Heart-lung transplantation.
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Cyclosporins↗
Biomedical subjects
J Wallwork
Publications and source records attributed to J Wallwork.
The haemodynamic effects of sodium nitroprusside following cardiopulmonary bypass: a clinical study.
Measurements of cardiac index were made in 18 patients (14 male and 4 female) preoperatively and thereafter during a 12-hour period immediately following coronary artery bypass grafting for stable angina pectoris. Patients with evidence of impaired left ventricular function were not included in the study. Individuals were allocated randomly to one of two groups. The first group received sodium nitroprusside as a constant, variable dose infusion during the post bypass study period (nitroprusside group). The second group received no nitroprusside (control group). The operative and postoperative management of these patients was otherwise identical. Following bypass, both groups showed a gradual drop in cardiac index with an associated increase in peripheral vascular resistance. In the control group, the mean cardiac index fell below the mean preoperative value. In the nitroprusside group, however, the mean cardiac index always remained above the mean preoperative level for the group, the differences between the groups being statistically highly significant at 1 1/2 hours postoperatively (p less than .005) and still significant at 3 hours postoperatively (p less than .05). The subsequent rise in cardiac index over the next 9 hours was more rapid in the nitroprusside treated patients and left ventricular function was better as demonstrated by a consistently higher mean cardiac index for any given left ventricular filling pressure. It is concluded that nitroprusside increases cardiac output and improves left ventricular function in the early postoperative period following cardiopulmonary bypass.
Blood Pressure↗
Epstein-Barr virus infection in heart and heart-lung transplant recipients: incidence and clinical impact.
BACKGROUND: A retrospective serologic study was made of 67 heart-lung and 295 heart transplant recipients (with transplantations at Papworth Hospital, Cambridge, England) to determine the incidence and clinical impact of Epstein-Barr virus infection. METHODS: Epstein-Barr virus capsid antigen immunofluorescence tests were performed, and the antibody avidity was determined by modifying the washing procedure to include a mild reducing agent (8M urea). RESULTS: This testing showed that 6.0% of the patients had primary Epstein-Barr virus infections, whereas 17.4% had the reactivation of a past infection. Primary infections were only detected in patients who were Epstein-Barr virus antibody-negative before transplantation, who had received an organ from an Epstein-Barr virus antibody-positive donor. Of the patients with serologically proven Epstein-Barr virus infections, 52.9% had symptoms. Although these were generally mild, five heart and two heart-lung transplant recipients had malignant lymphoma and one heart and one heart-lung transplant recipient had lymphoproliferative disease after Epstein-Barr virus infection. Additional four heart transplant recipients had lymphoma after transplantation. None of these four patients had evidence of active Epstein-Barr virus infection; one was Epstein-Barr virus antibody-negative during the study period and three had stable Epstein-Barr virus virus capsid antigen immunoglobulin G titers throughout. CONCLUSIONS: Epstein-Barr virus infection in organ transplant recipients may lead on to life-threatening lymphoproliferative disease or lymphoma. For this reason it may be beneficial to monitor patients after transplantation for evidence of Epstein-Barr virus infection and to follow the progress of those affected.
Adolescent↗
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.
Adult↗
Ethical considerations in clinical cardiac xenografting.
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Animals↗
Functional assessment and management of heart donors: a rationale for characterization and a guide to therapy.
BACKGROUND: Traditional methods for the functional evaluation of a donor heart have relied on superficial hemodynamic data and visual inspection of the action of the heart at sternotomy. The International Registry has continued to report significant mortality for heart transplant recipients from primary graft dysfunction that may be due to donor management, donor organ selection, organ preservation, or recipient factors. The literature reports the loss of at least 25% of potential donors because of the provision of inadequate physiologic support. METHODS AND RESULTS: We have now spent several years in establishing and refining a strategy for optimizing donor management, which has resulted in the safe expansion of our donor pool by approximately 30%. Central to this management regimen has been the use of comprehensive perioperative invasive monitoring used by a cardiac anesthetist who takes responsibility for donor management during the retrieval operation. CONCLUSION: This article outlines the technique which has evolved for the functional evaluation of a donor heart, which is now used in our institution as a guide to management and as a basis for decision making regarding organ suitability.
Adolescent↗
Heart transplantation in the United Kingdom: who waits longest and why.
BACKGROUND: This study aims to identify characteristics that increase the chance of death of potential cardiac transplant recipients before donor organs become available. METHODS: Between June 1, 1988, and May 31, 1993, 332 patients were accepted for heart transplantation; 235 underwent surgery. Ninety-seven patients had not received transplants; of these, 71 died, 13 were transferred to other lists, and 13 were awaiting organs at the close of the study. Median waiting time for those patients who received organs was 109 days, whereas patients who did not receive organs spent a median of 94 days on the list. Recipients are matched to donor organs according to blood group, size (height), and, recently, preoperative transpulmonary pressure gradient. Recently cytomegalovirus antibody mismatches (positive donor to negative recipient) have been avoided where possible. These factors, together with age, gender, underlying diagnosis, previous heart surgery, and Toxoplasma antibody status were studied to assess their influence on waiting time and survival. RESULTS: No characteristics were found significantly to influence survival after acceptance, so that the chance of death while the patient was waiting for heart transplantation is mainly affected by the severity of disease and the length of time a patient waits. In multivariate analyses the following were independently significantly associated with shorter waiting times: small patients (< 1.7 m tall; p = 0.005), patients with blood types B and AB (p = 0.003), and patients with cardiomyopathy (p < 0.001). CONCLUSIONS: These results can be used by cardiologists to help assess the time at which a patient should be referred for transplantation.
Blood Grouping and Crossmatching↗
Airway stenoses after lung transplantation: management with expanding metal stents.
Success in lung transplantation has been hindered by airway complications, usually as a result of anastomotic ischemia and stenosis. We report our experience with expanding metal stents in managing airway stenoses after lung transplantation. From April 1984 through November 1993, 46 single lung, 5 double lung, and 154 heart-lung transplantations were performed at Papworth Hospital. All patients received immunosuppression with azathioprine, cyclosporine, methylprednisolone, and induction antithymocyte globulin. Fourteen patients (nine single lung, two double lung, and three heart-lung) had an airway stenosis requiring a stent. The most common features were shortness of breath, wheezing or stridor, and a fall in pulmonary function tests (11 patients). Three patients had pneumonia. Airway stenosis was diagnosed on bronchoscopy an average of 61 days after transplantation (range 3 to 245 days). Stent placement occurred an average of 18 days after the diagnosis (range 2 to 84 days). One heart-lung transplant recipient received a silicone rubber stent. All other patients received expanding metal stents. Six patients required multiple stent placements. After stent placement the average increase in the forced expiratory volume in 1 second was 117%. Infection complicated the stenoses in 12 patients. Pseudomonas aeruginosa and Aspergillus fumigatus were the most common pathogens, each occurring in six cases. Multiple pathogens were isolated in seven cases. Three patients died as a direct consequence of their airway problems. Two died of pneumonia despite stenting, and a third died of acute occlusion of the silicone rubber stent. Expanding metal stents are an effective treatment of airway stenoses in lung transplant recipients. Patients with suspected airway problems should be referred for early bronchoscopy with the potential for stent placement.
Adult↗
Who waits longest for heart and lung transplantation?
Between August 1982 and December 1992, 260 patients were accepted for heart and lung transplantation, of whom 139 patients underwent transplant surgery. One hundred twenty-one patients have not received transplants, of whom 80 have died, four were transferred to other lists, and 37 were still waiting for suitable organs at the close of the study. Median waiting time for those patients who underwent heart and lung transplantation was 7 months, whereas patients who died waiting spent a median of 5 months on the list. Recipients are matched to donor organs according to blood type, size (total lung capacity), and cytomegalovirus antibody status. These factors, along with age, gender, underlying diagnosis, and Toxoplasma antibody status, were studied to assess their influence on survival after acceptance and time to transplantation. The only characteristic that significantly influenced survival after acceptance was the underlying disease, with patients with Eisenmenger's syndrome having significantly longer survival than the other groups (relative risk = 0.21; p < 0.001). Patients with Eisenmenger's syndrome underwent transplantation at a slower rate than did other patients (relative risk = 0.51; p = 0.012). Patients who had a total lung capacity of more than 6 L underwent transplantation significantly more quickly than did smaller patients (relative risk = 1.98; p = 0.005). Male patients underwent heart and lung transplantation at a quicker rate than did female patients (relative risk = 1.86; p < 0.001), although this was related to size. Patients who had cytomegalovirus-positive antibodies underwent transplantation at almost twice the rate of patients who had cytomegalovirus-negative antibodies (relative risk = 1.92; p < 0.001). Age at acceptance, blood type, and Toxoplasma status did not significantly influence time to heart and lung transplantation. In summary, cytomegalovirus antibody status, patient size, and gender significantly affect the waiting time to heart and lung transplantation. Patients with Eisenmenger's syndrome wait longer than other patients as a result of the natural history of their disease.
Adolescent↗
Expanding the donor pool: pushing to the limit.
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Heart Function Tests↗
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.
Actuarial Analysis↗
Harvesting of domino hearts.
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Anastomosis, Surgical↗
Heart-lung transplantation for end-stage respiratory disease in patients with cystic fibrosis at Papworth Hospital.
Between October 1985 and July 1992 we performed heart-lung transplantation in 42 patients with end-stage respiratory disease caused by cystic fibrosis. Twenty-eight of these patients are alive at 3 months to 7 years after heart-lung transplantation. Actuarial survival at 1 year and 3 years after transplantation was 78% and 65%, respectively, in this group, which compares favorably with 77% and 60%, respectively, in patients without cystic fibrosis undergoing heart-lung transplantation. Similarly no significant difference was found in the incidence of postoperative infections between patients with cystic fibrosis and patients without cystic fibrosis undergoing heart-lung transplantation. Quality of life indexes analyzed by the Nottingham Health Profile reveal significant improvements for patients surviving longer than 3 months from surgery. Long-term survival is determined by the development of obliterative bronchiolitis, which has occurred in 11 patients, six of whom have died. Early postoperative survival appears to be compromised by poor preoperative nutritional status. The study provides evidence that patients with end-stage respiratory disease caused by cystic fibrosis gain a survival advantage and improvement in quality of life after heart-lung transplantation when compared with patients who do not receive this form of therapy.
Actuarial Analysis↗
Incidence of obliterative bronchiolitis after heart-lung transplantation in children.
Between June 1988 and February 1993, combined heart-lung transplantation was performed in 30 children and adolescents aged 3.6 to 18.6 years (mean, 12.2 years) at The Hospital for Sick Children in London. Original diagnoses included cystic fibrosis (n = 25), Eisenmenger's syndrome (n = 4), and chronic graft-versus-host disease of the lung (n = 1). Posttransplantation maintenance immunosuppression comprised a triple regimen, with methylprednisolone and antithymocyte globulin given perioperatively and for episodes of allograft rejection. Actuarial survival was 63% (95% confidence interval: 42%-78%) at 1 year and 48% (95% confidence interval: 27%-66%) at 3 years. Obliterative bronchiolitis has been diagnosed in 13 patients (43%). Actuarial freedom from obliterative bronchiolitis in survivors was 76%, 59%, and 37% at 12, 24, and 36 months after transplantation, respectively. Recipients in whom obliterative bronchiolitis developed within the first year (n = 6) had more episodes of pulmonary rejection during the first 6 months after transplantation (mean, 5.7 episodes per patient) than those in whom "premature" obliterative bronchiolitis did not develop (mean, 3.2 episodes per patient). Infection of the pulmonary allograft was implicated to a lesser extent in predisposing to obliterative bronchiolitis. At 2, 3, and 6 months, tracheal stenosis developed in three patients, all of whom died with obliterative bronchiolitis within 10 months of transplantation. Noncompliance with therapy was considered a contributory factor in producing obliterative bronchiolitis in four adolescent recipients. The high incidence of obliterative bronchiolitis observed in this pediatric cohort may have a multifactorial cause.
Actuarial Analysis↗
A method of analyzing the onset and progression of coronary occlusive disease after transplantation and its effect on patient survival.
The development of transplant-acquired coronary occlusive disease is monitored with serial angiography and is graded on a three-point scale as normal, mild (< 50% stenosis), or severe (> or = 50% stenosis). Previous studies have provided information about the time to the first sign of disease on angiography or empirical descriptions of progression. The number of observed transitions between grades of disease has been recorded, and a Markov model based on these transitions is used to estimate the rate of progression through angiographically defined disease grades and the mortality rates from each grade. Five hundred thirty-six angiograms from 240 patients were analyzed. Fifty-three graft failures occurred. The annual transition rate per patient year from normal to mild disease was low, 0.120 (95% credible interval, 0.096 to 0.154), although the transition from mild to severe disease was relatively high, 0.482 (95% credible interval, 0.325 to 0.671). Annual death rates from normal, mild, and severe grades were 0.032 (95% credible interval, 0.016 to 0.052), 0.076 (95% credible interval, 0.007 to 0.187) and 0.415 (95% credible interval, 0.244 to 0.640), respectively. Before onset of disease patients have a hazard-free course, and mild disease displayed on angiography is relatively non-life-threatening. However, once mild disease has been detected by angiography, progression to severe disease is rapid, and severe disease carries a very poor prognosis.
Adolescent↗
Cardiac surgery in older people--the Papworth experience.
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Age Factors↗
Prognosis of patients with cystic fibrosis awaiting heart and lung transplantation.
Heart-lung transplantation is a successful treatment for patients with cystic fibrosis and chronic respiratory failure. Patients are assessed for surgery when life expectancy is deemed short. This study assesses the ability of measurements of pulmonary function, blood gas levels, and nutritional status to predict survival of patients awaiting heart-lung transplantation and to assess the effect of heart-lung transplantation on survival. Sixty-seven patients with cystic fibrosis were accepted for heart-lung transplantation from 1985 through 1990. Each patient underwent tests of pulmonary function, exercise tolerance, blood-gas levels, and nutritional status. Cox regression was used to analyze the prognostic value of these data. Of the 67 patients accepted for heart-lung transplantation, organs became available for 30; 24 patients died waiting, and 13 patients were on the list December 31, 1990. Eight patients died after transplantation. Patients with above-average forced expiratory volume in 1 second (FEV1) (median, 17% predicted) at assessment were half as likely to die waiting (relative risk, 0.47; 95% confidence interval, 0.23 to 0.97) as patients with below-average FEV1. The relative risk of death for patients on the waiting list was 1.44 (95% confidence interval, 1.17 to 1.77) for each increment in PCO2 of 1 kPa. No effect of nutritional status on waiting list death was found, but seven of eight patients who died after heart-lung transplantation were below 80% predicted weight for height. Using a time-dependent analysis, heart-lung transplantation almost halved the risk of death (relative risk, 0.57; 95% confidence interval, 0.22 to 1.48). Postoperative actuarial survival was 79% (95% confidence interval, 63% to 95%).(ABSTRACT TRUNCATED AT 250 WORDS)
Carbon Dioxide↗
Lack of association between endomyocardial evidence of rejection in the first six months and the later development of transplant-related coronary artery disease.
The development of transplant-related coronary artery disease (TCAD) is the major determinant of long-term heart transplant survival. To test the hypothesis that TCAD might be related to cellular myocardial rejection, the grades of rejection seen at all biopsies performed in the first 6 months after heart transplantation were analyzed in 108 patients who survived more than 6 months. The development of TCAD was assessed at routine follow-up coronary angiography in 101 patients and at necropsy in seven patients. This data was analyzed with Kaplan-Meier survival curves and Cox proportional hazard regression analysis. No significant association was found between either moderate rejection or any level of rejection and the later development of TCAD, nor did the absence of any rejection protect against its development.
Biopsy, Needle↗