Results and Experience from Bad Oeynhausen

Since the Heart Center in Bad Oeynhausen started its heart transplant program in 1989 a significant number of patients has survived more than 10 years. The transplant activities are embedded in a large cardiac surgery department. Nearly 100 000 operations (97 170), 79 265 with the use of extracorporeal circulation, have been performed up to now. 1 632 heart transplants (HTX), 1 369 implantations of mechanical assist devices (MCS) and total artificial hearts (TAH) demonstrate the busy activities of the dedicated heart failure and transplant unit.

The first heart transplantation by Professor Barnaard was performed December 3rd 1967 in Kapstadt demonstrating its surgical feasibility. But despite immense efforts in various centers, long-term results remained poor. The mean survival time of the first 110 recipients was just 29 days.

At the time of the first heart transplantation in Bad Oeynhausen, March 13th 1989, significant increase of knowledge in organ transplantation was established to achieve reasonable long-term results.

The first patient survived for 13 years and died from cutaneous T-cell lymphoma.

An annual number of 20 transplantations was anticipated but the program expanded quite rapidly culminating in 148 transplants during 1991.

From the beginning, the acceptance of so-called marginal organs was daily practice to expand the donor organ pool. The continuous effort, documented in several publications about the results of transplanting organs of donors with extended acceptance criteria lead to the celebration of the 1 000th transplantation in 1999.

At present, 1 655 pts. (1 351 m/304 f) have received a heart transplant in Bad Oeynhausen. The mean recipient age was 50.1 years (2 days – 77 years) and the mean donor age 33.8 years (1 day – 72 years).

821 pts. are still alive and in regular follow-up by our outpatient clinic.

The predominant underlying diagnosis leading to a transplant indication is dilative cardiomyopathy in 851 cases (51.4 %). The second largest group of patients suffers from coronary artery disease (644 pts./38.9 %). 85 pts. (5.1 %) were transplanted for valvular heart disease, 43 (2.6 %) for congenital heart disease. Over the time, 31 pts. (1.9 %) have been in need for retransplantation.

Although the mean age range was comparable to other centers, a large proportion of recipients was older than 61 years (482 pts.). 19 of these pts. have been older than 71 years at time of HTX. The distribution of donor age is influenced likewise by extended donor criteria. 256 donors have been 51 years and older, 35 of them even older than 61 years. The higher age ranges might have an impact on outcome after HTX.

In addition long transportation times are quite frequent. 224 pts. received their organs exceeding 240 minutes ischemic time. Since this is clearly linked to a worse HTX prognosis the use of the OCS-system has been brought to clinical transportation starting in January 2006. The device maintains stable metabolic conditions by perfusion of the donor heart with oxygenized donor blood and nutrition solution. 28 transplantations could be performed successfully with this new procedure. The present experience includes long-distance explantations in Greece, UK and southern parts of Spain using the conventional cold storage transportation.

Despite high donor and recipient ages and long ischemic time the immunosuppressive protocol is focussing on blocking of IL2-production and expression by various combinations of cyclosporine, tacrolimus, azathioprine, mycophenolate, everolimus, sirolimus and corticosteroids. No induction therapy of any kind is administered in de novo patients.

Modifications take into account that “tailored” patient oriented immunosuppression (IST) should focus on particular problems identified in the individual patient.

Main indication for changes in IST is the severity of rejection diagnosed by endomyocardial biopsy. Although the follow-up schedule is based on non-invasive investigations like clinical examination and course, ECG, echokardiography and laboratory parameters the modification of IST is initiated and controlled by histology.

In selected more severe cases of cardiac rejection (ISHLT II and III) antibody treatment and in some cases plasmapheresis will be added to augment maintenance IST.

One of the major threats for long-term survival is graft failure by graft vasculopathy (GVP).

Every year about 5–10 % of patients are newly diagnosed to develop GVP. Optimal and tailored use of immunosuppressants, preventive treatment of CMV infections and optimized lipid levels in combination with statin treatment may reduce the incidence and ameliorate the course of GVP. It has to be taken into account that modifications of IST should also be optimized concerning renal impairment as a side effect of calcineurin-inhibitors. Overimmunosuppression can also lead to increased number and severity of IST-associated infections.

Another long-term risk of IST is the development of neoplasia (NPL). This was observed in 118 pts. (118 m/10 f) in our center who developed 138 neoplastic disorders. In 14 pts. 2 different NPL and in 3 pts. even 3 different entities could be observed. The incidence in our transplant population is 10.2 % in contrast to about 0.41 % in the general German population. The most common NPL were urological (24.5 %) and dermatological (21 %) diseases followed by pulmonary (17.5 %) and gastrointestinal (15.4 %) tumors.

16 pts. obviously had preexistant malignancies not detected during screening procedures. In this group the worst outcome was observed. 12 pts. died 22.6 months (0.3–84 months) after diagnosis, 4 pts. experienced recurrence of NPL after therapy.

We observed 8.2 % early mortality the leading causes of death being rejection, multi organ failure, graft failure and infection. A different pattern is the distribution of causes for late mortality. In these pts. infection is followed by GVP, rejection and NPL.

In long-term survivors (> 10 years) the majority of pts. expire from GVP and NPL followed by infectious causes.

As commonly known the underlying diagnosis of ischemic heart disease has a negative impact on survival rates. The same effect is observed in case of elder donors and recipients whereas prolonged ischemic times in our cohort did not significantly influence survival rates.

Taking into account that higher donor and recipient rates are reported by the ISHLT to have negative effects on 15-year survival rates it is surprising that especially the long-term results of our cohort demonstrate a trend to better survival rates compared to ISHLT registry data.

Most likely this is due to our very close long-term follow-up regimen supported by a huge transplant specific outpatient clinic.