theseconsiderable achievements, including the factthat one-third of patients now survive more than10 years, it is also apparent that BOS and recurrent infections remain a problem limiting the overall success of LTx. Understanding more about the interactions between the immunosuppressive regimen, infective agents (particularly viruses) and the recipients responses to all of the abovehold the keys to improving these late outcomes.

The split radial technique: an alternative to the Y-graft for total arterial myocardial revascularisation.

There is evidence that the use of Y-grafts attached to the left internal mammary artery - to - left anterior descending artery graft may compromise the patency of the distal limb of the left internal mammary artery. We describe a technique (split radial technique) that avoids the use of Y-grafts by constructing two aorto-coronary grafts from a single radial artery. The split radial technique requires the harvesting of the radial artery in its entirety from the brachial bifurcation to the radial styloid. The first radial artery distal anastomosis is performed and the required length of conduit is determined. The conduit is transected, leaving a sufficiently long radial segment for a second aorto-coronary graft. A clinical follow-up 41 weeks after surgery of the first 37 patients in whom the split radial technique was used showed no deaths or major complications. This suggests that the split radial technique is a useful and safe way to maximise the use of radial artery conduit and to avoid the potential risk of compromising internal mammary artery patency with Y-grafts. There is evidence that the use of Y-grafts attached to the left internal mammary artery may compromise the patency of the distal limb of the left internal mammary artery. We describe the split radial technique of constructing two aorto-coronary graft segments from a single radial artery that can be used to avoid the use of Y-grafts.

Early institution of mechanical support improves outcomes in primary cardiac allograft failure.

BACKGROUND: Primary graft failure (PGF) is the leading cause of early mortality after cardiac transplantation, accounting for 27.1% of deaths within 30 days. PGF is defined as severe dysfunction of the cardiac allograft without any obvious anatomic or immunological cause. The purpose of this study was to analyze our last 9 years of experience with cardiac transplantation to determine predictors of PGF and the influence on survival of our policy of early institution of mechanical circulatory support (MCS) in these patients. METHODS: Data on 214 consecutive cardiac transplants performed at The Alfred Hospital between January 1996 and August 2004 were reviewed. PGF was defined as right or left or biventricular failure manifesting as hypotension (systolic blood pressure <90 mm Hg), low cardiac output (cardiac index <2.0 liter/min/m2 and pulmonary capillary wedge pressure >20 mm Hg after coming off cardiopulmonary bypass despite inotropic support of up to 5 mug/min adrenaline and without any other obvious cause for the graft dysfunction. RESULTS: PGF developed in 51 patients (24%). Significant factors in the development of PGF were long ischemic time, which became significant over 4 hours (odds ratio, 1.43; p = 0.01) and increased donor age (odds ratio, 1.027; p = 0.045). Fifteen patients required mechanical support, and of these, 10 survived to leave hospital. CONCLUSIONS: PGF is the major cause of early mortality after cardiac transplantation. Significant risks for PGF are long allograft ischemic time and increased donor age. Once the patient has survived 30 days, however, the longer-term survival is not influenced by PGF. Our management strategy of early mechanical support has yielded good outcomes in this population with a high risk of early death.

Unexpected donor pulmonary embolism affects early outcomes after lung transplantation: a major mechanism of primary graft failure?

OBJECTIVE: Primary graft failure remains a significant cause of morbidity and mortality after lung transplantation, and its mechanism is not understood. Previously 2 case reports described fatal primary graft failure due to donor-related unexpected pulmonary embolism. This study investigated the incidence, early outcome, and risk factors of unexpected pulmonary embolism in lung transplantation. METHODS: An exploratory retrograde donor lung flush before implantation to diagnose pulmonary embolism (emboli group) or no pulmonary embolism (no-emboli group) was performed in 74 of 122 consecutive lung transplantations. RESULTS: The incidence of macroscopic unexpected pulmonary embolism was 38% (28% clot and 9% fat). In the emboli group, significantly decreased oxygenation (P < .05), increased pulmonary vascular resistance (P < .001), an increased proportion of opacity on chest radiograph (P = .03), prolonged intubation (P < .001) and intensive care unit stay (P < .01), and decreased 1-year survival (P = .03) were seen after transplantation. In multivariate analysis, pulmonary embolism was an independent risk factor for prolonged intubation (hazard ratio, 2.42; P < .01). In logistic regression, death due to trauma with fracture and a smoking history of more than 20 pack-years were significant donor risk factors for pulmonary embolism (adjusted odds ratio, 8.77 and 5.64; P = .02 and .04, respectively). No deleterious effects of the exploratory flush were seen. CONCLUSIONS: Unexpected pulmonary embolism is relatively common, is potentially predicted by donor history (but not by arterial blood gas analysis or chest radiograph), and is associated with primary graft failure. Donor lungs with risk factors of pulmonary embolism should undergo an exploratory flush. When pulmonary embolism is diagnosed, further therapeutic strategies must be considered.