H.L. Thomas

UK guidelines for referral and assessment of adults for heart transplantation

Patients with advanced heart failure have a dismal prognosis and poor quality of life. Heart transplantation provides an effective treatment for a subset of these patients. This article provides cardiologists with up-to-date information about referral for transplantation, the role of left ventricular assist devices prior to transplant, patient selection, waiting-list management and donor heart availability. Timing is of central importance; patients should be referred before complications (eg, cardiorenal syndrome or secondary pulmonary hypertension) have developed that will increase the risk of, or potentially contraindicate, transplantation. Issues related to heart failure aetiology, comorbidity and adherence to medical treatment are reviewed. Finally, the positive role that cardiologists can play in promoting and facilitating organ donation is discussed.

Effect of donor smoking on survival after lung transplantation: a cohort study of a prospective registry

BACKGROUND The risk that a positive smoking history in lung donors could adversely affect survival of transplant recipients causes concern. Conversely, reduction of the donor pool by exclusion of donors with positive smoking histories could compromise survival of patients waiting to receive a transplant. We examined the consequences of donor smoking on post-transplantation survival, and the potential effect of not transplanting lungs from such donors. METHODS We analysed the effect of donor smoking on 3 year survival after first adult lung transplantation from brain-dead donors done between July 1, 1999, and Dec 31, 2010, by Cox regression modelling of data from the UK Transplant Registry. We estimated the effect of acceptance of lungs from donors with positive smoking histories on survival and compared it with the effect of remaining on the waiting list for a potential transplant from a donor with a negative smoking history donor, by analysing all waiting-list registrations during the same period with a risk-adjusted sequentially stratified Cox regression model. FINDINGS Of 1295 lung transplantations, 510 (39%) used lungs from donors with positive smoking histories. Recipients of such lungs had worse 3 year survival after transplantation than did those who received lungs from donors with negative smoking histories (unadjusted hazard ratio [HR] 1·46, 95% CI 1·20-1·78; adjusted HR 1·36, 1·11-1·67). Independent factors affecting survival were recipients age, donor-recipient cytomegalovirus matching, donor-recipient height difference, donors sex, and total ischaemic time. Of 2181 patients registered on the waiting list, 802 (37%) died or were removed from the list without receiving a transplant. Patients receiving lungs from donors with positive smoking histories had a lower unadjusted hazard of death after registration than did those who remained on the waiting list (0·79, 95% CI 0·70-0·91). Patients with septic or fibrotic lung disease registered in 1999-2003 had risk-adjusted hazards of 0·60 (95% CI 0·42-0·87) and 0·39 (0·28-0·55), respectively. INTERPRETATION In the UK, an organ selection policy that uses lungs from donors with positive smoking histories improves overall survival of patients registered for lung transplantation, and should be continued. Although lungs from such donors are associated with worse outcomes, the individual probability of survival is greater if they are accepted than if they are declined and the patient chooses to wait for a potential transplant from a donor with a negative smoking history. This situation should be fully explained to and discussed with patients who are accepted for lung transplantation. FUNDING National Health Service Blood and Transplant.

The importance of cold and warm cardiac ischemia for survival after heart transplantation

Background. Ischemia time is a risk factor for mortality after heart transplantation that can be influenced by organizational factors such as transport arrangements and organ allocation. Methods. We used the United Kingdom Cardiothoracic Transplant Audit database to analyze the outcome of 1491 first isolated orthotopic adult heart transplants performed between April 1995 and March 2004. Ischemia time and its components (transport time and surgical implant time) were related to 30-day mortality using a multivariable logistic regression model. Results. The median total ischemia time increased from 171 min (interquartile range: 149–198) to 213 min (interquartile range: 181–256) during the study period (P<0.0001). This was due to an increase in transport times that was partly explained by increased organ exchange between centers and also because of an increase in surgical implant times. Thirty-day survival decreased over the study period (91%–84%) with some evidence of a linear trend towards decreasing survival over time (P=0.089). After correcting for other known risk factors, the odds ratio of death within 30 days associated with each 15 min increment in transport time was 1.06 (95% confidence interval: 1.01–1.12) and with each 15 min increment in surgical implant time was 1.11 (95% confidence interval: 1.04–1.18). Conclusion. Both transport and implant times were directly related to 30-day mortality after heart transplantation. Ischemia time should be considered in organ allocation and controlled during the heart transplant procedure.

Incidence, determinants and outcome of chronic kidney disease after adult heart transplantation in the United Kingdom

Background We investigated the incidence of chronic kidney disease (CKD) in the United Kingdom heart transplant population, identified risk factors for the development of CKD, and assessed the impact of CKD on subsequent survival. Methods Data from the UK Cardiothoracic Transplant Audit and UK Renal Registry were linked for 1732 adult heart transplantations, 1996 to 2007. Factors influencing time to CKD, defined as National Kidney Foundation CKD stage 4 or 5 or preemptive kidney transplantation, were identified using a Cox proportional hazards model. The effects of distinct CKD stages on survival were evaluated using time-dependent covariates. Results A total of 3% of patients had CKD at transplantation, 11% at 1-year and more than 15% at 6 years posttransplantation and beyond. Earlier transplantations, shorter ischemia times, female, older, hepatitis C virus positive, and diabetic recipients were at increased risk of developing CKD, along with those with impaired renal function pretransplantation or early posttransplantation. Significant differences between transplantation centers were also observed. The risk of death was significantly higher for patients at CKD stage 4, stage 5 (excluding dialysis), or on dialysis, compared with equivalent patients surviving to the same time point with CKD stage 3 or lower (hazard ratios of 1.66, 8.54, and 4.07, respectively). Conclusions CKD is a common complication of heart transplantation in the UK, and several risk factors identified in other studies are also relevant in this population. By linking national heart transplantation and renal data, we have determined the impact of CKD stage and dialysis treatment on subsequent survival in heart transplant recipients.

Trends in adult heart transplantation: a national survey from the United Kingdom Cardiothoracic Transplant Audit 1995–2007,

OBJECTIVE The management of heart failure (HF), peri-transplant care and immunosuppression has changed in the last decade. Here we describe the changes that have occurred in the UK national programme of adult heart transplantation (HTx). METHODS Using the data accrued with the UK Cardiothoracic Transplant Audit we undertook a prospective cohort study of 2958 consecutive adult patients listed for HTx and 2005 adult orthotopic HTx performed in three time periods - Era-1 (July 1995-March 1999, 1321 listed, 907 transplanted), Era-2 (April 1999-March 2003, 842 listed, 600 transplanted) and Era-3 (April 2003-March 2007, 795 listed, 498 transplanted). RESULTS The median time on the waiting list reduced from 109 days in Era-1 to 40 days in Era-3. The proportion of HTx in non-ambulatory HF patients requiring inotropic or circulatory support increased from 12% in Era-1 to 35% in Era-3. The proportion undergoing HTx for non-ischaemic dilated cardiomyopathy increased from 40% in Era-1 to 58% in Era-3 while ischaemic cardiomyopathy decreased. Survival after HTx remained constant (81% (95% CI: 78-83%) at 1 year in Era-1 and 80% (95% CI: 77-84%) in Era-3). There was an increase in the use of mycophenolate and induction therapy and a reduction in rejection episodes over the eras. CONCLUSIONS Although waiting list and HTx activity have declined, HTx continues to have an important role in the management of advanced HF, especially for patients on inotropic or circulatory support. Despite a deterioration of donor organ quality, survival after HTx has remained unchanged.