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Ann Thorac Surg 1996;62:1685-1690
© 1996 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Heart Transplantation: A Single-Center Experience

Klinik für Herz-, Thorax- und Gefäßchirurgie, Deutsches Herzzentrum Berlin, Berlin, Germany

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Background. The success of heart transplantation led to the extension of the criteria for both recipients and donors. The aim of the study was to evaluate the experience with this therapeutic approach for end-stage heart failure at a single center.

Methods. Between April 1986 and January 1996, 1,413 patients were accepted as candidates for heart transplantation. Ventricular assist devices were used as a bridge to transplantation in 173 patients (biventricular assist device in 141 patients and left ventricular assist device in 32 patients). The longest duration of support was 572 days (average, 46 days).

Results. Of the 1,413 patients, 891 underwent heart transplantation (65 children/adolescents and 826 adults; 522 (36%) patients died awaiting a donor heart. The average time spent on the waiting list was 107 days. The average recipient age was 44 years, and the age of donors was extended up to 69 years. Eighty-three patients with ventricular assist devices (48%) subsequently underwent heart transplantation. Twenty-five patients (2.7%) underwent retransplantation. The 30-day mortality rate was 14%, and the overall actual survival at 1, 5, and 10 years was 80%, 59%, and 50%, respectively. Ninty-four percent of patients were in New York Heart Association functional class I or II at 1 year, and 44% returned to work after transplantation.

Conclusions. Despite the broadening of the selection criteria for both recipients and donors, heart transplantation remains an effective treatment for end-stage heart failure. Nevertheless, this therapeutic approach is severely limited by a considerable disparity between the need and availability of donor organs.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Orthotopic heart transplantation is an established therapy for end-stage heart disease, which provides good long-term results. The initial clinical success of heart transplantation led to the revision of the once-rigid selection criteria for potential recipients and donors. Nevertheless, the shortage of donor organs remains the most limiting factor in heart transplantation, causing a steady increase in the time spent on the waiting list [1, 2]. New strategies for enlarging the donor pool have been developed, such as accepting donors more than 55 years of age, extending the permissible ischemic time to more than 4 to 6 hours, accepting greater mismatches between donor and recipient body weight, using hearts obtained from recipients of heart-lung transplants who do not have end-stage right-sided heart failure (the so-called domino operation), or even performing coronary artery bypass on a donor heart during transplantation or reusing an already transplanted heart [3–9]. Such liberal selection criteria, including those for the extended use of circulatory assist devices as a bridge to heart transplantation, have been used for both recipients and donors at our institution since its inception in April 1986 [10–12]. The aim of this study is to evaluate our early and long-term results of this therapeutic approach for end-stage heart failure.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Between April 1, 1986, and January 15, 1996, 1,413 patients were accepted as candidates for heart transplantation. Ventricular assist devices were used as a bridge to transplantation in 173 patients (biventricular assist device in 141 patients and left ventricular assist device in 32 patients), the longest duration of support being 572 days (average, 46 days). Biventricular support was carried out using the pneumatically driven paracorporeal Berlin Heart assist device. The left ventricular support devices used were totally implantable: the electromagnetically powered Novacor device (Baxter Healthcare, Oakland, CA) in 26 and the pneumatically powered TCI HeartMate (Thermo Cardiosystems Inc, Woburn, MA) in 6 patients. Adult patients with mechanical circulatory support were considered for heart transplantation if end-organ failure except heart function had completely recovered and the patients were free from infections and had normal or near-normal immune competence. In the pediatric group of patients, ventilator support or persistent renal failure necessitating continuous hemofiltration or dialysis were not contraindications for heart transplantation.

The average recipient age was 44 years. The age of donors was extended up to 69 years, with a mean age of 33 ± 14 (standard deviation) years (range, 0.01 to 69 years; median, 32 years). Graft ischemic time was 172 ± 47 (standard deviation) minutes (range, 64 to 385 minutes; median, 171 minutes).

Donor Availability
The heart donors were obtained through a cooperative agreement with the Eurotransplant Organization from Leiden, the Netherlands, or from hospitals where our transplant coordinator managed organ donation (so-called local donor).

Operative Technique
All operations were performed according to the standard technique of Lower and Shumway [13, 14] with the modified incision of the right donor atrium for the anastomosis. This technique includes the use of conventional cardiopulmonary bypass, with resection of the diseased heart at the level of both atria, leaving behind the atrial posterior walls and the stumps of aorta and pulmonary artery [12]. The donor hearts were arrested with 2,000 or 3,000 mL of cold Bretschneider's cardioplegic solution, which was initially infused at a pressure of 80 to 100 mm Hg until cessation of the heart contractions and subsequently by gravity over an 8- to 12-minute period. The donor heart was explanted by transecting both caval veins and the four pulmonary veins after dividing the ascending aorta and the pulmonary artery, preserving the sinus node, its artery, and the sinoatrial pathways. All donor hearts were stored in cold cardioplegic solution during transportation. The right atrium was incised longitudinally beginning in the inferior caval vein ostium and curving slightly toward the right atrial appendage. The implantation procedure was begun with the left and right atrial anastomoses with continuous 3-0 polypropylene suture, followed by pulmonary artery and aortic anastomoses with 4-0 polypropylene suture. A dual-chamber telemetric pacemaker was routinely implanted for postoperative monitoring of acute rejection through measurements of the intramyocardial electrogram amplitude [15].

Immunosuppression
Immunosuppression was induced by triple-drug therapy: cyclosporine (at a dose sufficient to maintain a whole-blood level of 250 to 350 ng/mL [monoclonal antibody] or 600 to 900 ng/mL [polyclonal antibodies] during the first 3 months and to maintain it at a level greater than 180 ng/mL [monoclonal antibody] during the late postoperative period), azathioprine (2 to 3 mg/kg of body weight per day), and prednisone (presently, 1.0 mg/kg per day for the first 10 days, followed by successive dose reductions to 0.3 mg/kg per day by the third week and 0.15 mg/kg per day within 60 days after transplantation). Methylprednisolone (1,000 mg) was administered before the aortic cross-clamp was removed. Until 1992, rabbit antithymocyte globulin (1.5 mg/kg per day) was administered intravenously for the first 4 days after the operation. Since July 1992, this therapy has been administered according to the results of T-cell and monocyte human lymphocyte antigen class II antigen measurements. Endomyocardial biopsies were not routinely performed. Acute rejection was monitored noninvasively by telemetric (day by day) intramyocardial electrocardiography, echocardiographic examinations, and (if indicated) occasionally by endomyocardial biopsy [15]. Episodes of acute rejection were treated by high-dose steroids alone (500 mg of methylprednisolone intravenously for 3 to 5 days) or in combination with rabbit antithymocyte globulin or murine monoclonal T3-cell antibodies (OKT-3).

Follow-up
After a patient has undergone a pretransplantation evaluation at our facilities, our transplant team, composed of transplant physicians, cardiologists, surgeons, a pulmologist, and a psychologist, provides or coordinates subsequent periodic medical evaluation and early and long-term posttransplantation patient care. Generally patients are referred to us for further diagnostic and therapeutic management if major complications develop during the follow-up period. There is a complete follow-up of all patients after heart transplantation, and none has been lost to follow-up.

Statistical Analysis
Long-term survivals were calculated by the Kaplan-Meier method and compared with the log-rank test. A value of p less than 0.05 was considered to be significant.

	Results

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
During the period of almost 10 years (April 1, 1986 to January 15, 1996) 891 patients (pediatric heart transplantation, n = 65; adults, n = 826) have undergone heart transplantation at our institution; 522 patients (36%) died while on the waiting list. The number of heart transplantations represents a 4.1% of all open heart procedures (n = 21,968) performed at our institution during this period. Eighty-two percent of the transplant recipients were male, and only 18% were female. The average time spent on the waiting list was 107 days. Eighty-three patients with ventricular assist devices (48% of all patients who received a ventricular assist device) subsequently received a heart transplant. Twenty-five patients (2.7% of all patients who received a transplant) underwent retransplantation.

The annual transplantation rate has reached a plateau. The number of orthotopic heart transplantations has remained fairly stable at around 100 per year but with a slight decline during the last several years (Fig 1). Preoperatively, the majority of the heart recipients had had dilated cardiomyopathy (64.3%) or end-stage ischemic heart disease (30.5%) (Fig 2). In the last several years there was a slight tendency for an increase in the percentage of patients with end-stage coronary artery disease (Fig 3).

View larger version (28K): [in this window] [in a new window]   Fig 1. . Heart transplant volume (1986 through 1995).

View larger version (13K): [in this window] [in a new window]   Fig 2. . Adult heart transplant indications. (Re-Tx = retransplantation.)

View larger version (18K): [in this window] [in a new window]   Fig 3. . Adult heart transplantation indications.

The overall 1-, 5-, and 10-year actual survival rates for all patients including pediatric patients, patients on mechanical circulatory support preoperatively, and patients having retransplantation were 80%, 59%, and 50%, respectively (Fig 4). Ninety-four percent of patients were in New York Heart Association functional class I or II at 1 year, and 44% returned to work after transplantation.

View larger version (16K): [in this window] [in a new window]   Fig 4. . Actuarial survival of patients receiving a heart transplant including pediatric patients, those having retransplantation, and transplant recipients after mechanical circulatory support.

View larger version (18K): [in this window] [in a new window]   Fig 5. . Actuarial survival by era (log-rank test, p = 0.0001).

View larger version (21K): [in this window] [in a new window]   Fig 6. . Actuarial survival by recipient age (log-rank test, p = 0.10).

View larger version (20K): [in this window] [in a new window]   Fig 7. . Actuarial survival by donor age (log-rank test, p = 0.99).

View larger version (19K): [in this window] [in a new window]   Fig 8. . Actuarial survival of patients receiving a heart transplant after mechanical circulatory support (log-rank test, p = 0.05).

View larger version (20K): [in this window] [in a new window]   Fig 9. . Actuarial survival after retransplantation (log-rank test, p = 0.000).

	Comment

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

The results achieved at our institution reflect the current state of heart transplantation performed worldwide [16–18], and they are in most variables comparable with the results of the Registry of the International Society for Heart and Lung Transplantation [16]. The major difference between our results and the International Society for Heart and Lung Transplantation Registry was the indications for heart transplantation. At 30.5%, the percentage of transplant recipients with coronary artery disease at our institution was significantly less than the 46.4% documented in the International Society for Heart and Lung Transplantation Registry. There are two possible factors for this difference. The first is our policy of extended use of mechanical circulatory support devices, primarily biventricular pumps, which were almost exclusively implanted in patients with dilated cardiomyopathy and therefore increased their percentage in the total number of heart recipients. Eighty-three patients, approximately 10% of our 891 heart transplant recipients, had been successfully bridged to transplantation. Most of them had dilated cardiomyopathy, and therefore the total number of transplant recipients with nonischemic cardiomyopathy was increased. The second factor is our restrictive indications for transplantation in patients with end-stage coronary artery disease [11, 19]. Due to donor shortage, we have adopted the policy of performing coronary artery bypass grafting instead of primary transplantation in patients with terminal coronary artery disease and angina pectoris symptoms despite the presence of severely depressed left ventricular function (left ventricular ejection fraction of 0.10 to 0.25). With acceptable operative mortality of less than 10% and excellent late results [19], this strategy reduced the number of potential heart transplant candidates and consecutively lowered the already high mortality rate of patients awaiting transplantation. Our current policy is that there is rarely an indication for heart transplantation in coronary artery patients with a left ventricular ejection fraction greater than 0.20 and angina pectoris. Even in patients whose left ventricular ejection fraction was less than 0.20, coronary artery bypass grafting offered an acceptable alternative to heart transplantation, yielding long-term results as good as those after primary heart transplantation (in regard to late survival) with the advantages of not necessitating immunosuppressive therapy and of reducing the need for postoperative surveillance [11]. The 669 patients with end-stage coronary artery disease and depressed left ventricular function (left ventricular ejection fraction, 0.10 to 0.25) operated on at our institution during the 10-year period represent 6% of the total of 11,215 isolated coronary artery bypass operations performed in our institution between April 1986 and January 1996.

Similarly to the situation worldwide, the increased demand for cardiac transplantation in the face of a relatively fixed supply of donor hearts has forced us to increase the availability of hearts for transplantation and to accept cardiac allografts from "high-risk" donors since the beginning of our heart transplantation program [10]. Based on prolonged ischemic time and extended donor age, far more than 50% of our cardiac allografts came from "high-risk" donors. At present our policy is to accept a heart from an old donor if the heart function is excellent. Our oldest accepted heart was from a 69-year-old donor and continues to function well. However, it is logical to assume that these hearts have a lower functional reserve, both immediately after implantation and during the late postoperative period. Therefore, we implanted hearts from older donors in patients of similar age or in patients put on the "special urgency list" for heart transplantation. Because coronary angiography is often not available, we accept such hearts after meticulous assessment of the patient's history and standard electrocardiographic and echocardiographic findings, and after extraordinarily meticulous inspection and palpation of the heart and particularly coronary arteries by an experienced surgeon, ensuring that the heart function is excellent and the coronary arteries are free of gross atherosclerotic plaques or calcification. Although this policy poses the risk of overlooking a preexisting coronary artery lesion, these could be treated by angioplasty or even coronary artery bypass grafting in the late period, if present. Our results indicated that recipients with transplants from donors older than 55 years were somewhat more susceptible to primary graft failure, but their 5-year survival rate was similar to that of recipients whose transplants came from donors younger than 55 years. Although these midterm results of the two groups are comparable, it might be presumed that the late survival of recipients with older donor hearts will not be as good as that of patients with hearts from younger donors, not only because of aged transplants but also due to several other reasons such as the older age of recipients of these organs and polymorbidity of this group of patients. However, despite a possible reduced late survival, the policy of using hearts from older donors is still a better alternative then accepting increased pretransplantation mortality and waiting for an ideal donor heart.

In conclusion, despite the extension of selection criteria for both recipients and donors, heart transplantation remains an effective treatment for end-stage heart failure. However, this therapeutic approach remains severely limited by a considerable disparity between the need for and availability of donor organs.

	Acknowledgments

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
We are indebted to Dr Stefanie Heins, Heidi Kriegler, Jonathan Davis, and Norbert Franz for assistance in preparing the manuscript.

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Presented at the Poster Session of the Thirty-second Annual Meeting of The Society of Thoracic Surgeons, Orlando, FL, Jan 29–31, 1996.

Address reprint requests to Dr Pasic, Klinik für Herz-, Thorax- und Gefäßchirurgie, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany (e-mail: pasic{at}DHZB.DE).

	References

Top Footnotes Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 

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3. Pflugfelder PW, Singh NR, McKenzie FN, Menkis AH, Novick RJ, Kostuk WJ. Extending cardiac allograft ischemic time and donor age: effect on survival and long-term cardiac function. J Heart Lung Transplant 1991;10:394–400.[Medline]
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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Miralem Pasic Matthias Loebe Yuguo Weng Roland Hetzer Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pasic, M. Articles by Hetzer, R. Search for Related Content PubMed PubMed Citation Articles by Pasic, M. Articles by Hetzer, R.