Heart Transplantation in Adults With Congenital Heart Disease

Experience With 15 Patients

Abstract

End-stage congenital heart disease (CHD) is an important indication for pediatric heart transplantation (HTx) as well as transplantation in adult populations. The purpose of this retrospective analysis was to compare the survival rate of adults who underwent HTx for end-stage CHD with those who underwent HTx for other causes.

To find out whether HTx is a viable therapeutic option for adult patients with preoperated CHD, data from 15 adult patients with different forms of CHD, who had previously undergone different corrective and palliative procedures, were retrospectively analyzed and compared with the HTx data of 1400 adult patients (>15 years old) whose indications for HTx were other than end-stage CHD.

From 1989 to 2005, 15 adult patients (eight men/seven women) were given transplantation for end-stage CHD. Ten patients had been preoperated once, five patients twice. Their mean age was 34.06 ± 3.9 years. In five cases, patients had development of acute renal failure. One female patient died 40 days after surgery, after having a cerebral infarction; one male patient died 4 years after HTx for OKT 3 monoclonal antibody–resistant rejection; and two patients died as the result of multiple organ failure at 4 days and 30 days after HTx, respectively; 11 patients are still alive. The cumulative survival rate at 1 year is 80% versus 80% in patients given transplantation for noncongenital indications.

Heart transplantation in adults with end-stage CHD can be performed with a good long-term prognosis. Previous palliative operations do not affect outcome after HTx.

Heart transplantation (HTx) has become an important therapeutic option in the treatment of end-stage cardiac diseases. Ischemic and dilative cardiomyopathies are the main indications for HTx in adults. According to the literature, congenital heart disease (CHD) is the cause in 1.5% to 2.4% of heart transplantations in adults.^1,2 Despite previous interventions, 10% to 20% patients with CHD will be candidates for HTx for late myocardial dysfunction, the most common cause of death.³ Over the last few years, the number of HTx performed because of end-stage CHD has increased. Adults with previous corrective and palliative operations and complex anatomy could not formerly undergo HTx because of the increased perioperative risks. Extended operation times would result, theoretically leading to a higher perioperative mortality rate. Advances in patient treatment and surgical techniques have improved survival.

At the Heart Center North Rhine Westphalia (Bad Oeynhausen, Germany), 1400 adult patients underwent HTx between 1989 and 2005. In this retrospective study, we reviewed the pretransplantation and posttransplantation courses of 15 of those given transplantation for end-stage CHD. The purpose of this retrospective study was to illustrate the outcome of surgery in those 15 patients and to relate the outcome to that of patients given transplantation for indications other than CHD.

Patients and Methods

Patient Cohort

We analyzed the data of 15 patients (eight men and seven women) who had undergone HTx for end-stage CHD. Mean age at the time of transplantation was 34.06 ± 3.9 years.

Three patients had attained high urgency status because of rapid decompensation, despite maximum heart failure medical therapy and inotropic support. In four patients, a pacemaker had to be inserted before HTx because of developing bradycardias or high-grade heart blocks. One patient with previous corrective surgery had required pre-HTx support via a ventricular assist device and assisted mechanical ventilation.

Table 1 shows the demographic data of the patients, including pre-HTx diagnosis, age at transplantation, number of previous operations, postoperative course, and causes of death.

Table 1: Demographic Data

Operative Procedures and Techniques

In two cases, femoral artery cannulation had to be performed because the ascending aorta was positioned directly behind the sternum. Duration of surgery differed according to the complexity of individual anatomy, the necessity of reconstruction, and the presence or absence of previous corrective or palliative interventions. Postoperative parameters were length of stay in the ICU and hospital, frequency and severity of rejection episodes, and death.

Deep hypothermic cardiac arrest was necessary in one case. Recipient hearts were removed in the usual way, and HTx was performed according to the Shumway technique, under moderate hypothermia (24° to 28°C). Aprotinin (Trasylol) was applied in five patients. In two patients, persistent bleeding after operation necessitated major blood transfusions.

Atrial and vena cava superior reconstructions had to be performed in four patients by using excess donor tissue and patches. In patients with transposition of the great arteries, anastomoses were adequately achieved through mobilization and by obtaining an adequate length of donor aorta and pulmonary artery, as described by Harjula et al.⁴ Like Mayer et al.,⁵ we experienced no problems with the anastomoses.

In our series, there was no discrepancy between donor-recipient height and weight proportion, although some authors suggest accepting oversized hearts from donors with >1.4 weight ratios to prevent postoperative ventricular failure because these recipients may have venous return equivalent to a larger body.⁶

Immunosuppressive Regimen and Treatment of Rejections

All patients were treated according to the standard immunosuppression regimen (triple therapy),⁷ induced by cyclosporine A, azathioprine, and methylprednisolone directly before surgery, followed by intraoperative injection of prednisolone, then continuing after HTx with the triple therapy, gradually reducing and adjusting the dosage according to laboratory determinations. The acute rejections were primarily treated with steroid pulse therapy, 1000 mg/day IV, for 3 days. Refractory rejections were treated with antithymocyte globulin or with specific monoclonal antibodies (OKT 3).

Long-Term Follow-Up of Post-HTx Patients

As usual, diagnosis of rejection is based on clinical findings and electrocardiographic and echocardiographic data. In the first 6 months after transplantation, patients were examined monthly and every 3 months after that for the next half year. Thereafter, examinations were performed every 6 months. Coronary angiographies were performed at 1, 5, and 10 years routinely and sometimes at shorter intervals on suspicion of CAD. Endomyocardial biopsies were performed when rejection was suspected and routinely during the 1-, 5-, and 10-year examinations.

Results

The data of 15 patients (eight men and seven women) operated on for end-stage CHD were analyzed. The youngest patient was 15 and the oldest patient was 60 years old. Mean age at the time of transplantation was 34.06 ± 3.9 years. Patient mean waiting time until HTx was 233.4 ± 64 days (minimum, 4 days; maximum, 727 days).

Mean ischemic time for donor hearts was 218.66 ± 10 minutes (minimum, 145 minutes; maximum, 287 minutes), mean extracorporeal circulation time was 166.93 ± 17 minutes (minimum, 68 minutes; maximum, 316 minutes), mean ventilation time was 1.3 ± 01 days (minimum, 1 day; maximum, 3 days), mean ICU time was 5.26 ± 2.1 days (minimum, 1 day; maximum, 30 days), and mean hospital stay was 27.93 ± 2.2 days (minimum, 4; maximum, 40 days) (Table 2).

Table 2: Characteristics of Operation

Postoperative echocardiography revealed adequate ventricular function in all patients and required further inotropic support. Perioperative mortality rate in our series was 20%. Cumulative survival over 1 year was 80% and over 5 years, 73%.

In our series, none of the patients had early infection; two patients underwent rethoracotomy because of postoperative bleeding and tamponade; five patients presented with acute renal failure, four of whom required hemofiltration.

One neurologic event (intracerebral infarction) occurred in one patient (patient 9) and ended in her death 40 days after HTx. Two patients had development of graft vasculopathy. One of them required percutaneous transluminal coronary angioplasty to the left anterior descending artery and showed a good left ventricular function during the follow-up, whereas the other patient died 4 years after HTx after experiencing an OKT 3 refractory rejection (patient 12). Two other patients also required OKT3 because of steroid-resistant rejections, but they all showed good long-term cardiac function. OKT3 incidence was 20%. Another two deaths occurred 4 days (patient 5) and 30 days (patient 14) after HTx, respectively, because of multiple organ failure.

One patient is stabilized with rapamycine and the other patients still alive are maintained by using the standard regimen of immunosuppression.

Pre-HTx status of patients who died and those who survived was similar. No statistically significant relation therefore exists between the pre-HTx status and the post-HTx outcome.

Four patients required reconstruction of cardiovascular structures with the use of prosthetic patches or donor tissue. None of the patients had to undergo retransplantation. A situs inversus patient with corrected transposition of the great arteries was also successfully transplanted.

Discussion

The indication for cardiac transplantation in pediatric patients with end-stage CHD is rapidly increasing. In a series of patients at the Heart Center North Rhine Westphalia, end-stage CHD represented 27% of the indications for HTx in pediatric patients, whereas it represented only 1.5% to 2.4% of the indications for HTx in adults.^1,2 Dilative cardiomyopathy represents the majority of remaining indications for HTx in pediatrics, whereas in adults, dilative cardiomyopathy and ischemic cardiomyopathy are equally responsible for the main adult HTx patient cohort.

Biatrial anastomosis in orthotopic implantation is most commonly applied because the ischemic time is shorter. Nevertheless, atrial dysfunction caused by size mismatch of atrial remnants and arrhythmias such as sinus node dysfunction, bradyarrhythmias, and AV-conduction disturbances may lead to a necessity for pacemaker insertion.⁸ Bicaval anastomosis decreases the incidence of arrhythmias, the need for a pacemaker, and the risk of mitral or tricuspid regurgitation. However, narrowing of the superior vena cava and inferior vena cava prolongs⁸ ischemic times and makes biopsy surveillance difficult. In patients with CHD who have reached adulthood, evaluation of each individual case is necessary because of the complexity of individual anatomy, necessity of reconstruction, and presence or absence of previous corrective or palliative surgeries. In cases of previous corrective or palliative surgeries, more associated risks result for HTx as a consequence of excessive adhesions and bleeding tendency. Surgery durations accordingly differ in length from one patient to the next.

Specific surgical maneuvers were required to create the normal anatomic configuration. These included the rerouting of venous circulation, pulmonary artery reconstruction, and atrial septation. Adequate donor tissue was taken to facilitate satisfactory reconstruction.

We analyzed the outcome of cardiac transplantation in 15 adult and adolescent patients with terminal CHD. All had undergone transplantation within the period between 1989 and 2005 as a last therapeutic resort. Perioperative mortality rate was 13%. One patient died as a consequence of cerebral infarction, two as a consequence of multiple organ failure. One patient died after 4 years as a consequence of acute rejection resistant to corticosteroid and OKT3 therapy. He had significant graft vasculopathy. Figure 1 shows cumulative survival analysis as a Kaplan-Meier survival function.

Figure 1.: Cumulative survival analysis as a Kaplan-Meier survival function.

Our series has shown that there is no statistically significant relation between pre-HTx status and post-HTx outcome in patients operated on because of terminal CHD. Death after HTx was not significantly influenced by pre-HTx status. The cumulative survival rate was 80% and 73% at 1 and 5 years, respectively. This is comparable to the cumulative survival rate in adult patients transplanted because of dilated and ischemic cardiomyopathy. As already stated by Minami et al.,⁷ from our institute, here the 1-year survival rate is 78%. Lamour and Addonizio⁹ and Jayakumar and Addonizio¹⁰ have published survival rates of 79% and 72%, respectively.

In our patient cohort, in-hospital mortality rate was nevertheless higher (20%) than in-hospital mortality rate in adult patients who had undergone transplantation in our clinic for causes other than terminal CHD. Hasan et al.¹¹ also reported an early mortality rate of four of nine adult patients undergoing HTx for terminal CHD.

The difference between the two patient cohorts regarding early death may be explained by the complex anatomy of patients with terminal CHD and the previous corrective or palliative interventions to which the patients had been subjected, this consequently being associated with risks of adhesions and excessive bleeding, favoring early postoperative complications. Another aspect is the small number of patients available for our retrospective study, not enough for statistically significant comparative purposes. This is a drawback of our study. Another drawback is an absence of patients who had previously undergone the Fontan procedure. Those patients are more demanding when performing HTx because of the complexity of their physiologic anatomy and an absence of experience. Inclusion of such patients could therefore lead to a higher mortality rate.

Nevertheless, we think that improving technical facilities and a better understanding of the hemodynamics in patients with complex cardiac anatomic abnormalities, either with or without palliative and/or corrective interventions, will facilitate decision-making in favor of cardiac transplantation. In the future, perhaps the decision in favor of cardiac transplantation could be made much earlier in patients in whom palliation is not expected to give optimum results or an improvement in quality of life.

Conclusion

Cardiac transplantation, as a last resort for treatment of adult patients with terminal CHD, has a favorable long-term outcome and is comparable with the long-term outcome in adult patients undergoing cardiac transplantation as a result of terminal or ischemic dilative cardiomyopathy. Early death, however, is higher in patients undergoing cardiac transplantation for terminal CHD. This is the result of the associated complex anatomy and the previous palliative and/or corrective procedures, the latter being associated with adhesions and increased bleeding tendencies. A successful outcome can be achieved with careful evaluation of cardiac anatomy and proper selection of surgical techniques. Efforts should be made to achieve perfect patient selection and surgical timing to increase long-term survival.