what happens if the heart won’t start?

Editorial

What happens if the heart won't start?

`What happens if the heart won't start?' is themost common question to me when I am ®nisheddescribing the nature and risks of heart surgery tothe parents of a child about to undergo atransplant procedure or routine cardiac surgery.Obviously there is a big problem if the heartdoesn't start or if the lungs don't work afterand transplant procedure, and more oftenthan not the patient usually dies. Dr Hoffmanand colleagues at the Children's Hospital ofPhiladelphia have provided some importantinformation about their experience with earlygraft failure following lung and heart transplan-tation in children. Their experience includes bothretransplantation and conservative therapy forgraft failure

Graft failure remains the leading cause of deathearly after transplantation of either the heart orlungs in children. According to the pediatricregistry of heart and lung transplantation main-tained by the International Society of Heart andLung Transplantation (ISHLT), the 30-daymortality rate following heart transplantation isabout 15% and varies according to the age of therecipient. Graft failure is the cause of death inabout 30% of cases and `cardiac failure' accountsfor another 10%; it is not clear how cardiacfailure differs from graft failure as the heart is thegraft. Either eliminating, preventing or success-fully treating both graft and cardiac failure wouldhave a major impact both on early and on latesurvival. The ®gures for early mortality after lungtransplantation are similar. The 30-day mortalityrate is approximately 12% and acute graft failureis the underlying cause of death in 40% of cases(1). In addition to mortality there is signi®cantmorbidity from graft failure in those that survive.There may even be an impact on the long-termfunction of the graft as well as the risk ofgraft coronary vasculopathy or bronchiolitisobliterans.

The underlying cause of early graft failurefollowing transplantation can be one or acombination of several factors. The donor may

be unsatisfactory. Although the echocardiogramand the level of inotropic support may be withinacceptable levels, there are times when the donorheart is more susceptible to ischemia owing to apre-existing injury, such as a period of cardiacarrest requiring cardiopulmonary resuscitation.We have found that evaluating the cardiactroponin I level helpful in questionable cases(2). Likewise, the lung may harbor someunderlying pathology not readily apparentduring the initial evaluation that would manifestitself with the ischemia±reperfusion process. Forinstance, there may be a pulmonary contusionthat is not seen on the initial chest X-ray whenthe donor is declared brain dead within 24 h ofpresentation.

The harvest procedure itself is of criticalimportance. However, as long as the basictenets of organ preservation are employed thisshould not result in graft failure. For the heart,these tenets include adequate decompression,rapid induction of diastolic arrest and appro-priate cooling. A number of preservationsolutions are utilized in transplant programsthroughout the world but there is no evidencethat any one has a clear advantage (3). For thelung, the harvest should be accomplished withpretreatment using prostaglandin E1, decompres-sion of the left atrium, a uniform ¯ush with thepreservation solution, and harvest using a gentlein¯ation pressure. Ischemic time is an importantfactor relating to early graft failure (4). Theabsolute safe interval of ischemia for heart orlung transplantation is unknown. However, mostprograms prefer to stay within 6 h for hearttransplantation and 8 h for the lung.

There are recipient factors that can cause earlyorgan failure following heart or lung transplanta-tion. The heart transplant recipient with elevatedpulmonary vascular resistance presents a uniqueproblem: the donated heart may be perfectly ®nebut not able to cope with the challenge ofdelivering an adequate cardiac output througha restrictive pulmonary vascular bed. There are

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now several tools to deal with this problem,including inhaled nitric oxide in addition to theusual measures of hyperventilation, neuromus-cular paralysis, and sedation. Intravenous orinhaled prostacyclin may also be of major bene®t(5). For the lung transplant recipient, thepresence of borderline left-ventricular functionmay impact on the development of interstitialpulmonary edema. This is especially true in thesituation where a somewhat complex cardiacrepair is necessary in conjunction with thelung transplant procedure for a patient withEisenmenger's syndrome. In addition, particu-larly in patients with cystic ®brosis, the presenceof signi®cant infection will clearly effect pulmo-nary function post-transplant. This occurs byway of mechanisms other than the impact ofthe infection per se. If a patient is harboring orcolonized by resistant bacteria or viruses, thismay also lead to early graft failure in animmunosuppressed patient.

Finally, the post-transplant management ofthese patients is critical to the avoidance of earlygraft failure. This is probably more important inlung transplant recipients. It is generally recom-mended that these patients be kept as ¯uid-restricted as possible. In addition, we tend to keeppatients transplanted for pulmonary vasculardisease sedated and paralyzed for 48 h post-transplant because they seem particularly proneto hemodynamic instability. There are some whosuggest the use of inhaled nitric oxide early afterlung transplant for the prevention of reperfusioninjury (6). Several other medications have beenevaluated as prophylaxis against reperfusion

injury experimentally although none are com-monly in use today.

The ®nal and perhaps most important point ofdiscussion regarding this report from theChildren's Hospital of Philadelphia has to dowith the ethical question of appropriateness oforgan allocation. Is it proper to use donor organsfor high-risk transplant procedures such asretransplantation where the long- and short-term outcomes are not as good as with otherpotential candidates? The waiting lists grow, thetime waiting for organs grows, and the number ofdeaths while waiting for organs increase.

The data for waiting time on the transplant list,number of patients waiting, and deaths whilewaiting for donor hearts and lungs for thecalendar years 1996 and 1997 are depicted inTable 1. The registry for the ISHLT has con-sistently found that retransplantation is a riskfactor for mortality following heart or lungtransplantation in adults (7). This is also truefor the registry for pediatric heart transplantation(1). Presumably there were insuf®cient data for asimilar analysis of pediatric lung retransplanta-tion. In addition to these data, individual series ofretransplant procedures for both the heart andlung have shown an increased risk when theretransplant is performed for early graft failure(8±10). Complicating consideration of this entireissue in the ®rst place is the likelihood of an organoffer when the waiting times are currently soprolonged, even in the pediatric age groups.

The report from the Children's Hospital ofPhiladelphia demonstrates outstanding results inthe four patients retransplanted: all survived early

Table 1. Waiting list statistics

Patient age group

, 1 yr 1±5 yr 6±10 yr 11±17 yr

Lung transplantation

1996

New registrants 15 22 31 43

Average days waiting 117 195 n.d. 469

Deaths while waiting 6 4 1 15

1997


Average days waiting 121 190 412 n.d.


Heart transplantation

1996


Average days waiting 78 77 63 113


1997


Average days waiting 71 49 71 72


n.d., no data.

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with two late deaths. This speaks for the expertiseof this center, but does not endorse retransplan-tation for widespread application in the setting ofacute graft failure. Clearly, experience withtransplantation in general and retransplantationspeci®cally is important in establishing goodoutcomes such as this. Contributing to theirability to acquire organs in a relatively shortperiod of time (18 days on average) is the youngage of the recipients, the oldest being 9 yr of age.As per Table 1, the number of patients waitingand the waiting times are shorter in the groupwho are less than 10 yr of age. The etiology ofgraft failure is an important factor in decidingwhether one should attempt retransplantation.We would be very reluctant to retransplant apatient with graft failure owing to acute adeno-virus or other infection resistant to antimicrobialtherapy in the lung graft, for fear that the newgraft would become secondarily infected. Thereprobably comes a time when the acute infection is`burned out' and we are left with an irreparablydamaged lung. One might be able to determinethat with repeated bronchoalveolar lavage or insome cases serial polymerase chain reactiondeterminations. Nonetheless, two patients in theseries from Philadelphia were retransplanted inthis setting without recurrent infection, demon-strating that it can be done and begging thequestion of whether or not it should be done.

There is no clear answer to the ethicalquestions surrounding retransplantation of thelung or heart in patients dying from a failedtransplant. As physicians in the collective organtransplant community we must seek to providethe best survival and quality of life for the organtransplant community as a whole. However, asindividual physicians we must be advocates forthe survival and best quality of life for ourindividual patients. These patients and familiesare charged with a commitment of enormousresources of their own in order that their childmight derive the bene®t of transplantation, oftenuprooting the entire family to move to thetransplant site for months. We demand of ourpatients and families a commitment to follow acomplex course of therapy, including multiplemedications, exhaustive routine follow-up exam-inations, frequent blood sampling, and in somecases dis®guring side-effects from medications.They must do this without fail. These patientsexpect and should receive the same degree of

commitment from the transplant physicians. Theevaluation of the risks and bene®ts of retrans-plantation for these children should be madeirrespective of the issue of organ shortage. It is upto the transplant physicians to ascertain that thepotential bene®ts indeed outweigh the potentialrisks so that a reasonable expectation of a goodoutcome is feasible.

Charles B. Huddleston, MD

Associate Professor of Surgery

Washington University School of Medicine

St. Louis

Missouri

USA

E-mail: [email protected]

References

1. BOUCEK MM, FARO A, NOVICK RJ, et al. The registry ofthe International Society of Heart and LungTransplantation: third of®cial pediatric report±1999.J Heart Lung Transplant 1999: 18: 1151±1172.

2. GRANT JW, CANTER CE, SPRAY TL, et al. Elevatedcardiac troponin I. A marker of acute graft failure ininfant heart recipients. Circulation 1994: 90: 2618±2621.

3. DEMMY TL, BIDDLE JS, BENNETT LE, WALLS JT,SCHMALTZ RA, CURTIS JJ. Organ preservation solutionsin heart transplantation ± patterns of usage and relatedsurvival. Transplantation 1997: 63: 262±269.

4. YOUNG JB, NAFTEL DC, BOURGE RC and the CardiacTransplant Research Database Group. Matching theheart donor and heart transplant recipient. Clues forsuccessful expansion of the donor pool. J Heart LungTransplant 1994: 13: 353±365.

5. HOEPER MM, OLSCHEWSKI H, GHOFRANI HA, et al. Acomparison of the acute hemodynamic effects of inhalednitric oxide and aerosolized iloprost in primarypulmonary hypertension. J Am Coll Cardiol 2000: 35:176±182.

6. DATE H, TRIANTAFILLOU AN, TRULOCK EP, et al. Inhalednitric oxide reduces human lung allograft dysfunction.J Thorac Cardiovasc Surg 1996: 111: 913±919.

7. HOSENPUD JD, BENNETT LE, KECK BM, et al. Theregistry of the International Society for Heart andLung Transplantation: sixteenth of®cial report±1999.J Heart Lung Transplant 1999: 18: 611±626.

8. DEIN JR, OYER PE, STINSON EB, et al. Cardiacretransplantation in the cyclosporine era. Ann ThoracSurg 1989: 48: 350±355.

9. MICHLER RE, MCLAUGHLIN MJ, CHEN MJ, et al. Clinicalexperience with cardiac retransplantation. J ThoracCardiovasc Surg 1993: 106: 622±631.

10. WEKERLE T, KLEPETKO W, WISSER W, et al. Lungretransplantation: institutional report on a series oftwenty patients. J Heart Lung Transplant 1996: 15:182±189.

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what happens if the heart won’t start?

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