Cardiac Transplant Program Research Articles

Early transient multivalvular regurgitation detected by pulsed Doppler in cardiac transplantation

Use of pulsed Doppler to detect and evaluate cardiac valvular regurgitation is an accepted noninvasive diagnostic method. 1 Since the cardiac transplantation program started at our institution, 8 consecutive patients have been prospectively studied by pulsed Doppler. This report provides the first description of valvular function in the transplanted heart.

Donor Availability as the Primary Determinant of the Future of Heart Transplantation

Heart transplantation has now achieved a therapeutic status similar to that of cadaveric renal transplantation. Depending on patient selection criteria, it is estimated that as many as 15,000 people per year could conceivably benefit from a heart transplant, but the actual number of persons who will benefit is severely constrained by donor supply. Availability of heart donors was estimated based on data obtained on 1,955 organ donors in the United States. The results show that because of age and other contraindications, only 400 to 1,100 viable donor hearts may be available each year. Donor supply is the most critical determinant of the future of heart transplantation since it will dictate the number of transplants performed, the survival of transplant recipients, the total program expenditures associated with heart transplantation, the nature of the legal and ethical issues involved, the number of cardiac transplant programs required to make optimal use of the available donor hearts, and the future role of mechanical circulatory support systems.

The Cardiac Donor: A Six-Year Experience

From March 1, 1979, to March 1, 1985, the University of Arizona received 223 cardiac donor referrals. Sixty-two were accepted: 15 local, 23 regional (less than 370 km or 200 nautical miles), and 24 distant (370 to 1556 km or 200 to 840 nautical miles). Thirty-eight donor deaths were due to motor vehicle accidents, 10 to gunshot wounds, 6 to cerebral disease, and 8 to other closed-head lesions. The mean time from injury to brain death was 65 ± 5 hours (± standard error of the mean [SEM]) and from brain death to organ donation, 12 ± 3 hours. The mean ischemic time for the donor hearts ranged from 30 to 233 minutes (mean ± SEM, 128 ± 7 minutes). Fifty patients, otherwise acceptable, were refused as cardiac donors because an ABO-compatible recipient was not available. Two regionally procured hearts failed at operation, 1 because of unrecognized donor sepsis and 1 from a patient on large-dose inotropic support. Although there was no difference in myocardial function, median survival with follow-up through June 30, 1985, of patients receiving locally, regionally, and distantly procured organs was 59 months, 18 months, and 21 months, respectively. Cumulative proportion 1-year survival was 93%, 56%, and 61%, respectively. The 2-year survival was 85% for patients given locally procured hearts, 43% for those with regionally procured hearts, and 38% for those with a heart from a distant donor. Survival curves showed significantly longer survival for locally procured organs than regionally or distantly procured organs ( p < 0.05). Distant procurement of cardiac organs, although expanding the donor pool, is associated with decreased long-term recipient survival, and donor ischemic time appears to be the significant variable. Regionalization of cardiac transplantation programs should increase the frequency of donor usage by providing appropriate recipients for locally obtained donor organs and, at the same time, reduce donor ischemic time.

Role of cardiac transplantation in the management of congestive heart failure

T he successful treatment of end-stage congestive heart failure by transplantation has not received wide acceptance until recently. Cardiac transplantation originated with Carel and Guthrie in 1905 [1]. These innovative experimenters reported successful heterotopic procedures in dogs, resulting in the awarding of the Nobel Prize in medicine to Carel in 1912. Following this pioneering work, there were only scattered reports in the literature regarding cardiac transplantation. The modern era of heart transplantation was initiated by Shumway, professor of cardiac surgery at Stanford University Medical Center. In 1960, Shumway and Lower, chairman of cardiac surgery at the Medical College of Virginia, reported the first successful orthotopic cardiac transplantation procedure performed in the canine model [2]. The initial clinical heart transplantation procedure was performed in 1967 by Bernard in Capetown, South Africa [3]. This sparked an initial enthusiasm resulting in the performance of more than 150 transplant procedures over the next two years. However, because the one-year survival rate was less than 20 percent, enthusiasm in the medical community and among the public rapidly faded. However, Shumway believed that this operation could restore patients to a full life and be a therapeutic adjunct to the treatment of end-stage congestive heart failure. He continued his cardiac transplantation program, with a gradual increase in patient survival [4]. After the introduction of cyclosporin, a potent immunosuppressive agent, survival further increased, resulting in a revival of cardiac transplantation as a therapeutic procedure both in the United States and around the world. The current one-, two-, and three-year survival rates with cyclosporin are 80, 78, and 70 percent, respectively. Fiveyear follow-up in cyclosporin-treated patients is unavailable. This renewed interest in transplantation resulted in the proliferation of more than 30 transplant centers, which performed 270 transplantation procedures in 1984. Most patients currently referred for cardiac transplantation have terminal cardiac disease due to primary cardi0myopathy or ischemic heart disease with global left ventricular function. Recipient selection is an important aspect in any program. The upper age limit for transplant recipients has been increased due to better immunosuppression. Most institutions now accept patients for potential transplantation up to the age Of 55. All patients have class IV symptoms and have an expected survival of less than one year. These patients, however, should be otherwise healthy without irreversible end-organ disease. Patient compliance, motivation, and strong family support represent important psychosocial criteria. Contraindications to heart transplantation include systemic disease, irreversible end-organ disease, pneumonia, and recent pulmonary infarction. This latter contraindication represents a temporary one, until chest roentgenography shows resolution of the infarct area. Additional contraindications include a history of alcohol or drug abuse, mental illness, or cancer. Elevation of pulmonary vascular resistance above 8 Wood units also represents a contraindication to orthotopic cardiac transplantation, but may actually be an indication for heart-lung transplantation. Cardiac donors are limited to younger persons, usually less than 35 years of age for males and 40 years of age for females. This limitation is based upon retrospective analysis of donor age that revealed a significant correlation between the development of coronary atherosclerosis in the grafted heart and the age of the donor. In addition, the donor should have no evidence of systemic infection, chest trauma, or prolonged cardiac arrest. Potential heart donors should be hemodynamically stable without high-

Psychiatric aspects of heart transplantation: preoperative evaluation and postoperative sequelae.

The contribution of a liaison psychiatrist to a cardiac transplant programme is described. Ninety one patients were referred to the transplant unit for assessment over four years, and of these, 86 were assessed by the psychiatrist. A high prevalence of preoperative anxiety and depression was found. Thirty four transplants were performed on 33 patients during the study and 22 patients survived. Six patients developed transient delirious episodes during the first 10 postoperative days, three showed symptoms of considerable anxiety, and three developed social and behavioural problems during the convalescent period. Subjects with higher scores on the somatic scale of the general health questionnaire showed increased postoperative mortality. In conclusion, the liaison psychiatrist is useful in evaluating and managing heart transplant patients before and after operation.

Cardiac Transplantation at the Texas Heart Institute: Comparative Analysis of Two Groups of Patients (1968–1969 and 1982–1983)

Two groups of heart transplant recipients were studied. Patients in Group 1 underwent heart transplantation from May, 1968, to November, 1969. They were compared with Group 2, a series begun in July, 1982, when the current cardiac transplantation program was renewed at the Texas Heart Institute, and terminated in December, 1983. Patient selection, management, and results were compared. With a cumulative follow-up of 64 patient-months (Group 1) versus 93 patient-months (Group 2), the actuarial 18-month survival was 0 in Group 1 versus 70% in Group 2. Nine of the 18 patients in Group 1 died of rejection versus 4 of the 18 patients in Group 2. There were 6 infection-related deaths in Group 1 and none in Group 2. Using linearized rates based on 100 patient-months, the incidences of rejection and infection were, respectively, 23 versus 10.7 ( p < 0.05) and 64 versus 34 ( p < 0.05) between Groups 1 and 2. Incidence, pattern, and severity of these major complications have been reduced significantly. Over the last decade, there have been improvements in the selection of potential candidates, better management of donors, improved graft preservation, and the introduction of more selective immunosuppression.

Orthotopic cardiac transplantation in a Veterans Administration hospital.

Of 57 patients referred to the McGuire Veterans Administration Medical Center, Richmond, Va, for evaluation for cardiac transplantation, 18 received allografts. The overall graft survival rate was 67% from two to 24 months after transplantation. In 15 recipients receiving immunosuppression with rabbit anti-human thymocyte globulin, prednisone, and azathioprine, previous transfusion and HLA-DR matching resulted in improved graft survival. In three patients receiving cyclosporin and prednisone, hypertension, nephrotoxicity, and hepatotoxicity were seen. All surviving recipients were in functional New York Heart Association class 1 or 2. The cost to the Medical Center was $23,275 per transplant. The results achieved at the center suggested that a regionalized cardiac transplant program can be established within the VA health care system with acceptable clinical results and significant financial savings.

Nocardial infections in the immunocompromised host: A detailed study in a defined population.

A retrospective, clinical, epidemiologic, and risk-factor analysis was performed on 21 recipients of cardiac allografts who had experienced nocardiosis since the inception of the cardiac transplantation program at Stanford University Medical Center in 1968. The lung was the primary and only detectable site of infection in 17 (81%) of 21 patients, and there were three cases of disseminated disease. Presenting symptoms were either nonspecific (dry cough and fever) or absent (in 40%). The time of onset of infection following transplantation was variable (range, 43-982 days), and there was no period of peak incidence. Epidemiologic and risk-factor analysis failed to identify a nosocomial point-source or specific parameters that predisposed a patient to nocardial infection. Nocardiosis was not associated with the onset of primary infection with cytomegalovirus following transplantation. However, an association between pulmonary nocardiosis and subsequent development of nontuberculous mycobacteriosis was established in five of the 21 patients. All patients with nocardiosis were treated primarily with sulfisoxazole (6-12 g per day) for a mean of 13.2 months. No deaths were attributable to nocardial infection, nor could acquisition of the infection be shown to affect overall survival. The results of the study support an aggressive approach to diagnosis of infections in the immunocompromised host and suggest that a favorable therapeutic outcome may be anticipated in such individuals who sustain nocardiosis if the diagnosis is made early in the course of the infection and if appropriate antimicrobial therapy is instituted.

Intracranial infection in cardiac transplant recipients.

Infections have produced most of the deaths in the Stanford cardiac transplant program. Of the first 182 transplant recipients, 27 developed nonviral intracranial infections: meningoencephalitis/abscess in 16 patients, meningitis in 9, and rhinocerebral phycomycoses in 2. The responsible organisms included aspergillus, toxoplasma, candida, klebsiella, cryptococcus, coccidioides, listeria, mucor, and rhizopus. Characteristically, the areas of meningoencephalitis and abscesses were multiple and deep seated. Intracranial infections were invariably associated with pulmonary or disseminated infection with same organism. Computed tomographic (CT) brain scans in patients with meningoencephalitis often showed minimal, nonspecific, low-density lesions which usually did not exhibit contrast enhancement. At surgery the lesions were found to differ from typical pyogenic abscesses in that capsules were not well developed, and the aspirate consisted of necrotic fragments of edematous white matter and inflammatory cells rather than liquefied pus. Aspergillus infections of the central nervous system usually developed within the first three months after transplantation. Cases of meningitis occurred at variable times after transplantation, but approximately half appeared within 30 days after immunosuppressive therapy for treatment of rejection was increased. The prognosis for brain abscess depended on the causative organism. All patients with aspergillus infection died despite treatment with amphotericin B. The toxoplasma abscess responded to a combination of sulfadiazine and pyrimethamine. Meningitis was successfully suppressed or cured with appropriate treatment except for 1 patient with disseminated cryptococcosis.

Aspergillus Infection Complicating Cardiac Transplantation

During the initial two-year period of the cardiac transplant program at Stanford University Hospital, a 28% incidence of invasive pulmonary aspergillosis was observed. The diagnosis was based on postmortem findings in two patients, and on isolation of the fungus from percutaneous lung aspirates or transtracheal aspirates in the other three.Aspergilluswas isolated from multiple cultures of sputum from four of the five patients. Local or systemic amphotericin B therapy or both was administered to three patients, and in two of them long-term treatment and necessary. Among the multiple underlying predisposing factors responsible for the high incidence of aspergillosis in cardiac transplant patients, pulmonary factors relatively unique to cardiac transplantation as well as immunosuppression appeared to play major roles.