Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Heart Transplantation
- T J Locke (1 September 2000)
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Cardiac transplantation
- David Wainwright Evans (1 September 2000)
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Re: Heart Transplantation
- Mario C Deng (1 September 2000)
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Re: Cardiac transplantation
- Mario C Deng (3 September 2000)
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Comments on heart transplantation
- Herbert Nägele (13 September 2000)
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Criteria used to list patients for heart transplantation
- Guy A MacGowan (2 October 2000)
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Effect of receiving a heart transplant
- Linda Sharples (2 October 2000)
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Effect of receiving a heart transplant
- N R Banner (2 October 2000)
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T J Locke, Consultant Cardiothoracic Surgeon Northern General Hospital Sheffield
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Editor, Deng et al conclude that heart transplantation has little effect on the survival of patients with heart failure. This was based on a one-year survival of 71% after transplantation. This survival rate differs from the UK average one-year survival of 79% and differs from one-year survival rates in excess of 90%, reported by several units around the world, including Sheffield (Audit data from the Clinical Effectiveness Unit of the Royal College of Surgeons of England). A different view of the data offered by Deng et al is that heart transplantation should be offered by the best transplant units to the sickest patients. TJ Locke
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David Wainwright Evans, Retired cardiologist
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Human cardiac transplantation is fundamentally flawed. It requires the removal of a functional heart from someone who is not really dead but only notionally dead - in this country, "brain stem dead". That diagnosis properly applies to a pre-mortal syndrome. There were never sound scientific, logical or philosophical grounds for its equation with death. It is now clear that it is unethical even to make that diagnosis because the crucial apnoea test may exacerbate the cerebral damage (1). In light of the above, it should occasion no surprise that the efficacy of cardiac transplantation has been called into question (2,3). It flourished, for a while, because of its sensational appeal. But, as it did so, its hunger for scarce resources meant that many patients who could have benefited from cardiac surgery of proven efficacy were denied the chance of restoration to vigorous health. They and those who succumbed unnecessarily - for lack of the urgent, truly life-saving, surgery which they would have had but for transplantation - must figure somewhere in the overall profit-and-loss account of this misguided enterprise. As a colleague remarked many years ago, heart transplants have increased rather than decreased the sum of human misery. David W. Evans, Sometime Consultant Cardiologist at Papworth Hospital, 27 Gough Way, Cambridge, CB3 9LN 1. Coimbra CG. Implications of ischemic penumbra for the diagnosis of brain death. Braz J Med Biol Res 1999;32:1479-1487. 2. Deng MC et al. Effect of receiving a heart transplant: analysis of a national cohort entered on to a waiting list, stratified by heart failure severity. BMJ 2000;321:540-545. 3. Watanabe Y. Why do I stand against the movement for cardiac transplantation in Japan? Jpn Heart J 1994;35:701-714. |
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Mario C Deng, Director of Cardiac Transplantation Research Columbia University College of Physicians & Surgeons, New York
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Locke and colleagues have made an important point: The survival benefit of cardiac transplantation can be maximized not only by selecting patients at highest risk of dying from heart failure but also by optimizing outcomes after transplantation. This goal implies the creation of a national infrastructure with comprehensive regional heart failure/transplantation centers offering all aspects of heart failure care including medical treatment, high risk conventional surgery, mechanical circulatory support as well as transplantation. It requires a state-of-the -art interdisciplinary approach between cardiologists and cardiac surgeons as well as physician staff and nurses, psycholgists, and social workers at the center and a responsibility of the center for the region. It also requires a reliable auditing mechanism. This is a health policy issue of high priority. Mario C Deng |
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Mario C Deng, Director of Cardiac Transplantation Research Columbia University College of Physicians & Surgeons
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To Dr. Evans: Our paper seems to have stimulated a discussion which is beyond the scope of the presented data and aims at the theoretical foundations of cardiac transplantation. A comprehensive review – beyond the scope of this letter - would require a focus on different constitutive components of the cardiac transplantation process including the history of the heart replacement paradigm in medicine, the brain death concept, principles guiding recipient and donor selection, allocation criteria, organizational structures, quality control mechanisms, alternative treatment research, teaching, and societal policy making. The German transplantation law of 1997 which was passed after an extensive public debate embraces the concept of brain death. The brain death concept originated from advances in intensive care medicine before the era of transplantation which rendered patient care undetermined with regard to ethical categories in borderline critical care situations and required a new operational definition of death in order to propagate a humane high technology medicine. Our data question the efficacy of contemporary cardiac transplantation in Germany not because of ethical considerations related to the brain death definition but because of inadequate recipient selection criteria. The unproportionately high public attention which cardiac transplantation has received in the past can not be entirely attributed to its impact on public health. One may speculate with Dr Evans that nonmedical factors have contributed to this phenomenon. Based on our study results it may be predicted that the role of cardiac transplantation will evolve from being the isolated gold standard in the therapy of severe heart failure to becoming part of a family of equally important medical and surgical treatment options. This development will reduce its “sensational appeal” and at the same time enhance the beneficial effects on survival and quality of life which each of these therapies will have if they are carefully tailored by us to our individual patients’ needs. |
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Herbert Nägele, Transplant Cardiologist University Hospital Hamburg-Eppendorf, Germany
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Dear Editor - We want to add some comments to the interesting paper of DENG et al. (1) and to the corresponding editorial of Sharon Hunt (2) published in the september 2nd edition of the BMJ. The major finding in the report is that only high risk patients as stratified with a heart failure survival score are likely to profit from heart transplantation (HTx) in terms of survival. A high risk was found in only 107 of 889 patients (12%) listed for HTx in Germany in 1997. Does this mean that about 90% of patients in Germany were placed on the HTx waiting list without a clear-cut indication? This question highlights the need for independent auditing to improve the efficacy of this procedure with respect to the very limited ressources. In our means auditing should rely not only on organ distribution but should focus primarily on an optimal medical therapy at time of listing because in contrast to surgical procedures pharmacotherapy of heart failure is vigourosly tested in randomized studies (eg. ACE inhibitors, ß-blockers, spironolactone etc.). We are in doubt whether a state of the art medical therapy is established in all heart failure patients which finally underwent transplantation. Indeed a mean heart rate of 85 beats/min and a mean arterial pressure of 82mmHg in the COCPIT trial suggests that beta-blocker therapy was not given and ACE inhibitor dosage was not maximized in many patients (1, table). That the introduction of ß-blockade is save even in NYHA IV patients has recently been shown in the COPERNICUS trail which was terminated by the DSMB due to a greatly reduced mortality in the carvedilol arm (3). Therefore no patient should be listed for heart transplantation before of at least one attempt of beta blockade has been undertaken. Individualized titration of medical therapy in HTx candidates is effective in improving survival on the waiting list. By this means rare donor hearts would be saved for those patients most needing a transplant (4). Such an approach reduces waiting times greatly and limits the exposure to many month of living under high risk (5). Further research should focus on the problem of sudden death in stabilized HTx candidates, which could be removed from the waiting list (6). This problem may be solved either pharmacologically with additional amiodarone (7) or with implantable cardioverter defibrillators. In their editorial HUNT stated that as a consequence of the paper of DENG et al. other alternatives to transplantation should be searched for such as mechanical circulatory support devices (2). In the above mentioned context these devices should be also termed as a pure experimental surgical method for which efficacy was not tested in controlled randomized trials. By restricting definite HTx listing to real high risk patients, transplantation could be performed in a shorter period of time completely abolishing the need for device implantation. Herbert Nägele, Wilfried Rödiger Dpt. of Cardiovascular Surgery, University Hospital Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany References 1) Deng MC, De Meester JMC, Smits JMA, Heinecke J, Scheld HH on behalf of the Comparative Outcome and Clinical Profils in Transplantation (COCPIT) Study Group. Effect of receiving a heart transplant: analysis of a national cohort entered on to a waiting list, stratified by heart failure severity. BMJ 2000; 321:540-5. 2) Hunt S. A fair way of donating hearts for transplantation. Survival rates improve only in patients with the worst heart failure. BMJ 2000; 321: 526 3) Communicated during the European Society of Cardiology Meeting Amsterdam, August 2000 4) Nägele H, Döring V, Kalmar P, Stubbe HM, Rödiger W. Intensified medical therapy in heart transplant candidates. Asia Pacific Heart Journal 1997; 6(3): 178-183. 5) Nägele H, Dapper F, Rödiger W. Intensified medical therapy and regional donor allocation in the management of patients with end stage heart failure. Z Kardiol 1998; 87: 676-682 6) Nägele H, Rödiger W. Sudden death and tailored medical therapy in candidates for heart transplantation. J Heart Lung Transplant 1999; 18: 869-876 7) Nägele H, Bohlmann M, Eck U, Petersen B, Rödiger W. Combination therapy with carvedilol and amiodarone in patients with severe heart failure. Eur J Heart F 2000; 2: 71-79 |
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Guy A MacGowan, Assistant Professor of Medicine, Cardiovascular Institute, University of Pittsburgh University of Pittsburgh Medical Center
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Dear Editor, We read with interest the article by Deng et al (1) regarding mortality benefit from heart transplant. We entirely agree with the overall conclusions of the paper, that only patients with a predicted high mortality should be listed for transplantation. However, we feel it is important to look closely at the patient characteristics, particular with regards to the peak exercise oxygen consumption data. Peak exercise oxygen consumption is recognized as an important predictor of outcome in heart failure patients (2) and has stood the test of time (3). Indeed, it is an important factor in the HFSS statistical model (4) as used in the present paper (1). Mancini et al (2) have shown that in patients with a peak exercise oxygen consumption less than 14 ml/kg/min that there was a significantly higher mortality compared to patients with a peak exercise oxygen consumption greater than 14 ml/kg/min. However, in the present study (1), in the COCPIT cohort mean peak exercise oxygen consumption is significantly higher than the Mancini criteria at 15.8 ml/kg/min. In addition this data was available in only 139 of the 889 patients. This leads to several questions. Firstly, it appears that this group of patients is relatively ‘well’ and so would not be predicted to have a high mortality, and therefore perhaps many of these patients should not have been listed for transplant. Secondly it must be questioned as to why this important predictor of outcome is only presented for 16% of the patients? The accurate assessment of patients for heart transplant is a critical issue to derive mortality benefit from this procedure. Failure to use accepted and meaningful tests such as peak exercise oxygen consumption may result in inappropriate listing of heart failure patients for transplantation. Yours sincerely, Guy A. MacGowan, MD FACC,
Srinivas Murali, MD FACC,
No competing interests. References: 1. Deng MC, De Meester JMJ, Smits JMA, Heinecke J, Scheld HH. Effect of receiving a heart transplant: analysis of a national cohort entered on to a waiting list, stratified by heart failure severity. BMJ 2000;321:540-545 2. Mancini DM, Eisen H, Kussmaul W, Mull R, Edmunds LH, Wilson JR. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation 1991;83:778-786 3. Mancini D, LeJemtel T, Aaronson K. Peak VO2. A simple yet enduring standard. Circulation 2000;101:1080-1082 4. Aaronson K, Schwartz JS, Chen T, Mancini D. Development and prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation. Circulation. 1997;95:2660-2667 |
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Linda Sharples
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Dear Editor - Rigorous evaluation of surgical procedures is important. The COCPIT study (1) called for an RCT of heart transplantation based on comparing post-operative and waiting list survival in a single year in Germany. However, the German registry's 12 month post-operative survival rate of 71% was significantly lower that either Papworth patients transplanted since 1990 (83%), or that published by the ISHLT (82% for patients transplanted since 1995) (2). This questions the generalisability of the results beyond Germany. Moreover, 12 month follow up is inadequate, as post-transplant risks are greatest in the first year, falling thereafter. The risks from end-stage heart failure are cumulative. COCPIT claims that there are patients listed for transplantation who are not 'sick' enough to derive survival benefit from the procedure. They agree that high risk patients derive survival benefit. The difficulty lies in identification of the group for which equipoise exists, at least in terms of survival. With increasing waiting lists and higher proportions of patients undergoing transplantation in UNOS status I, the demand of the high risk group may largely exhaust the supply of donated organs. This would leave few organs for the marginal candidates, for which randomisation may be appropriate. VO2max is an important prognosticator in the HFSS study and is widely adopted by transplant centres for this purpose (3). However, it was only available for 16% of those studied in COCPIT and substituting the mean for missing values is questionable. This casts doubt on the HFSS, which is unvalidated in the era of b blocker therapy or as a prognosticator in transplantation (4). Over the last 10 years compelling evidence has emerged that heart transplantation confers large and significant improvements in health related quality of life. Although there have been no randomised studies, within patient changes pre- to post-transplantation are unequivocal. For example, in 1990, using the Nottingham Health Profile, we showed large, significant improvements in all physical and psychological dimensions (5), with improvements maintained to 5 years in survivors. During the 1990s the evidence of improved quality of life from elsewhere has been steadily mounting. COCPIT has raised the importance of careful selection of transplant candidates, which should be done in large experienced centres. With mounting evidence of improved post-op survival and clinically important, significant improvements in health related quality of life, we are surely too late for an RCT. Authors: DK Satchithananda, LD Sharples, SC Stoica, J Parameshwar, SR Large, J Wallwork. References: 1. Deng MC, De Meester MJ, Smits JMA, Heinecke J, Scheld HH on behalf of the Comparative Outcome and Clinical Profiles in Transplantation (COCPIT) Study Group. Effect Of Receiving A Heart Transplant: Analysis Of A National Cohort Entered On To A Waiting List, Stratified By Heart Failure Severity. BMJ 2000; 321: 540-545. 2. Hosenpud JD, Bennett LE, Keck BM, Fiol B, Boucek MM, Novick RJ. The Registry Of The International Society Of Heart And Lung Transplantation: Sixteenth Official Report-1999. J Heart & Lung Transplant. 1999;18:611-626. 3. Mancini D, LeJemttel T, Aaronson K. Peak VO2: A Simple Yet Enduring Standard. Circulation. 2000; 101: 1080-1082. 4. Aaronson KD, Schwartz JS, Chen TM, Wong KL, Goin JE, Mancini DM. Development And Prospective Validation Of A Clinical Index To Predict Survival In Ambulatory Patients Referred For Cardiac Transplant Evaluation. Circulation. 1997; 95: 2660-2667. 5. Caine N, Sharples LD, English TAH, Wallwork J. Prospective Study Comparing Quality Of Life Before And After Heart Transplantation. Transplant Proceed. 1990; 22: 1437-1439. |
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N R Banner
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Sir - The article by Mario Deng and colleagues(1) addressed the issue of which patients with Heart Failure will benefit from Heart Transplantation. Since their conclusions may influence both the policy of organisations and the decisions of clinicians about when to refer patients, they should be appraised critically. Can the Heart Failure Survival Score (HFSS) be used to risk stratify potential candidates for heart transplantation? The HFSS was developed to assess ambulatory patients with Heart Failure(2) but Deng applied it to all those listed for transplantation. The model was not used in its original form. Data about intra-ventricular conduction delay was unavailable and in only 16% of cases was peak oxygen uptake data available (this is strongest single predictor of outcome in Heart Failure).(3) This may explain why Deng and colleagues found no difference in survival between low- and medium-risk patients. Does Heart Transplantation improve survival for some patients with heart failure? To achieve this goal candidates must be appropriately selected and the outcome after transplantation must reach accepted standards. Various organisations have provided guidelines on the selection of patients for transplantation - for example those of the American Heart Association(4) - but selection criteria used by Deng and colleagues and the relationship of the patients listed for transplantation to the referral population were not defined. It was difficult to demonstrate any short term survival benefit after transplantation because the survival after transplantation was lower than that reported in either the UK(5) or the International Registry.(6) The reasons underlying this problem are unknown but could involve patient selection, selection and management of organ donors, post-transplant care and organisational issues (such as volume of activity in individual hospitals). Factors which are known to influence the outcome after transplantation, such as pulmonary hypertension,(7) but which are not included in the HFSS were not analysed. From the original study which developed the HFSS,(2) Aaronson and colleagues concluded that patients classified as either medium- or high- risk were likely to benefit from transplantation. In the long term, survival rates after heart transplantation far exceed those which have been reported with pharmacological therapy for Heart Failure.(6, 8) In addition, survival is not the only criterion by which transplantation should be judged. Patients selected because of a low peak oxygen uptake, despite optimum medical therapy, usually have a poor quality of life due to symptoms such as severe breathlessness and fatigue. Such patients are often more than willing to accept the risks of transplantation in exchange for the possibility of a better quality of life and long-term survival. Dr N R Banner
1. Deng MC, De Meester JM, Smits JM, Heinecke J, Scheld HH. Effect of receiving a heart transplant: analysis of a national cohort entered on to a waiting list, stratified by heart failure severity. Bmj 2000;321(7260):540-5. 2. Aaronson KD, Schwartz S, Chen T-M, Wong K-L, Goin JE, Mancini DM. Development and prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplantation. Circulation 1997;95:2660-7. 3. Mancini D, LeJemtel T, Aaronson K. Peak VO(2): a simple yet enduring standard. Circulation 2000;101(10):1080-2. 4. Costanzo MR, Augustine S, Bourge R, Bristow M, O'Connell JB, Driscoll D, et al. Selection and treatment of candidates for heart transplantation. A statement for health professionals from the Committee on Heart Failure and Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association. Circulation 1995;92(12):3593-612. 5. Anyanwu AC, Rogers CA, Murday AJ. Review of the current state of thoracic transplantation: a national prospective cohort study. UK Cardiothoracic Transplant Audit Steering Group. Transplant Proc 1999;31(1- 2):165. 6. Hosenpud JD, Bennett LE, Keck BM, Fiol B, Boucek MM, Novick RJ. The Registry of the International Society for Heart and Lung Transplantation: sixteenth official report--1999. J Heart Lung Transplant 1999;18(7):611-26. 7. Chen JM, Levin HR, Michler RE, Prusmack CJ, Rose EA, Aaronson KD. Reevaluating the significance of pulmonary hypertension before cardiac transplantation: determination of optimal thresholds and quantification of the effect of reversibility on perioperative mortality. J Thorac Cardiovasc Surg 1997;114(4):627-34. 8. Swedberg K, Kjekshus J, Snapinn S. Long-term survival in severe heart failure in patients treated with enalapril. Ten year follow-up of CONSENSUS I. Eur Heart J 1999;20(2):136-9. |
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