An Intervention Trial for Strengthening Medical Adherence after Heart Transplantation.

INTRODUCTION: In heart transplant recipients, nonadherence is associated with higher risk of morbidity and mortality. RESEARCH QUESTION: Can a psychoeducational intervention enhance adherence to medical recommendations? DESIGN: We randomized 200 patients awaiting heart transplantation on the high urgency wait list to a manualized psychoeducational intervention or standard care. Follow-up continued to three years after transplantation. Primary endpoint was adherence to immunosuppressive medication, assessed at 3, 6, 12, 24, and 36 months posttransplant. Secondary endpoints were barriers to adherence during follow-up and clinical outcomes, including cardiac rejection within the first postoperative year and postoperative 3-year mortality. RESULTS: Fifty patients died before or within the first 3 months of transplantation. The primary endpoint was analyzed in 66 patients in the intervention group and 66 in the control group. Both study groups showed almost maximal adherence to immunosuppressive medication throughout follow-up, with no significant time x treatment interaction (P>0.99). Likewise, there was no significant time x treatment interaction (P=0.41) on barriers to adherence. The percentage of patients with International Society for Heart and Lung Transplantation standard grade 1 and 2 rejection was in the intervention and control groups 82.5% and 78.7%, respectively, and 8.8% and 13.1%, respectively, without significant differences between study groups (P=0.75). Considering all randomized and transplanted patients in the intervention group (N=85) and control group (N=87), postoperative 3-year mortality was 29.4% and 27.6%, respectively (P=0.82). CONCLUSIONS: Adherence to immunosuppressive medication was high, even without a complex, manualized psychoeducational intervention. The intervention had no significant positive impact on cardiac rejection and mortality.

Heart transplantation at the Heart Center North Rhine-Westfalia.

At the Heart Center North Rhine-Westfalia, Germany, more than 1,500 adult cardiac transplantations and more than 100 pediatric cardiac transplantations have been performed since the transplant program was initiated in 1989. Each year, we take care of 800 cardiac transplant recipients and 1,700 patients with heart failure who are in a long-term program for cardiac transplantation or on the Eurotransplant waiting list for cardiac transplantation. We have experience with ventricular assist device implantation as bridge to transplant in more than 300 patients. In total, our clinical know-how with cardiac transplant recipients is based on 10,800 patient-years of observation. In 2006, we transplanted the first donor heart worldwide with the Organ Care System, a technology capable of maintaining human organs in a functioning state ex-vivo. Usually, our transplant recipients have more preoperative risk factors than cardiac transplant recipients at other German heart centers. Our postoperative patient care is individualized with respect to immunosuppression and the performance of myocardial biopsies and coronary angiography. Since 1989, we have performed 31 cardiac retransplantations.

Frequent detection of hepatitis B core antibodies in heart transplant recipients without preceding hepatitis B infection.

It is unclear whether heart donors positive for hepatitis B core antibodies (anti-HBc) can transfer hepatitis B virus (HBV) infection to immunosuppressed heart recipients, or whether passive transfer of anti-HBc simulates a hepatitis B infection. Therefore, we performed a case-controlled study in 46 heart recipients who all tested negative for hepatitis B antigen (HbsAg), antiHBc, and hepatitis B surface antibodies before heart transplantation. Twenty-three patients (group 1) received hearts from anti-HBc-positive donors, while 23 other patients (group 2) received hearts from anti-HBc-negative donors. After heart transplantation, anti-HBc were present in 65.0% of blood samples among group 1 and 47.8% of the blood samples among group 2 (P > .05). HbsAg was undetectable in blood samples of all patients of both study groups. The immunoglobulin preparation that we regularly use for immune suppression immediately after heart transplantation contained a relatively high concentration of anti-Hbc antibodies. The nearly identical presence of anti-HBc in both study groups indicated that passive transfer via immunoglobulin preparations rather than HBV infection is the cause for the anti-HBc detected in heart recipients. Since only a small volume of blood is transferred with the donor heart, it seems to be rather unlikely that the donor heart might be the source of anti-HBc. In summary, we observed no evidence for HBV infection in those heart recipients who received organs from anti-HBc-positive donors. Moreover, our data demonstrated that the presence of anti-HBc in heart recipients frequently occurs but does not necessarily indicate a preceding HBV infection.

Organs from donors with primary brain malignancy: the fate of cardiac allograft recipients.

BACKGROUND: The phenomenon of malignancy transmission from donors with primary brain malignancy (PBM) which is relatively well documented in renal or liver transplant recipients, has not been analyzed in cardiac allograft recipients. METHODS: We reviewed the medical records of 32 cardiac allograft recipients who were transplanted with organs from donors suffering from primary brain malignancies from 1989 to 2003. RESULTS: No case of donor-transmitted malignancy has been reported with a mean follow-up of 80.6 months. CONCLUSIONS: In our experience as well as according to a review of the literature, the risk of tumor transmission from donors with primary brain malignancy to cardiac allograft recipients seems to be extremely low. In the context of the increased donor shortage, we recommend to accept all suitable cardiac allografts harvested from donors with primary brain malignancy provided there are no detectable remote metastases.

Influence of different assist devices on survival after orthotopic heart transplantation.

BACKGROUND: In 1995, a risk factor of 1.88 was indicated for one-year mortality in connection with bridging to heart transplantation. Both one-year and three-year survival rates in patients bridged to transplantation were less than 80%. METHODS: From 3/89 to 12/98, 903 orthotopic heart transplantations were performed at our center in 888 recipients. Bridging was necessary in 142 patients. RESULTS: The one-year survival rate was 76% in pts without VAD, 86% in pts bridged with VAD and 66% in pts with VAD due to postcardiotomy syndrome. The three-year survival rates were 73%, 80% and 55% respectively. CONCLUSIONS: Early and late results in patients bridged to transplantation remarkably improved over 1995. One-year and long-term survival rates are significantly lower when assist devices are used in patients with postcardiotomy syndrome. Despite a high incidence of assist-related complications, electively bridged patients showed significantly better early and long-term results than the control group.

Altered levels of mRNA of apoptosis-mediating genes after mid-term mechanical ventricular support in dilative cardiomyopathy--first results of the Halle Assist Induced Recovery Study (HAIR).

BACKGROUND: Ventricular assist devices (VADs) lead to an immediate unloading of the failing heart. Although VADs are used as a bridge to transplant, in some cases patients suffering from dilated cardiomyopathy have been weaned from the VAD without transplantation after a recovery process initiated by the cardiac support. Myocardial apoptosis is associated with inadequate myocardium and might be reverted during VAD support of the failing heart. Therefore we measured transcription of apoptosis-associated genes FasExo6 Del, Fas-receptor, and Bcl-xL as markers of a putative recovery. METHODS: Fas-receptor, its soluble isoform FasExo6Del, and Bcl-xL mRNA were quantified by standard calibrated competitive reverse-transcription polymerase chain reaction (PCR) in 6 patients suffering from dilated cardiomyopathy. RNA standards were prepared by introducing 100 bp deletions into the native cDNA, resulting in truncated PCR products with identical primer-binding sites. Standards were transcribed in vitro and the resulting RNA was quantified. RESULTS: Transcription of apoptosis-inhibiting genes FasExo6 Del and Bcl-xL were upregulated in patients supported for more than 6 weeks. Fas receptor mRNA remained unaffected by VAD support. CONCLUSIONS: Transcriptional upregulation of apoptosis-inhibiting genes might be caused by a desensitization to apoptotic stimuli and might indicate a relaxation of the diseased status of the myocardium. These data outline the first biochemical evidence of a remodelling process occurring in supported ventricular myocardium.

Hemodynamic follow-up of cardiac allografts from poisoned donors.

BACKGROUND: The current shortage of donor organs, combined with an increasing demand for cardiac allografts, means that extended donor criteria are becoming more and more accepted. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion; few data are currently available in the medical literature. We describe our experience with 19 orthotopic heart transplant recipients of organs from donors after acute intoxication with different agents. METHODS: Between March 1989 and December 1997, 883 orthotopic heart transplantations were performed at our transplant unit. Within this group, we accepted donor hearts after ethanol intoxication (n=1), benzodiazepine (n=1), alkylphosphate (E 605) in combination with beta-blocker intoxication (n=1), carbon monoxide poisoning (n=5), digitalis (n=1), digitalis/glibenclamide (n=1), chlormethiazole (n=1), propoxyphene (n=1), alkylphosphate (E 605) (n=1), insulin (n=2), neprobamate/ thiocyacide/flurazepam (n=1), paracetamol (n=1), carbamazepine (n=1), and cyanide (n=1) intoxication. At the time of organ explantation, hemodynamic data were available from all patients. RESULTS: Early mortality in this group was 11%; cumulative survival after 5 years was 74%. CONCLUSIONS: Based on our limited experience, cardiac allografts from donors exposed to different kinds of poisons can be transplanted in selected cases. If the donor organ is not hemodynamically compromised, showing regular filling pressures on low or mild inotropic support just before explantation, and if there are no electrocardiographic changes in combination with elevation of the transaminases, cardiac allograft transplantation seems to be a safe and life-saving procedure.

Extended donor criteria: hemodynamic follow-up of heart transplant recipients receiving a cardiac allograft from donors > or = 60 years of age.

BACKGROUND: Heart transplantation (HT) has become a therapeutic option for patients suffering from endstage heart failure. The increasing demand for cardiac allografts has led to a shift toward extended donor criteria. In a retrospective analysis of 859 HT recipients, we report on the hemodynamic outcome of 19 HT patients who received cardiac allografts from donors > or =60 years of age. METHODS: From March 1989 to December 1997, we performed 883 orthotopic HT in 74 children and 809 adults at our transplant center. Within this period, 19 patients (17 women and 2 men) received cardiac allografts from donors > or =60 years of age. Recipient age ranged from 57 to 78 years (mean, 65+/-5 years). RESULTS: HT could be performed successfully in 19 cases. The early mortality rate was 16% (n=3). The late mortality rate was 37% (n=7). All long-term survivors are stable at New York Heart Association classification II (New York Heart Association Class II = resting hemodynamics: cardiac output normal; left ventricular end diastolic filling pressure elevated; clinically not compromised during mild to moderate workout). Although only 19 patients were retrospectively evaluated, there was a statistically significant (P<0.05) difference in survival among patients who received organs from male (11 vs. 8*) compared with female (8 vs. 2*) (*=death) donors. CONCLUSION: In our experience, it is possible to increase the cardiac donor pool by accepting allografts from donors, preferably female, > or =60 years of age in selected cases without a coronary angiogram, if hemodynamic parameters are in a normal range on mild-to-moderate inotropic support. We do not recommend cardiac allografts from donors > or =60 if there are signs of coronary insufficiency in the electrocardiogram, if left ventricle filling pressures are above normal on mild-to-moderate inotropic support and optimum hemodynamic management, or if there are signs of segmental dysfunction or mitral insufficiency >I in the echocardiogram.

Mechanical circulatory support after orthotopic heart transplantation.

Frequently the only therapy for primary graft- and right heart failure, as well as low output syndrome from acute of chronic rejection, is implantation of a mechanical circulatory support system, until recompensation or retransplantation. At our institution, mechanical assist devices were implanted in 25 heart recipients for a cute rejection (n=9), primary graft failure (n=7), acute right heart failure (n=7), and chronic rejection with low output syndrome (n=2). Patients (pts) with primary graft failure (n=3) received an intraaortic balloon pump (IABP), one pt an IABP plus Abiomed-System for left ventricular support, one pt the Thoratec-System for biventricular support. Patients with right heart failure (RHF) received the Biomedicus centrifugal pump for right ventricular support. Nine pts suffered from acute rejection. Six pts received an IABP, one the Biomedicus as femoro-femoral bypass, one the Abiomed-System for biventricular support, two the Thoratec-System for biventricular support and two within this group switched from the Biomedicus pump to the Thoratec-System for biventricular support. Patients with chronic graft failure (n=2) received the Novacor-System (LVAD) for left ventricular support, one received a Tojobo-System and an oxygenator for biventricular support post coronary artery bypass surgery. Support time ranged from 0.5-h to 73 days. Five pts were weaned. Two (8%) of 25 pts were retransplanted, 18 (72%) died in spite of mechanical support from multiple organ failure. The use of a mechanical assist device after heart transplantation is encouraging only in the case of early right heart failure, as well as primary and chronic graft failure. In view of the poor results, the use of mechanical assist devices should not be recommended in the case of heart failure caused by acute rejection.

Extended donor criteria: use of cardiac allografts after carbon monoxide poisoning.

BACKGROUND: An increasing demand for cardiac allografts for the treatment of end-stage cardiac failure has led to a shift in the traditional views about donor criteria. The use of allografts exposed to high concentrations of carbon monoxide is still under discussion. The current literature on this topic is contradictory. We describe our experience with orthotopic cardiac transplantation, using cardiac allografts after carbon monoxide poisoning. METHODS: Between March 13, 1989 and August 1, 1996, 770 orthotopic heart transplantations were performed in our center. Within this period, we accepted five cardiac allografts from brain-dead, carbon monoxide-poisoned donors. Donor history showed carbon monoxide intoxication in all cases. At the time of organ explantation, donor hemodynamic parameters were feeble in all patients. RESULTS: The postoperative course was uneventful in three of the five recipients. The overall 3-year survival rate in this small group is 40%. Induction therapy or rescue therapy with mono/polyclonal antibodies was not necessary. Myocardial right-ventricular biopsies did not show any specific signs of carbon monoxide poisoning. CONCLUSIONS: In our opinion, cardiac allografts from donors exposed to carbon monoxide can be transplanted successfully in infants and adults, if there are no signs of severe hemodynamic dysfunction in the presence of a normal central venous pressure and low-dose support with catecholamines and there are no electrocardiographic changes in combination with elevated transaminase. With extended donor criteria, the hearts of carbon monoxide-poisoned victims could increase the number of suitable organs and lower the death rate of patients on the United Network for Organ Sharing and Eurotransplant International Foundation waiting lists.

Heart transplantation at the Heart Center North Rhine-Westphalia in Bad Oeynhausen -- 1995 report.

Since March 1989, 713 heart transplants were performed at our center, limited only by donor availability. The induction of immunosuppression was based on double-drug therapy (CsA + Aza) without the use of mono- or polyclonal antibodies. Whenever possible, maintenance immunosuppression was based on CsA and Aza without steroids. Monitoring in adult patients was based on endomyocardial biopsies only during the first 12 months. In the pediatric patient group, only noninvasive diagnostic procedures were performed. The current 1- and 5-year survival rates for heart transplant patients are 80% and 75%, respectively.

Heart transplantation at the Heart Center North Rhine-Westphalia.

Since 1989, 427 heart transplants were performed at our center, limited only by donor availability, not by moderating donor criteria. Therefore, an increasing number of possible recipients was bridged with mechanical circulatory support systems. Immunosuppression was based on double-drug therapy (CsA, Aza) without steroid maintenance if possible and without mono- or polyclonal antibody prophylaxis. Monitoring adult transplant patients was based on endomyocardial biopsies only during the first 12 months posttransplant. In the pediatric group, only noninvasive diagnostic procedures were performed. Our present 1- and 3-year survival rates for heart transplant patients are 85% and 78%, respectively. We believe that only centers performing approximately 1,000 routine open-heart surgery procedures per year should be allowed to perform heart transplantation, with a minimum of 25 procedures per year (5). Our goal is to start our heart-lung and lung transplant programs in the near future. Our research interests are mainly in the field of postoperative monitoring, induction of immune tolerance, and in establishing a method to determine an individual immunosuppression protocol for each patient (6).