Developing and validating a new national remote health advice syndromic surveillance system in England.

Background: Public Health England (PHE) coordinates a suite of real-time national syndromic surveillance systems monitoring general practice, emergency department and remote health advice data. We describe the development and informal evaluation of a new syndromic surveillance system using NHS 111 remote health advice data. Methods: NHS 111 syndromic indicators were monitored daily at national and local level. Statistical models were applied to daily data to identify significant exceedances; statistical baselines were developed for each syndrome and area using a multi-level hierarchical mixed effects model. Results: Between November 2013 and October 2014, there were on average 19 095 NHS 111 calls each weekday and 43 084 each weekend day in the PHE dataset. There was a predominance of females using the service (57%); highest percentage of calls received was in the age group 1-4 years (14%). This system was used to monitor respiratory and gastrointestinal infections over the winter of 2013-14, the potential public health impact of severe flooding across parts of southern England and poor air quality episodes across England in April 2014. Conclusions: This new system complements and supplements the existing PHE syndromic surveillance systems and is now integrated into the routine daily processes that form this national syndromic surveillance service.

Physiologic Changes in the Heart Following Cessation of Mechanical Ventilation in a Porcine Model of Donation After Circulatory Death: Implications for Cardiac Transplantation.

Hearts donated following circulatory death (DCD) may represent an additional source of organs for transplantation; however, the impact of donor extubation on the DCD heart has not been well characterized. We sought to describe the physiologic changes that occur following withdrawal of life-sustaining therapy (WLST) in a porcine model of DCD. Physiologic changes were monitored continuously for 20 min following WLST. Ventricular pressure, volume, and function were recorded using a conductance catheter placed into the right (N = 8) and left (N = 8) ventricles, and using magnetic resonance imaging (MRI, N = 3). Hypoxic pulmonary vasoconstriction occurred following WLST, and was associated with distension of the right ventricle (RV) and reduced cardiac output. A 120-fold increase in epinephrine was subsequently observed that produced a transient hyperdynamic phase; however, progressive RV distension developed during this time. Circulatory arrest occurred 7.6±0.3 min following WLST, at which time MRI demonstrated an 18±7% increase in RV volume and a 12±9% decrease in left ventricular volume compared to baseline. We conclude that hypoxic pulmonary vasoconstriction and a profound catecholamine surge occur following WLST that result in distension of the RV. These changes have important implications on the resuscitation, preservation, and evaluation of DCD hearts prior to transplantation.

A trans-Atlantic examination of haddock Melanogrammus aeglefinus food habits.

The food habits of Melanogrammus aeglefinus were explored and contrasted across multiple north-eastern and north-western Atlantic Ocean ecosystems, using databases that span multiple decades. The results show that among all ecosystems, echinoderms are a consistent part of M. aeglefinus diet, but patterns emerge regarding where and when M. aeglefinus primarily eat fishes v. echinoderms. Melanogrammus aeglefinus does not regularly exhibit the increase in piscivory with ontogeny that other gadoids often show, and in several ecosystems there is a lower occurrence of piscivory. There is an apparent inverse relationship between the consumption of fishes and echinoderms in M. aeglefinus over time, where certain years show high levels of one prey item and low levels of the other. This apparent binary choice can be viewed as part of a gradient of prey options, contingent upon a suite of factors external to M. aeglefinus dynamics. The energetic consequences of this prey choice are discussed, noting that in some instances it may not be a choice at all.

Internet-based remote health self-checker symptom data as an adjuvant to a national syndromic surveillance system.

Syndromic surveillance is an innovative surveillance tool used to support national surveillance programmes. Recent advances in the use of internet-based health data have demonstrated the potential usefulness of these health data; however, there have been limited studies comparing these innovative health data to existing established syndromic surveillance systems. We conducted a retrospective observational study to assess the usefulness of a national internet-based 'symptom checker' service for use as a syndromic surveillance system. NHS Direct online data were extracted for 1 August 2012 to 1 July 2013; a time-series analysis on the symptom categories self-reported by online users was undertaken and compared to existing telehealth syndromic data. There were 3·37 million online users of the internet-based self-checker compared to 1·43 million callers to the telephone triage health service. There was a good correlation between the online and telephone triage data for a number of syndromic indicators including cold/flu, difficulty breathing and eye problems; however, online data appeared to provide additional early warning over telephone triage health data. This assessment has illustrated some potential benefit of using internet-based symptom-checker data and provides the basis for further investigating how these data can be incorporated into national syndromic surveillance programmes.

THE PAPWORTH PLUG - successful use of high dose fibrinogen concentrate and platelet concentrate in potential life-threatening complication after cardiopulmonary bypass surgery in a patient with Type 2M Vicenza von Willebrand Disease.

Anecdotally, fibrinogen concentrate (FC) has been used as a "universal" haemostatic agent in complex post-cardiopulmonary bypass (CPB) coagulopathy. We present a case where FC and two pools of platelets prevented life-threatening bleeding in a patient with moderate von Willebrand Disease (vWD) immediately post CPB.

Ex vivo perfusion of the swine heart as a method for pre-transplant assessment.

We describe a cost-effective, reproducible circuit in a porcine, ex vivo, continuous warm-blood, bi-ventricular, working heart model that has future possibilities for pre-transplant assessment of marginal hearts donated from brain stem dead donors and hearts donated after circulatory determination of death (DCDD). In five consecutive experiments over five days, pressure volume loops were performed. During working mode, the left ventricular end systolic pressure volume relationship (LV ESPVR) was 23.1±11.1 mmHg/ml and the LV preload recruitable stroke work (PRSW) was 67.8±7.2. (Standard PVAN analysis software) (Millar Instruments, Houston, TX, USA) All five hearts were perfused for 219±64 minutes and regained normal cardiac function on the perfusion system.They displayed a significant upward and leftward shift of the end systolic pressure volume relationship, a significant increase in preload recruitable stroke work and minimal stiffness. These hearts could potentially be considered for transplantation. The circuit was effective during reperfusion and working modes whilst proving to be successful in maintaining cardiac function in excess of four hours. Using an autologous prime of approximately 20% haematocrit (Hct), electrolytes and blood gases were easy to control within this period using standard perfusion techniques.

Hearts from DCD donors display acceptable biventricular function after heart transplantation in pigs.

Cardiac transplantation is in decline, in contrast to other solid organs where the number of solid organ transplants from donors after circulatory death (DCD) is increasing. Hearts from DCD donors are not currently utilized due to concerns that they may suffer irreversible cardiac injury with resultant poor graft function. Using a large animal model, we tested the hypothesis that hearts from DCD donors would be suitable for transplantation. Donor pigs were subjected to hypoxic cardiac arrest (DCD) followed by 15 min of warm ischemia and resuscitation on cardiopulmonary bypass, or brainstem death (BSD) via intracerebral balloon inflation. Cardiac function was assessed through load-independent measures and magnetic resonance imaging and spectroscopy. After resuscitation, DCD hearts had near normal contractility, although stroke volume was reduced, comparable to BSD hearts. DCD hearts had a significant decline in phosphocreatine and increase in inorganic phosphate during the hypoxic period, with a return to baseline levels after reperfusion. After transplantation, cardiac function was comparable between BSD and DCD groups. Therefore, in a large animal model, the DCD heart maintains viability and recovers function similar to that of the BSD heart and may be suitable for clinical transplantation. Further study is warranted on optimal reperfusion strategies.

Value of syndromic surveillance in monitoring a focal waterborne outbreak due to an unusual Cryptosporidium genotype in Northamptonshire, United Kingdom, June - July 2008.

The United Kingdom (UK) has several national syndromic surveillance systems. The Health Protection Agency (HPA)/NHS Direct syndromic surveillance system uses pre-diagnostic syndromic data from a national telephone helpline, while the HPA/QSurveillance national surveillance system uses clinical diagnosis data extracted from general practitioner (GP)-based clinical information systems. Data from both of these systems were used to monitor a local outbreak of cryptosporidiosis that occurred following Cryptosporidium oocyst contamination of drinking water supplied from the Pitsford Reservoir in Northamptonshire, United Kingdom, in June 2008. There was a peak in the number of calls to NHS Direct concerning diarrhoea that coincided with the incident. QSurveillance data for the local areas affected by the outbreak showed a significant increase in GP consultations for diarrhoea and gastroenteritis in the week of the incident but there was no increase in consultations for vomiting. A total of 33 clinical cases of cryptosporidiosis were identified in the outbreak investigation, of which 23 were confirmed as infected with the outbreak strain. However, QSurveillance data suggest that there were an estimated 422 excess diarrhoea cases during the outbreak, an increase of about 25% over baseline weekly levels. To our knowledge, this is the first time that data from a syndromic surveillance system, the HPA/QSurveillance national surveillance system, have been able to show the extent of such a small outbreak at a local level. QSurveillance, which covers about 38% of the UK population, is currently the only GP database that is able to provide data at local health district (primary care trust) level. The Cryptosporidium contamination incident described demonstrates the potential usefulness of this information, as it is unusual for syndromic surveillance systems to be able to help monitor such a small-scale outbreak.

Aortic valve replacement for late infective endocarditis after heart-lung transplantation.

Infective endocarditis is a rare but life-threatening complication of heart and heart-lung transplantation. We describe a 32-year-old woman who developed aortic valvular endocarditis following heart-lung transplantation. Enterococcus was the infective organism. The patient's condition was successfully managed using prolonged intravenous antibiotic therapy and aortic valve replacement.

A study of urgent and emergency referrals from NHS Direct within England.

OBJECTIVES: The presented study aimed to explore referral patterns of National Health Service (NHS) Direct to determine how patients engage with telephone-based healthcare and how telephone-based healthcare can manage urgent and emergency care. SETTING: NHS Direct, England, UK PARTICIPANTS: NHS Direct anonymised call data (N=1,415,472) were extracted over a representative 1-year period, during the combined month periods of July 2010, October 2010, January 2011 and April 2011. Urgent and emergency calls (N=269,558; 19.0%) were analysed by call factors and patient characteristics alongside symptom classification. Categorical data were analysed using the χ(2) test of independence with cross-tabulations used to test within-group differences. PRIMARY AND SECONDARY OUTCOME MEASURES: Urgent and emergency referrals to 999; accident and emergency or to see a general practitioner urgently, which are expressed as call rate per 100 persons per annum. Outcomes related to symptom variations by patient characteristics (age, gender, ethnicity and deprivation) alongside differences by patient characteristics of call factors (date and time of day). RESULTS: Urgent and emergency referrals varied by a range of factors relating to call, patient and symptom characteristics. For young children (0-4), symptoms related to 'crying' and 'colds and flu' and 'body temperature change' represented the significantly highest referrals to 'urgent and emergency' health services symptoms relating to 'mental health' alongside 'pain' and 'sensation disorders' represented the highest referrals to urgent and emergency health services for adults aged 40+ years. CONCLUSIONS: This study has highlighted characteristics of 'higher likelihood' referrals to urgent and emergency care through the delivery of a national nurse-led telephone healthcare service. This research can help facilitate an understanding of how patients engage with both in and out of hours care and the role of telephone-based healthcare within the care pathway.

Analysis of four tylosin biosynthetic genes from the tylLM region of the Streptomyces fradiae genome.

The tylLM region of the tylosin biosynthetic gene cluster of Streptomyces fradiae contains four open reading frames (orfs1*-4*). The function of the orf1* product is not known. The product of orf2* (tylM2) is the glycosyltransferase that adds mycaminose to the 5-hydroxyl group of tylactone, the polyketide aglycone of tylosin (Ty). A methyltransferase, responsible for 3-N-methylation during mycaminose production, is encoded by orf3* (tylM1). The product of orf4* (cer) is crotonyl-CoA reductase, which converts acetoacetyl-CoA to butyryl-CoA for use as a 4C extender unit during tylactone production.

Risk factor analysis for the major hazards following heart transplantation--rejection, infection, and coronary occlusive disease.

This study demonstrates the importance of analyzing survival by cause of death in order to achieve a better understanding of the prognostic indicators involved. It further emphasizes the need for analysis of risk factors in both univariate and multivariate models, and the danger of making judgements based on premature analysis of data on follow-up after heart transplantation. Survival following transplantation is characterized by the major hazards of early death due to infection and rejection and late graft loss due to coronary occlusive disease (COD). This study summarizes the first-graft survival experience for 323 transplant patients at Papworth Hospital, and assesses a number of potential risk factors for (1) early mortality, (2) late mortality from COD, and (3) development of COD. The potential risk factors considered for all hazards are donor and recipient age, sex, blood group, and matching of these factors; donor cause of death and recipient immunosuppression; inotropic support; waiting time; preoperative diagnosis and previous cardiac surgery; ischemic time; and extubation time. In addition, for development of, and graft loss from, COD, perioperative rejection and cytomegalovirus infection; hypertension at discharge; and cholesterol, triglycerides, and lipids at two years were assessed as risk factors. Advances in immunosuppression were observed to have increased overall survival rates and decreased mortality from infection, rejection, and COD, as well as decreasing morbidity from COD. Fatal rejection was found to be more likely in female recipients, recipients over 40 years, recipients of grafts from donors over 30 years old, patients who were transplanted for valvular heart disease, and patients who waited less than three months for their transplant. Male recipients of female donor organs were more likely to lose their grafts as a result of COD. Patients older than 50 and hearts from donors older than 40 conferred a high risk of development of and loss from COD. Patients transplanted for ischemic heart disease were more likely to develop COD. High cholesterol, low HDL, high LDL, and high triglycerides at two years after transplant showed some evidence of high risk for the subsequent development of COD, although these relationships are not statistically significant at this stage. Contrary to other recent studies, cytomegalovirus infection was not found to be a risk factor for the development of COD.

Risk factors for survival following combined heart-lung transplantation. The first 100 patients.

As the numbers of heart and lung transplant recipients have increased it has become possible to identify major risk factors for early (within 3 months) and later (after 3 months) death after this procedure. For 100 patients receiving organs between April 1984 and February 1991, and followed up until February 1992, patient characteristics, operative details, and early morbidity were assessed for their effects on early and later deaths. Recipient age, sex, and preoperative diagnosis did not have a significant effect on early (within 3 months) or later death. Positive cytomegalovirus antibody status of donor or recipient conferred greater risk of death within 90 days (odds ratio [OR] = 3.24, P = 0.06). Greater than 2 L blood in the first 24 hr after operation (OR = 6.00, P = 0.05), and ventilation for greater than 24 hr (OR = 4.87, P = 0.006) were significant prognostic indicators of early death. After the first 3 months, the main risk factor for death was rejection in the first 3 months (OR = 1.38 per episode, P = 0.008). Early infection in general and CMV infection in particular were associated with a small increase in risk. This study confirms the importance of matching donor and recipient for CMV and shows that difficulties during operation, reflected in postoperative bleeding and ventilation times increased the chance of early death. Later death was associated with early acute rejection. A detrimental effect of infection, including CMV infection, either does not exist, or is too small to be detected in a study of this size.

Human leukocyte antigen compatibility in heart transplantation: evidence for a differential role of HLA matching on short- and medium-term patient survival.

BACKGROUND: Studies of the influence of human leukocyte antigen (HLA) matching on cardiac transplant outcome have proved inconclusive, mainly due to the lack of well-matched grafts. However, a growing number of studies report improved clinical course and patient survival in cases with increased HLA compatibility. Opelz et al. believe these benefits justify the introduction of prospective HLA-matching strategies. METHODS: We performed univariate and multivariate analyses to examine the short- and medium-term influence of HLA matching on 556 consecutive primary heart transplants performed at a single center between 1983 and 1994. Overall graft survival at 1, 3, and 5 years was 80%, 74%, and 67% respectively. Sixteen (2.9%) grafts failed within 5 days and were not considered in the analysis of the HLA matching and graft survival data. RESULTS: Complete HLA-A, -B, and -DR typing data were available on 477 transplant pairs. The results demonstrate a 12% 1-year survival advantage for 31 patients with zero to two HLA antigen mismatches compared with three to six mismatches. The influence of each individual locus was 6.1%, 8.4%, and 5.4% for zero HLA-A, -B, and -DR mismatches, respectively, compared with two mismatches. However, when outcome from 1 to 5 years was considered, analysis of the role of each locus revealed marked differences. HLAA-matched grafts (n=45) had a 24% lower survival rate compared with two-antigen-mismatched grafts (n=148; 88% [SE 3.1] vs. 64% [SE 8.2], respectively; P=0.009). Furthermore, 34% of HLA-A-matched grafts failed between 1 and 5 years, compared with only 5% of HLA-B-matched grafts (P=0.013). CONCLUSIONS: These data suggest that although HLA matching is effective at reducing acute graft loss, in the longer term, HLA-A matching may impair survival. HLA-A may serve as a restriction element for indirect presentation of allopeptides or tissue-specific minor histocompatibility antigens, facilitating chronic graft loss. Therefore, we advocate a differential role for HLA matching over two epochs. A blanket approach to prospective matching for heart transplants may be premature for optimal long-term survival.

Randomized trial of blood eosinophil count monitoring as a guide to corticosteroid dosage adjustment after heart transplantation.

BACKGROUND: Increases in blood eosinophil counts (EOS) beyond 0.06 x 10(9)/liter precede treated heart allograft rejection. An oral prednisolone dose of 0.35 mg/kg/day usually suppresses EOS below this threshold. METHODS: We designed a randomized trial to compare our empirical protocol for steroid dose adjustment with a novel protocol guided by EOS monitoring during the first 3 months after heart transplantation. Eighty patients were randomized to either have their EOS reported and used for steroid dose adjustment (RG; n=40), or not reported (NG; n=40). RG patients had their steroid dosage increased if EOS exceeded 0.06 x 10(9)/liter. RESULTS: RG patients had an 83% lower risk of treated rejection (P=0.035) and lower median intravenous dose of methyl-prednisolone (P=0.017) than NG during the first 6 postoperative weeks. The proportion of diagnostic increases in EOS that were followed within 2 weeks by treated rejection was 42% greater in NG than RG (P=0.0001), compatible with a direct impact of EOS-guided prednisolone dose adjustment on the risk of subsequent rejection. Overall, RG had less than half the risk of rejection of any grade (P<0.001) and significantly more rejection-free biopsies than NG (P=0.001). The mean oral prednisolone dosage was significantly greater in RG than NG during the first (P=0.014) and second (P=0.001) 6 weeks of follow-up. This did not increase the incidence of serious steroid-related side effects. CONCLUSIONS: EOS monitoring is a simple, cheap, and effective means of optimizing steroid immunosuppression. Restriction of the EOS-guided steroid dosing protocol to periods of prolonged hospitalisation during the first 3 postoperative months should limit the requirement for higher prednisolone dosage without affecting immunosuppressive efficacy.

Error rates with which endomyocardial biopsy specimens are graded for rejection after cardiac transplantation.

Control of the immune response to the transplanted organ is fundamental to the success of transplantation. Endomyocardial biopsy to diagnose and grade rejection is the mainstay in achieving this control. As rejection tends to be a patchy process, accurate diagnosis depends on adequate sampling from the myocardium. This study estimates the error rates with which biopsy specimens are graded. The results of 459 biopsy sets, in which at least 4 fragments were graded, were analyzed. Combinations of grades observed at the same biopsy session were used to estimate error rates. An E-M algorithm was used to estimate error rates. Predictive probabilities of true grades, given a set of 4 graded fragments, were calculated using Bayes theorem. If 4 fragments at a biopsy session were negative there was a 0.02% chance of missing clinically significant rejection (moderate or severe). Similarly, if minimal rejection was the highest grade observed, the probability of missing moderate-severe rejection was negligible, between 0.06 and 0.09%. However, where mild rejection is the highest observed on the 4 fragments, there is between a 2% (1 mild fragment) and 28% (4 mild fragments) chance of moderate-severe rejection being the underlying grade. This study concludes that 4 fragments are adequate as a minimum in most cases. However, if only 4 fragments are available, and greater than or equal to 3 are graded mild, the risk of missing moderate-severe rejection is unacceptably high, and repeat biopsy or treatment may be indicated.

Effects of the immunosuppressant cyclosporine on the circulation of heart transplant recipients.

The effect of cyclosporine on the systemic circulation and on heart rate is unknown for heart transplant recipients. Thirty-four heart transplant recipients were studied by right-sided cardiac catheterization after endomyocardial biopsy. A direct linear relation was found between systemic and pulmonary vascular resistance and cyclosporine trough blood levels, which were negatively related to heart rate. The effect of cyclosporine on pulmonary vascular resistance, however, was not statistically significant by multivariate analysis when patient age was considered. In contrast, renal function appeared unrelated to systemic vascular resistance or heart rate. It appears that cyclosporine trough blood levels may have a direct effect on systemic vascular resistance as well as an unexplained negative chronotropic effect on heart rate.

The heart failure revascularisation trial (HEART): rationale, design and methodology.

BACKGROUND: Most patients with heart failure due to left ventricular systolic dysfunction (LVSD) secondary to coronary artery disease (CAD) have evidence of myocardium in jeopardy (reversible ischaemia and/or stunning hibernation). It is not known whether revascularisation in such cases is safe or beneficial. AIMS: To determine whether revascularisation will improve the survival of patients with LVSD and heart failure secondary to CAD and myocardium in jeopardy. METHODS: This is a randomised controlled trial comparing revascularisation or not, in addition to optimal medical therapy with ACE inhibitors, beta-blockers, aldosterone antagonists and an anti-thrombotic agent. Patients must have heart failure requiring treatment with diuretics, a left ventricular ejection fraction <35% and evidence of coronary disease. Myocardial viability and ischaemia are assessed by a broad range of techniques including stress echocardiography and nuclear imaging. All imaging tests are reviewed in core laboratories to ensure uniform reporting. Any conventional revascularisation technique is permitted. The primary outcome measure is all cause mortality. Symptoms, quality of life and health economic issues will also be explored. Assuming an annual mortality of 10% in the control group and allowing for substantial cross-over rates, a study of 800 patients followed for 5 years has 80% power with an alpha of 0.05 (two-sided) to show a 25% reduction in mortality with revascularisation. RESULTS: At the time of writing 180 patients have been screened for inclusion, 111 have consented to participate and 70 have been randomised. The results of viability testing are awaited in 22 patients. Twenty-six patients had been investigated for myocardial viability and/or by angiography prior to consent, as part of the routine practice in that cardiology department. Of 68 patients who have completed assessment only after consent, 47 (69%) were included. The principal reason for drop-out between consent and randomisation was lack of evidence of myocardial ischaemia or hibernation. CONCLUSION: The HEART trial will help to determine whether investigation of myocardial ischaemia and/or viability with a view to revascularisation should become part of the routine care of patients with heart failure due to LVSD and CAD.

Domino heart transplantation: the Papworth experience.

The use of donor hearts from heart-lung recipients, the so-called domino procedure, began at Papworth Hospital in November 1988. Between then and September 1992, 198 heart transplantations and 86 heart-lung transplantations were performed. Fifty-three heart-lung recipients donated their hearts for use in the domino procedure. Thirty-two domino hearts were transplanted at Papworth and 21 were exported to other centers. Institution of the domino procedure allowed us to perform 19% more heart transplantations (166 to 198) than would have been done had the procedure not been used. The ischemic time was significantly shorter for the domino hearts compared with organs from brain dead donors (134 minutes versus 191 minutes; p < 0.001). No difference was found in the 3-month (84% versus 83%) or 1-year (74% versus 76%) survival between domino and nondomino recipients. Other potential advantages of the domino procedure include detailed pretransplantation evaluation of the heart in live donors and the potential for human leukocyte antigen matching. Additionally many heart-lung recipients have elevated pulmonary artery pressures and a "conditioned", hypertrophied right ventricle. The use of such hearts for heart transplantation has theoretic appeal for patients with elevated pulmonary vascular resistance.

Transforming the "unacceptable" donor: outcomes from the adoption of a standardized donor management technique.

BACKGROUND: Donor management remains one of the most neglected areas of transplantation. A comprehensive donor management regimen has been developed. The results of the application of this strategy form the basis of this report. METHODS: Full hemodynamic data were collected from 150 multiorgan donors between October 1990 and August 1993. The data were collected at the time of donor team arrival, after insertion of a pulmonary artery floatation catheter and immediately before cardiac excision. RESULTS: Fifty-two donors (35%) fell well outside our minimum acceptance criteria on arrival. Twenty-one of fifty-two had a mean arterial pressure less than 55 mm Hg (mean 47 mm Hg) despite inotropic support in most cases; 10 of 52 had a central venous pressure greater than 15 mm Hg (mean 18.0 mm Hg); 2 of 52 had a high inotrope requirement greater than 20 micrograms/kg/min (mean 25 micrograms/kg/min). After the insertion of a pulmonary artery floatation catheter, an additional 13 of 52 donors were found to have a pulmonary capillary wedge pressure greater than 15 mm Hg (mean 19.8 mm Hg), and the final 6 of 52 had a low left ventricular stroke work index, less than 15 gm (mean 12.8 gm). After optimal management, including hormone replacement 44 of 52 donors yielded transplantable organs (29 hearts, 15 heart and lung blocks). Thirty-seven of forty-four patients (84%) were alive and well from 13 to 48 months after transplantation. There were five early deaths (11%) caused by infection (heart), adult respiratory distress syndrome (heart), arrhythmia (heart), cerebrovascular event (heart and lung), and infection (heart, lung, and liver). Two late deaths (5%) occurred as a result of tamponade (3 months, heart) and infection (14 months, heart and lung). Eight of fifty-two organs were still unsuitable for transplantation after optimum management during the splanchnic dissection as a result of inotrope dependency (n = 4), left ventricular hypertrophy (n = 2), and coronary artery disease (n = 2). CONCLUSIONS: The data indicate that, of the organs which initially fall outside our transplant acceptance criteria, 92% are capable of functional resuscitation. Conversely, superficial assessment may not show compromised function. Optimizing cardiovascular performance also has important implications for the viability of all transplantable organs. This aggressive approach to donor management has resulted in the transplantation of 44 donor hearts that may otherwise have been turned down or inappropriately managed.