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.

Sex mismatch in heart transplantation is associated with increased number of severe rejection episodes and shorter long-term survival.

BACKGROUND: Heart transplantation is the criterion standard for treating end-stage heart failure. Male sex of both the donor organ and the recipient is advantageous for survival, possibly owing to hemodynamic or immunologic reasons. The effect of sex mismatch on long-term survival in male heart transplant recipients is less known. PATIENTS AND METHODS: In this prospective single-center study, we reviewed follow-up data for 57 sex-mismatched and 179 sex-matched men who underwent orthotopic heart transplantation between 1990 and 2002. RESULTS: Median survival was significantly shorter in the sex-mismatched group (8.1 vs 12.9 years; P < .04). Subgroup analysis revealed that this was even more pronounced in male heart recipients with coronary artery disease (2.4 vs 12.9 years; P < .001). Female donor organs were significantly smaller (left ventricular end-diastolic diameter 49 vs 51 mm; P < .05), and recipients more often experienced clinically relevant episodes of cellular rejection during the first 3 months posttransplantation (International Society for Heart and Lung Transplantation grade 3, 5.6% vs 3.1%; P < .001). Global left ventricular function, and immunosuppressive and inflammatory parameters did not differ. CONCLUSION: In male orthotopic heart transplant recipients, sex mismatch is associated with adverse outcome owing to increased number and severity of episodes of graft rejection.

Implantation of a right heart assist device without a heart-lung machine in a patient with an acontractile right ventricle and HIT Type II.

A simple surgical technique to insert an RVAD without the use of a heart-lung machine and without full anticoagulation is described here.

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.

Clinical situations demanding weaning from long-term ventricular assist devices.

OBJECTIVE: Ventricular assist devices are increasingly used to treat patients with acute or chronic end-stage heart failure. We report on circumstances, exemplified on four cases, where a surprisingly favorable clinical course of the patients ultimately demanded early explantation of the device, which was not anticipated prior to its implantation. METHODS: The four patients were provided with implantable (Micromed BeBakey trade mark, Incor trade mark ) and external pneumatically driven (Thoratec trade mark, Excor trade mark ) devices under emergency conditions and were listed for heart transplantation. RESULTS: All four patients had an unexpected recovery of myocardial pump function. After careful diagnostic evaluation, all device components were completely removed without extracorporeal circulation. No stepwise weaning protocol was employed. CONCLUSIONS: Weaning patients from ventricular assist devices after recovery of myocardial pump function can become necessary. Diagnostic evaluation and the implementation of a weaning protocol is still a matter of debate, while complete surgical removal of all device components without extracorporeal circulation is possible with a low risk.

Successful long-term bridge to transplant in a 5-year-old boy with the EXCOR left ventricular assist device.

We report on a 5-year-old boy who presented with postcardiotomy failure after aortic valve replacement and had to undergo implantation of a Berlin Heart-Excor system since treatment with ECMO did not improve myocardial pump function. After a stormy postoperative course with delayed sternal closure after 9 days, the young boy finally recovered and could be fully mobilized. Until successful heart transplantation after a support interval of 77 days, he experienced no device-related infectious or thromboembolic complications.

First experience with rapamycin-based immunosuppression to improve kidney function after heart transplantation.

UNLABELLED: This study was designed to gain initial experience with rapamycin in thoracic organ transplant recipients with severely compromised kidney function, i.e. to see whether and how kidney function will improve with a rapamycin-based immunosuppressive protocol. METHODS: Twelve heart transplant patients were included into the study (serum creatinine > 2.5 mg/dL), with an average time after transplantation of more than 4 years. The calcineurin inhibitor (cyclosporine A = 9, tacrolimus = 3) was reduced by 50 %, and rapamycin added to reach a target level of 8 - 12 ng/dL. Azathioprine was halted, corticosteroid treatment remained unchanged. RESULTS: After implementing the rapamycin-based immunosuppression kidney function improved in all patients within one week. Serum creatinine dropped from 3.1 +/- 0.6 mg/dL to 2.7 +/- 0.5 mg/dL ( p = 0.0004), creatinine clearance increased from 30.4 +/- 11 mL/min to 40.8 +/- 10.5 mL/min ( p = 0.003). This improvement continued until 3 months after the conversion ( p = 0.032). Thereafter, no statistically significant changes were noted up to 6 months posttransplant ( p = 0.41). Serum cyclosporine levels dropped from 180 +/- 40 ng/mL to 132 +/- 46 ng/mL on average ( p = 0.002). Side-effects occurred in 4 patients and were all related to a rapamycin level exceeding 12 ng/mL. CONCLUSIONS: We conclude that transplant patients with impaired kidney function will have an immediate benefit from partially replacing calcineurin inhibitors by rapamycin.

Left ventricular assist stand-by for high-risk cardiac surgery.

BACKGROUND: Patients with severely impaired left-ventricular pump function who are eligible for heart transplantation increasingly undergo high-risk cardiac surgery due to the scarcity of donor organs. If these patients also qualify for long-term mechanical support, the latter can be used as back-up in case of postcardiotomy failure. METHODS: Since 1994, 36 patients (34 male, 2 female; mean age 51 +/- 7 years) underwent coronary bypass surgery/aneurysmectomy (n = 27), aortic valve replacement (n = 4), both (n = 1), or partial left ventriculectomy (n = 4) with a long-term mechanical assist device (Novacor, HeartMate, DeBakey) and were kept on stand-by with the device. Average left ventricular ejection fraction was 23 +/- 9 %, NYHA 2.9 +/- 0.5, and CCS 2.7 +/- 0.9. An intraaortic balloon pump was inserted prior to surgery in 13 patients. RESULTS: In 31 patients, high-risk surgery was performed, whereas 5 patients underwent immediate device placement as coronary revascularization was deemed impossible. 6 patients had postcardiotomy failure after coronary bypass surgery and were immediately provided with a long-term assist system. There were no significant differences in risk factors between the patient subsets. All conservatively operated patients survived and left the institution after 9.4 days and are currently at NYHA 1.5 +/- 0.5 or CCS 1.0 +/- 0, respectively. 6 of the 11 LVAD patients could be bridged to heart transplantation after 43 - 418 days, and 1 patient is still on support. CONCLUSION: High-risk conventional surgery with LVAD stand-by is feasible and seems to be a valuable alternative for heart-transplant candidates.

Accidental intoxication with methylene dianiline p,p'-diaminodiphenylmethane: acute liver damage after presumed ecstasy consumption.

BACKGROUND: MDA is the abbreviation for methylene dianiline (p,p' diaminodiphenylmethane; 4,4'-methylenedianiline; CAS 101-77-9); and for methylendioxyamphetamine (MDMA, N, alpha-dimethyl-1,3-benzodioxole-5-ethanamine; CAS 42542-10-9). While the former is used for the production of polyurethane foams, the latter is a psychometric drug, which is becoming increasingly popular in the techno scene. METHODS: We report six participants of a technoparty (1 female, 5 males, ages 17-25) who were admitted to the hospital with severe colicky abdominal pain and subsequently developed symptoms of hepatotoxicity. They had ingested an alcoholic beverage that had been spiked with a powdery substance they dubbed MDA. RESULTS: All patients showed similar clinical symptoms, with an identical time course. Acute jaundice developed within 2 days after ingestion. Enzymes indicating cholestasis increased steadily over 7 days and reached peak values of 800 U/L (AP) and 380 U/L (GGT), whereas transaminases remained moderately elevated. Between days 5 and 7, all patients became febrile for one day, their body temperatures rising up to 40 degrees C. There was no evidence for hemolysis or an infectious hepatitis. Toxicological analysis revealed the presence of p,p'-diaminodiphenylmethane (4,4'-methylenedianiline) at a concentration of 130 mg/L in one of two urine extracts examined. CONCLUSIONS: The analytical data indicate that the participants of the technoparty assumed the aniline-derivative, the cause of Epping Jaundice, was methylendioxyamphetamine because the same abbreviation, MDA, is used for both compounds. An overview of the acute liver toxicity of aniline derivatives is given and the possibility of amphetamine-induced liver damage is discussed.