Twelve-hour reanimation of a human heart following donation after circulatory death.

Despite increasing use of donation after cardiac death (DCD) and encouraging results for non-cardiac transplants, DCD cardiac transplantation has not been widely adopted because, (1) the DCD heart sustains warm ischaemic injury during the death process and (2) conventional static cold storage significantly adds to the ischaemic injury. We have developed a simple system for perfusion of the DCD heart with cold crystalloid solution using gravity-feed that can reduce ischaemic injury and potentially render the heart suitable for transplantation. This report describes the first application of this technique to a human DCD heart with good functional metabolic recovery over 12h on an ex vivo rig.

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.

Ventricular assist device infections.

Ventricular Assist Devices(VAD) are the commonest form of cardiac mechanical support, used as bridge to transplantation but also as destination therapy in non-transplant-eligible patients in whom transplantation is considered unsuitable based on age criteria. Infections are common and can significantly impact on patient outcome. Strategies to prevent and treat infections have not been assessed by randomised controlled trials, a difficult task due to the multiplicity of devices and their ongoing evolution. This review summarises the recent literature on infections in VAD-supported patients, including the recently proposed definitions, microbiology, diagnosis, treatment and preventive strategies.

Physical conditioning and mental stress reduction--a randomised trial in patients undergoing cardiac surgery.

BACKGROUND: Preoperative anxiety and physical unfitness have been shown to have adverse effects on recovery from cardiac surgery. This study involving cardiac surgery patients was primarily aimed at assessing the feasibility of delivering physical conditioning and stress reduction programs within the public hospital setting. Secondary aims were to evaluate the effect of these programs on quality of life (QOL), rates of postoperative atrial fibrillation (AF) and length of stay (LOS) in hospital. METHODS: Elective patients scheduled for coronary artery bypass graft and/or valve surgery at a public hospital in Melbourne, Australia were enrolled. Patients were randomized to receive either holistic therapy (HT) or usual care (UC). HT consisted of a series of light physical exercise sessions together with a mental stress reduction program administered in an outpatient setting for the first two weeks after placement on the waiting list for surgery. A self-administered SF-36 questionnaire was used to measure QOL and hospital records to collect data on LOS and rate of postoperative AF. RESULTS: The study population comprised 117 patients of whom 60 received HT and 57 received UC. Both programs were able to be delivered within the hospital setting but ongoing therapy beyond the two week duration of the program was not carried out due to long waiting periods and insufficient resources. HT, as delivered in this study, compared to UC did not result in significant changes in QOL, LOS or AF incidence. CONCLUSIONS: Preoperative holistic therapy can be delivered in the hospital setting, although two weeks is insufficient to provide benefits beyond usual care on QOL, LOS or postoperative AF. Further research is now required to determine whether a similar program of longer duration, or targeted to high risk patients can provide measurable benefits. TRIAL REGISTRATION: This trial was conducted as part of a larger study and according to the principles contained in the CONSORT statement 2001.

Perioperative metabolic therapy improves redox status and outcomes in cardiac surgery patients: a randomised trial.

OBJECTIVE: Perioperative therapy with antioxidants and metabolic substrates has the potential to reduce oxidative stress and improve recovery from cardiac surgery, particularly in elderly and high risk cases. The aim of this study was to assess the effect of perioperative metabolic therapy at a biochemical, clinical and economic level in cardiac surgical patients. METHODS: Patients (n=117, mean age 65 ± 1.0 years, 74% male) undergoing elective coronary artery bypass graft (CABG) and/or valve surgery in 2004-2006 were randomised to receive in double blinded fashion, while on the waiting list for surgery (approximately two months) and one month after surgery, either metabolic therapy (coenzyme Q(10), magnesium orotate, lipoic acid, omega-3 fatty acids and selenium) or placebo. Biochemical and clinical outcomes were assessed. RESULTS: Cardiac surgery increased oxidative stress and decreased plasma levels of key antioxidants. Metabolic therapy for a mean of 76 ± 7.5 days increased antioxidant levels preoperatively so that the adverse effect of surgery on redox status was attenuated. Metabolic therapy reduced plasma troponin I, 24 hours postoperatively from 1.5 (1.2-1.8) (geometric mean 95% CI) µg/L, to 2.1 (1.8-2.6) µg/L (P=0.003) and shortened the mean length of postoperative hospital stay by 1.2 days from 8.1 (7.5-8.7) to 6.9 (6.4-7.4) days (P=0.004) and reduced hospital costs. Metabolic therapy was inexpensive and had no clinically significant side effects. CONCLUSIONS: Perioperative metabolic therapy for cardiac surgery is safe and inexpensive and is associated with improved redox status, reduced myocardial damage, and shortened length of postoperative hospital stay.

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.

VentrAssist left ventricular assist device: clinical trial results and Clinical Development Plan update.

OBJECTIVES: To summarise the primary efficacy and safety results from the first international clinical trial with the VentrAssist left ventricular assist device and to provide an update on the VentrAssisttrade mark Clinical Development Plan. METHODS: The first prospective, single-arm, multicentre international clinical trial with the VentrAssist in bridge-to-transplant patients (CE Mark trial) was conducted in Australia, UK and Norway between 2004 and 2006. The primary outcome measure was survival until transplant or being transplant-eligible at postoperative day 154. The number and status of other clinical trials in the VentrAssist Clinical Development Plan are also described. RESULTS: At the completion of the CE Mark trial, 25 of the 30 patients (83%) were transplanted or transplant-eligible. There were no unexpected safety issues and no reported uncontrolled stops of the VentrAssist pump. The Clinical Development Plan for the VentrAssist currently comprises seven clinical trials: two are completed, three are ongoing and two are ready for initiation. As of January 30th, 2007, a total of 87 patients have been implanted with the VentrAssist at 14 centres worldwide, yielding a total exposure time of more than 43 patient-years and a maximum implant duration of 2.7 years. CONCLUSIONS: The efficacy and safety data from a clinical trial of the VentrAssist were favourable and resulted in gaining European regulatory approval for this indication. Notably, the survival success rate for the VentrAssist was higher than that reported for other left ventricular assist devices. The overall number of implants with the VentrAssist has now surpassed that of any other third-generation centrifugal device.

A novel combination technique of cold crystalloid perfusion but not cold storage facilitates transplantation of canine hearts donated after circulatory death.

BACKGROUND: Donation after circulatory death (DCD) represents a potential new source of hearts to increase the donor pool. We showed previously that DCD hearts in Greyhound dogs could be resuscitated and preserved by continuous cold crystalloid perfusion but not by cold static storage and could demonstrate excellent contractile and metabolic function on an in vitro system. In the current study, we demonstrate that resuscitated DCD hearts are transplantable. METHODS: Donor Greyhound dogs (n = 12) were divided into perfusion (n = 8) and cold static storage (n = 4) groups. General anesthesia was induced and ventilation ceased for 30 minutes to achieve circulatory death. Donor cardiectomy was performed, and for 4 hours the heart was preserved by controlled reperfusion, followed by continuous cold perfusion with an oxygenated crystalloid perfusate or by static cold storage, after which orthotopic heart transplantation was performed. Recovery was assessed over 4 hours by hemodynamic monitoring. RESULTS: During cold perfusion, hearts showed continuous oxygen consumption and low lactate levels, indicating aerobic metabolism. The 8 dogs in the perfusion group were weaned off bypass, and 4 hours after bypass produced cardiac output of 4.73 ± 0.51 liters/min, left ventricular power of 7.63 ± 1.32 J/s, right ventricular power of 1.40 ± 0.43 J/s, and left ventricular fractional area shortening of 39.1% ± 5.2%, all comparable to pre-transplant values. In the cold storage group, 3 of 4 animals could not be weaned from cardiopulmonary bypass, and the fourth exhibited low-level function. CONCLUSIONS: Cold crystalloid perfusion, but not cold static storage, can resuscitate and preserve the DCD donor heart in a canine model of heart transplantation, thus rendering it transplantable. Controlled reperfusion and cold crystalloid perfusion have potential for clinical application in DCD transplantation.

Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue.

OBJECTIVES: Previous clinical trials suggest that coenzyme Q(10) might afford myocardial protection during cardiac surgery. We sought to measure the effect of coenzyme Q(10) therapy on coenzyme Q(10) levels in serum, atrial trabeculae, and mitochondria; to assess the effect of coenzyme Q(10) on mitochondrial function; to test the effect of coenzyme Q(10) in protecting cardiac myocardium against a standard hypoxia-reoxygentation stress in vitro; and to determine whether coenzyme Q(10) therapy improves recovery of the heart after cardiac surgery. METHODS: Patients undergoing elective cardiac surgery were randomized to receive oral coenzyme Q(10) (300 mg/d) or placebo for 2 weeks preoperatively. Pectinate trabeculae from right atrial appendages were excised, and mitochondria were isolated and studied. Trabeculae were subjected to 30 minutes of hypoxia, and contractile recovery was measured. Postoperative cardiac function and troponin I release were assessed. RESULTS: Patients receiving coenzyme Q(10) (n = 62) had increased coenzyme Q(10) levels in serum (P = .001), atrial trabeculae (P = .0001), and isolated mitochondria (P = .0002) compared with levels seen in patients receiving placebo (n = 59). Mitochondrial respiration (adenosine diphosphate/oxygen ratio) was more efficient (P = .012), and mitochondrial malondialdehyde content was lower (P = .002) with coenzyme Q(10) than with placebo. After 30 minutes of hypoxia in vitro, pectinate trabeculae isolated from patients receiving coenzyme Q(10) exhibited a greater recovery of developed force compared with those in patients receiving placebo (46.3% +/- 4.3% vs 64.0% +/- 2.9%, P = .001). There was no between-treatment difference in preoperative or postoperative hemodynamics or in release of troponin I. CONCLUSIONS: Preoperative oral coenzyme Q(10) therapy in patients undergoing cardiac surgery increases myocardial and cardiac mitochondrial coenzyme Q(10) levels, improves mitochondrial efficiency, and increases myocardial tolerance to in vitro hypoxia-reoxygenation stress.

Left ventricular apical infection and rupture complicating left ventricular assist device explantation in 2 women with postpartum cardiomyopathy.

Postpartum cardiomyopathy is rare form of cardiac failure, with the potential for cardiac function to recover to normal. When medical therapy fails to control symptoms or haemodynamic stability, circulatory support with a ventricular assist device may be considered as a bridge to cardiac transplantation. We describe 2 patients with severe postpartum cardiomyopathy, in whom cardiac function recovered sufficiently during mechanical circulatory assistance to enable device explantation. Bacteremia during device support was treated with chronic suppressive antibiotics, yet after cannula explantation and ventricular repair, residual infection led to destruction of the primary repair, with formation of a left ventricular pseudoaneurysm. This is a complication of device support not previously reported. Surgery was necessary to repair the infected ventricular cannula site. Both patients recovered; however one patient developed recurrent cardiomyopathy 4 months later.

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.

Cardiac tamponade due to coronary artery erosion.

This report describes two patients with cardiac tamponade secondary to bleeding from a coronary artery, which had been eroded by a foreign body. In one patient the foreign body had been ingested and in the other patient, the cause was iatrogenic. This report highlights varied and unusual causes of cardiac tamponade.

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.

Coenzyme Q10 protects the aging heart against stress: studies in rats, human tissues, and patients.

With aging of the population, increasing numbers of elderly patients are presenting for cardiac surgery. However, the results in the elderly are inferior to those in the young. A likely contributing factor is an age-related reduction in cellular energy production in the myocardium during surgery, which is known to induce aerobic and ischemic stress. The lipophilic antioxidant and mitochondrial respiratory chain redox coupler, coenzyme Q10 (CoQ10), has the potential to improve energy production in mitochondria by bypassing defective components in the respiratory chain as well as by reducing the effects of oxidative stress. We hypothesized that CoQ10 pretreatment prior to stress could improve the recovery of the myocardium after stress.

A novel method for performing sequential grafts with the radial artery.

We describe a novel technique for the construction of radial artery sequential grafts. By using a 2.7-mm aortic hole punch in the radial artery we are able to form a circular arteriotomy. This allows greater flexibility with orientation of the sequential anastomosis and potentially a wider-open anastomosis. It also avoids the problem of picking up the back wall of this often thick-walled muscular artery given the better visibility afforded by the technique.

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.