Calcineurin inhibitor-free immunosuppression using everolimus (Certican) after heart transplantation: 2 years' follow-up from the University Hospital Münster.

BACKGROUND: Everolimus is a proliferation-signal inhibitor which was introduced for heart transplant recipients in 2004. To date, there are only sparse data about long-term calcineurin inhibitor (CNI)-free immunosuppression using everolimus. METHODS: After heart transplantation, patients receiving everolimus were consecutively enrolled. Reasons for switching to everolimus were side effects of CNI immunosuppression, such as deterioration of kidney function and recurrent rejection episodes. All 60 patients underwent standardized switching protocols, 42 patients completed 24-month follow-up. Blood was sampled for lipid status, renal function, routine controls, and levels of immunosuppressive agents. On days 0, 14, and 28, and then every 3 months, echocardiography and physical examination were performed. RESULTS: After switching to everolimus, most patients recovered from the side effects. Renal function improved significantly after 24 months (creatinine, 2.1 ± 0.6 vs 1.8 ± 1 mg/dL; P < .001; creatinine clearance, 41.8 ± 22 vs 48.6 ± 21.8 mL/min; P < .001). Median blood pressure increased from 120.0/75.0 mm Hg at baseline to 123.8/80.0 mm Hg at month 24 (P values .008 and .003 for systolic and diastolic pressures, respectively). Tremor, peripheral edema, hirsutism, and gingival hyperplasia markedly improved. Levels of interleukin-6 were stable between baseline and 24-month levels. Temporary adverse events occurred in 8 patients [13.3%: interstitial pneumonia (n = 2), skin disorders (n = 2); reactivated hepatitis B (n = 1), and fever of unknown origin (n = 3)]. CONCLUSION: CNI-free immunosuppression using everolimus is safe, with excellent efficacy in maintenance of heart transplant recipients. Arterial hypertension and renal function significantly improved. CNI-induced side effects, such as tremor, peripheral edema, hirsutism, and gingival hyperplasia, markedly improved in most patients.

Effect of pulsatile and non-pulsatile left ventricular assist devices on the renin-angiotensin system in patients with end-stage heart failure.

INTRODUCTION: Left ventricular assist devices have been successfully used as a bridge to cardiac transplantation. Because many patients exhibit marked clinical improvement of their heart failure after LVAD implantation, we studied the physiological effect of pulsatile and non-pulsatile devices on the neurohormonal axis and exercise capacity. METHODS: We prospectively included 20 patients (17 men, 3 women) undergoing LVAD implantation between November 2001 and January 2004. Ten patients (1 woman and 9 men) were treated with the non-pulsatile INCOR-LVAD (Berlin Heart(c)) and ten patients received the pulsatile EXCOR LVAD (Berlin Heart(c)). Blood samples for plasma renin activity (PRA) were taken once a week over a period of ten weeks. All blood samples were collected in the morning before mobilization. Blood pressure, body weight, fluid intake and urine production were measured once a day. All patients received standard hospital diet with no limitation in fluid intake. RESULTS: Body weight remained constant in both groups throughout the ten weeks' examination, and fluid intake and urine production were balanced in all patients. Although there was no significant difference in mean blood pressure (INCOR: 70 +/- 10 mmHg; EXCOR: 73 +/- 10 mmHg), plasma renin activity was substantially elevated in patients with non-pulsatile left ventricular support (INCOR: 94.68 +/- 33.97 microU/ml; EXCOR: 17.06 +/- 15.94 microU/ml; P < 0.05). Furthermore plasma aldosterone levels were significantly higher in patients supported by non-pulsatile INCOR LVAD (INCOR: 73.4 +/- 9.6 microg/ml; EXCOR: 20.6 +/- 4.6 microg/ml; P < 0.05). CONCLUSIONS: Our data suggest that pulsatile as well as non-pulsatile left ventricular assist devices are equally able to treat chronic heart failure. However pulsatile devices seem to have a greater impact on reversing the changes in plasma renin activity and might thus offer a greater advantage when recovery of left ventricular function is expected.

German disease management guidelines: surgical therapies for chronic heart failure.

The German Disease Management Guideline "Chronic Heart Failure" intends to guide physicians working in the field of diagnosis and treatment of heart failure. The guideline provides a tool on the background of evidence based medicine. The following short review wants to give insights into the role of some surgical treatment options to improve heart failure, such as revascularization, ventricular reconstruction and aneurysmectomy, mitral valve reconstruction, ventricular assist devices and heart transplantation.

Limitations of high urgency listing--ventricular assist device support in a neonate for 452 days.

The Eurotransplant International Foundation in Leiden, the Netherlands, is responsible for mediation and allocation of organ donation procedures to its member countries Austria, Belgium, Croatia, Germany, Luxembourg, the Netherlands and Slovenia. To provide organs for the patients who require urgent transplantation, the "high urgent (HU)" status was introduced in 2001 in Germany . This new HU allocation system is applicable to neonates as well as adults. However, waiting times on HU status exceed several weeks to months. Therefore an increasing number of pediatric patients has to undergo implantation of a ventricular assist device (VAD). In the present report we discuss the current Eurotransplant heart allocation system for pediatric heart transplantation in the light of a neonate with 452 days on mechanical support. We compare the average waiting time of patients on HU status at our center and their outcome in 2007 and 2008 (Data obtained from Eurotransplant International Foundation). Waiting time on HU status in our center increased significantly from 2007 to 2008. Therefore more patients require VAD support as bridging to transplantation. The case of a neonate under long-term VAD support is an outstanding example of the negative effects of this development.

Heart transplantation for isolated noncompaction of the left ventricle in an infant.

Isolated noncompaction of the left ventricular myocardium is a rare cardiomyopathy typically showing a "spongy" myocardium on ultrasound. We report on the ultrasonic and pathomorphological characteristics of an infant who, at the age of 40 days, was treated by heart transplantation for isolated noncompaction. Noncompaction should be suspected in newborns with otherwise unexplained cardiomyopathy and a "spongy" left ventricle. However, ultrasonic and pathological findings may be much less pronounced at this age than later in life.

The excor device - revival of an old system with excellent results.

OBJECTIVE: We report on our experience with the BerlinHeart Excor system in adults and paediatric patients who underwent placement of the mechanical support device under emergency conditions and demonstrate the exceptional advantages and the considerable versatility of the system. METHODS: Since 2003, 29 consecutive patients (25 adults and 4 infants) with ages ranging from 10 months to 54 years underwent implantation of an Excor system. Main underlying heart diseases in adults were acute myocardial infarction (n = 9), dilative cardiomyopathy (n = 6), acute myocarditis (n = 6), whereas most of the children suffered from dilative cardiomyopathy. Ten patients had undergone implantation of an extracorporeal membrane oxygenation system. RESULTS: In 26 cases, a left ventricular assist device (LVAD) was implanted, while 3 patients had biventricular support. The support interval of all patients surviving the perioperative period lasted from 30 to 412 days, mean period of support until heart transplantation or explantation was 184 +/- 117 days. Severe complications were rare. CONCLUSION: The Excor paracorporeal mechanical support system is an excellent and highly versatile device for the support of patients of all ages and different types of underlying heart disease in the mid-term and long-term. The implant procedure and the perioperative management are simple, and complication rates are low.

Aminoterminal B-type pro-natriuretic peptide as a marker of recovery after high-risk coronary artery bypass grafting in patients with ischemic heart disease and severe impaired left ventricular function.

BACKGROUND: Aminoterminal B-type pro-natriuretic peptide (NT-proBNP) is a reliable indicator of heart failure severity. Levels of NT-proBNP are markedly increased in patients with coronary artery disease (CAD) and severely impaired left ventricular (LV) function. The aim of our study was to assess the impact of NT-proBNP levels after high-risk coronary artery bypass grafting (CABG) with regard to recovery potential. METHODS: Between 1998 and 2004, 121 patients with CAD and severely impaired LV function, who were undergoing CABG, were investigated. Their mean age was 64 +/- 11 years. All patients were in New York Heart Association (NYHA) Class III/IV status; LV ejection fraction (EF) was 20 +/- 6%. All survivors underwent follow-up (59 +/- 34 months) spiroergometric, electrocardiographic (ECG) and echocardiographic assessment and were tested for routine blood controls and NT-proBNP levels (Roche, Mannheim, Germany). RESULTS: The survival rate after 8 years was 70%. All survivors received follow-up assessment. Among survivors the median NT-proBNP level at follow-up was 896 (521 to 1,687) pg/ml. The maximum oxygen uptake was 14.6 +/- 4.9 ml/min/kg, and EF increased to 42% at follow-up among all survivors. On dichotomizing survivors into two groups with NT-proBNP levels above and below the median, the post-operative body mass index was significantly higher in the high NT-proBNP group (p = 0.036). EF (p = 0.028) and NYHA classification (p < 0.05) improved significantly in both groups, with a tendency toward higher EF in the low NT-proBNP group. CONCLUSIONS: Patients undergoing a high-risk CABG procedure have a survival rate comparable to heart transplantation patients and show a potential for clinical and myocardial recovery. NT-proBNP use a useful marker for recovery after a high-risk CABG procedure, with significant correlation with clinical parameters.

Posttraumatic stress disorder after implantation of a mechanical assist device followed by heart transplantation: evaluation of patients and partners.

AIM: We sought to investigate the prevalence of posttraumatic stress disorder, anxiety, and depression in patients and their partners after implantation of a mechanical assist device as a bridge to heart transplantation. METHODS: This was a retrospective assessment of 41 patients (age 46.3 +/- 12.0 years; male-female ratio, 38:3; time since transplantation, 55.3 +/- 34.2 months [range, 7-122 months) and 27 partners (male-female ratio 2:25) by standardized instruments (Impact of Event Scale, Hospital Anxiety and Depression Scale), in 2 University Heart Transplant Centers (Vienna, Austria, Munster, Germany). The duration of the support systems (MicroMed DeBakey-VAD in 17 patients, Novacor in 10, Thoratec in 8, TCI HeartMate in 5, and Berlin Heart Incor in 1 patient) ranged from 28 to 711 (176 +/- 146) days. RESULTS: None of the patients, but 23% of the partners (n = 6), met the criteria for posttraumatic stress disorder (Maercker cutoff >0). The Impact of Event Scale (IES) sum scales differed significantly between the 2 groups (21.2 +/- 15.1, mean +/- SD) for the patients versus 38.1 +/- 27.8 for the partners, respectively; P = .001). Two percent of the patients, but 19% of the partners, showed mild to moderate depression; 4% of patients, but 23% of their partners, reported mild to moderate anxiety. None of the results were significantly influenced by the time since transplantation, patient age, diagnoses, type of assist device, or indication for heart transplantation. CONCLUSIONS: Despite patients being much closer to a life threat, their partners experience significantly more psychologic distress even in the long run. Our findings highlight the need for attention to the supporting persons.

Cardiothoracic surgery after heart and heart-lung transplantation.

OBJECTIVE: We sought to examine our management and the outcomes of cardiothoracic procedures after heart and heart lung transplantation. METHODS: We performed a retrospective review of cardiothoracic surgical procedures carried out between 1990 and 2004 in patients who had previously undergone heart or heart-lung transplantation at our institution. RESULTS: Twenty-one out of 340 patients (6.2 %) were identified. Cardiothoracic surgery was performed 44.4 +/- 33 months (range 1 - 115 months) after transplantation. Predominant types of surgery were coronary artery bypass grafting due to allograft vasculopathy (n = 5), aortic surgery due to acute dissection (n = 3), biventricular assist device implantation due to acute rejection (n = 1), tricuspid valve repair (n = 1), multiple cardiac surgical procedures including coronary artery bypass grafting, retransplantation, and tricuspid valve replacement (n = 2), explantation of a functionless heterotopic transplanted heart (n = 1). Lung surgery was performed in six patients due to pneumonia (n = 2), primary lung carcinoma (n = 3), lung torsion following heart-lung transplantation (n = 1). All patients underwent either lobectomy or segmental lung resection. Single lung retransplantation (n = 2) after prior heart-lung transplantation due to bronchiolitis obliterans was performed. In one patient a pneumonectomy (n = 1) due to severe chronic rejection of the contralateral lung was performed. Six subsequent deaths after cardiothoracic procedures were recorded after 1, 4, 78, 163, 205, and 730 days, respectively. Causes of death were advanced carcinoma (n = 1), multi-organ failure due to sepsis (n = 2), sudden heart death (n = 2), and advanced heart failure (n = 1). Fifteen out of 21 patients having undergone cardiothoracic procedures (71.4 %) survived the observation period of 56.6 +/- 34 months (range 1 - 114). CONCLUSIONS: Reasons for cardiothoracic procedures after prior heart or heart-lung transplantation were allograft vasculopathy, aortic dissections years after transplantation, chronic rejection, and either lung infections or malignancies. Surgical repair can be performed with an acceptable operative risk and good long-term survival rates.

Neoplastic heart disease -- the Muenster experience with 108 patients.

BACKGROUND: Tumours of the heart are rare. Different histological subtypes are known. The most common tumour entity is benign cardiac myxoma. Malignant heart tumours are less common. Tumours originating in other organs such as the kidney may also affect the heart by tumour progression via the inferior caval vein. A large experience with surgical treatment of different types of heart tumours is presented. METHODS: Between January 1989 and April 2004, 108 patients with a heart tumour were included in a database. All patients underwent radical surgical resection, except for 2 patients who had malignant lymphoma of the heart. RESULTS: Histological findings included 78 myxomas (72.2 %), and 6 other benign cardiac tumours in 5.6 % of the patients. Primary malignant heart tumours were seen in 10 (9.2 %) and renal cell carcinoma with cardiac involvement in 6 (5.6 %) patients. Eight patients presented with tumour metastases inside the heart (7.4 %). Mean overall survival was 12.7 years for myxoma patients and 5.6 years for patients with other benign heart tumours. Patients with primary malignant heart tumours survived 5.5 years on average. CONCLUSIONS: Heart tumours are rare, but usually life-threatening. Radical surgical resection is the therapy of choice and may offer excellent long-term survival, even in cases with malignant heart tumours.

Psychological care of heart-transplanted children and their families.

Heart transplantation is not a unique event, neither from the medical point of view nor from the standpoint of psychosocial care. It is a process which begins during the evaluation for transplantation and continues up to re-integration of the patient into everyday life. It is obvious that during the entire time both the child suffering from heart disease and the family of the affected child have to deal with heavy emotional stresses and adjustments. For this reason transplantation centers are obliged by law to provide psychological care.

Radical resection of cardiac sarcoma.

We report on our experience with six patients with malignant sarcoma of the heart and show that long-term survival is possible after radical resection. At presentation, the 6 patients (3 male, 3 female) were 45.8 +/- 20 years old. Three patients are alive without evidence of metastases since 29.6 +/- 36.8 months, three patients died after 38 +/- 50.2 months due to distant metastases. Precise preoperative localization of the tumor by means of imaging techniques is very important. In some cases, radical surgery requires an ex situ procedure (autotransplantation). If necessary, the right heart can be resected almost completely, and reconstructed in the form of a Fontan-type circulation. A heart transplantation, as suggested by others, is not justified from our point of view, since prognosis is not better and donor organs are too rare. The results of radical resection are promising, but new concepts for treatment--in particular chemotherapy concepts--for these mostly middle-aged or young patients are required.

Ambulatory care of patients with left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVAD) have revolutionized the treatment of patients with acute and chronic heart failure as they provide a high quality of life. We report on our experience with patients receiving ambulatory care after LVAD implantation. METHODS AND RESULTS: Since July 1995, 46 patients with a mean age of 45+/-11 years underwent implantation of an electrically driven LVAD with portable controller and batteries. Sixteen (35%) patients bridged >30 days were treated in part on an outpatient basis. After LVAD implantation, they were treated in the hospital for 86+/-32 days (range 40 to 153 days). Afterward, they received ambulatory care for 74+/-76 days (range 2 to 301 days, total experience 1206 days). In 13 cases, the outpatient treatment was interrupted by 1.7+/-1.7 readmissions, for a total of 32+/-42 days (median 19 days). Reasons for readmission included systemic or drive line infections (incidence 0.0066 per outpatient day), suspected or true thromboembolic events (incidence 0.0066 per outpatient day), and suspected malfunction of the LVAD. One patient supported as alternative to transplantation died after cerebral bleeding after 244 days, 1 patient with a history of acute myocarditis had ventricular fibrillation during LVAD assist while being at home for 177 days and died in a low output state, 10 patients were given transplantation after a mean support interval of 206+/-88 days, and 4 patients currently await heart transplantation. CONCLUSIONS: Outpatient treatment after LVAD implantation is feasible, and severe complications are uncommon.

[Individual learning curves with reference to endonasal micro-endoscopic pan-sinus operation]. / Individuelle Lernkurven der endonasalen mikro-endoskopischen Pansinusoperation.

BACKGROUND: We examined how surgeons in training will develop into experienced surgeons in sinus surgery by analysing their individual learning curve. METHODS: In a retrospective study we evaluated complications in 818 surgical procedures (362 revisions = 44.3%) performed by four different surgeons. RESULTS: We found a dural lesion in six cases (0.75%), opening of the periosteum of the orbit in 30 cases (3.7%), and control of bleeding from the anterior ethmoidal artery in 36 cases (4.4%). No lesions of the internal carotid artery or lacrimal duct system occurred. The complications were not distributed equally. We observed a three-phase learning process which we describe using the example of a traffic light: red with a high risk of complications, yellow with a minor one, and green for the experienced surgeon. The first phase consists of the first 20 procedures, yellow from the 20th to the 100th, and green for procedures performed thereafter. CONCLUSIONS: Each inexperienced surgeon has to determine his position on the learning curve. He or she should be supervised accordingly.