[Incidental finding of a cardiac paraganglioma]. / Zufallsbefund eines kardialen Paraganglioms.

Cardiac paragangliomas are extremely rare neoplasms with an incidence of 1% of all cardiac tumors and can be completely asymptomatic, therefore, diagnosis is difficult. This article reports the case of an 18-year-old man with a heart murmur detected during a routine physical examination. Echocardiography revealed a heart tumor measuring 7 cm in size in the right atrium. Due to the tumor size and the threat of tricuspid valve insufficiency, tumor resection was performed. The histopathological examination revealed a cardiac paraganglioma with positive reactions of the tumor cells for chromogranin A, synaptophysin and CD56. Differentiating a primary cardiac paraganglioma from other more common cardiac tumors and particularly from metastases of neuroendocrine neoplasms from other locations is essential not only for the further clinical treatment but also for the prognosis of the patient.

Evaluation of aortic cannula jet lesions in a porcine cardiopulmonary bypass (CPB) model.

In cardiosurgery patients atherosclerotic debris displaced from the cannulation site but also from the opposite aortic wall by the "sandblast-like" effect of the high-pressure jet emanating from the cannula is a potential source of intraoperative arterial embolization and consequently postoperative neurologic dysfunction. The present study examined the extent to which shear stress exerted on the intact aortic intima by an aortic cannula jet stream can cause endothelial lesions that promote thrombogenesis and consequently thrombembolism. A single-stream, straight-tip aortic cannula was used in a porcine cardiopulmonary bypass (CPB) model. Following a 120-minute CPB pump run, a 60-minute stabilization period was allowed before sacrificing the pigs (N.=40) for histological evaluation of the ascending aorta and the brain. Opposite the cannulation site endothelial lesions (diameter: 3.81±1.3 mm; depth: 0.017±0.003 mm) were present in 22.5% (9/40) of aortic specimens. Cerebral thrombembolic lesions were not found. The present study showed that single-stream, straight-tip aortic cannulas caused jet lesions of the formerly intact aortic endothelium opposite the cannulation site in 22.5% of cases in a porcine CPB model.

Considerations for patients awaiting heart transplantation.

The aim of this study is to provide a description of patients on the waiting list for heart transplants in Germany; the focus is on comparing the era after implementation of the new transplant law with the former era. This study used data from the Eurotransplant registry. The population consisted of all patients who registered for heart transplantation in Germany between January 1990 and May 2009. Patients were followed up to the earliest of the following events: heart transplantation, death, or end of the observation period. The actual mortality rates were calculated using a competing risk methodology. The proportion of patients on the waiting list aged 65 years or older has increased from 1.9 % in 1990 to 8.3 % in 1997, 7.8 % in 2000 and 12.6 % on December 31, 2008. The 1-year waiting list mortality rate, expressed as the proportion of patients who die within 1 year after being listed for heart transplantation decreased in the period 2001-2009 compared to the period 1991-2000. Patients registered in the period from 1991-2000 had a 25.9 % chance of dying prior to heart transplantation compared to 18.9 % for patients who were registered in the years 2001-2009. In the registration period 1981-1990, a transplant candidate had a 64.3 % chance of undergoing heart transplantation within the first year after being listed, while for patients who were registered in the period 2001-2009 this probability has been reduced to 40.2 %. Despite the fact that patient profiles have worsened and access to transplantation decreased, mortality rates of patients on the heart transplant waiting list have decreased. These data show that treatment of patients with advanced heart disease has improved in Germany.

The aging cardiomyocyte: a mini-review.

BACKGROUND: Aging per se is a risk factor for reduced cardiac function and heart diseases, even when adjusted for aging-associated cardiovascular risk factors. Accordingly, aging-related biochemical and cell-biological changes lead to pathophysiological conditions, especially reduced heart function and heart disease. OBJECTIVE: In this review, we summarize the changes that occur as the heart ages from youth to old age on the basis of the cardiac myocyte. Aging phenotypes and underlying mechanisms shall be discussed that affect cardiomyocyte repair, signaling, structure, and function. METHODS: Review of the literature. RESULTS: The following factors play vital roles in the aging of cardiomyocytes: oxidative stress, inflammation, cellular protection and repair, telomere integrity, survival and death, metabolism, post-translational modifications, and altered gene expression. Importantly, non-cardiomyocyte-based aging processes (vascular, fibroblast, extracellular matrix, etc.) in the heart will interfere with cardiomyocyte aging and cardiac function. CONCLUSION: Based on our analyses, we postulate that the physiological aging process of the heart and of the cardiomyocyte is primarily driven by intrinsic aging factors. However, extrinsic aging factors, e.g. smoking, also make an important contribution to pathologically accelerated aging of the heart.

Connective tissue changes in a mouse model of vein graft disease.

AIM: The extracellular matrix plays an important physiological role in the architecture of the vascular wall. In arterialized vein grafts severe early changes, such as thrombosis and neointimal hyperplasia occur. Paclitaxel is in clinical use as antiproliferative coating of coronary stents. We aimed to investigate the early connective tissue changes in arterialized vein grafts and the influence of perivascular paclitaxel treatment in an in vivo model. METHODS: C57 black mice underwent interposition of the vena cava into the carotid artery. Neointimal hyperplasia, thrombosis, acid mucopolysaccharides (Alcian), collagen fibers (trichrome Masson), elastic fibers, and apoptosis rate (TUNEL) were quantified in paclitaxel treated veins and controls. RESULTS: In both, controls and paclitaxel treated vein grafts acid mucopolysaccharides and elastic fibers were found predominantly in the neointima, whereas collagen fibers were found mainly in the media and adventitia. At 4 weeks postoperatively the neointimal thickness in controls was 52 (13-130) microm, whereas in 0.6 mg/mL l paclitaxel treated veins it was 103 (43-318) microm (P=0.094). At 8 weeks postoperatively paclitaxel treated veins showed a significantly increased neointimal thickness of 136 (87-199) microm compared with 79 (62-146) microm in controls (P=0.032). There was no difference in apoptosis rate between the two groups (P=NS). Even with the lowest concentration of 0.008 mg/mL paclitaxel veins showed a neointimal thickness of 67 (46-205) microm at 4 weeks postoperatively (P=NS vs controls). CONCLUSION: Early vein graft disease is characterised by an accumulation of acid mucopolysaccharides and elastic fibers in the thickened neointima. Paclitaxel treatment increases the neointimal hyperplasia in mouse vein grafts in vivo.

In vitro analysis of alpha-amanitin-resistant transcription from the rRNA, procyclic acidic repetitive protein, and variant surface glycoprotein gene promoters in Trypanosoma brucei.

In Trypanosoma brucei, transcription resistant to the mushroom toxin alpha-amanitin is not restricted to the rRNA genes (rDNA), as in higher eukaryotes, but extends to genes encoding the major cell surface proteins variant surface glycoprotein (VSG) and procyclin or procyclic acidic repetitive protein (PARP). Here, we report the development of a homologous cell extract from procyclic T. brucei cells in which rDNA and PARP A and VSG gene promoters drive efficient, accurate, and alpha-amanitin-resistant transcription. A comparative analysis revealed that transcription from the three promoters generally required identical reaction conditions for maximal efficiency. Nevertheless, PARP promoter transcription proved to be exceptional by its high efficiency, its lag phase, a high template DNA concentration optimum, and its tolerance to increasing concentrations of Mn(2+). Mutational analysis for both the PARP and rDNA promoters showed that the proximal and distal core elements were essential for efficient transcription in vitro. Deletion of the upstream control regions (UCRs), however, had a different effect. Whereas PARP UCR deletion reduced transcription efficiency almost 10-fold, deletion of the rDNA UCR had only a minor effect on transcription efficiency.

Do manual assisting maneuvers increase speed and technical performance in robotically sutured coronary bypass graft anastomoses?

BACKGROUND: Robotic endoscopic coronary artery bypass grafting procedures usually are performed as solo surgery operations. This study aimed to investigate whether manual assistance can reduce suturing times and anastomotic suturing problems in robotic coronary artery surgery. METHODS: In isolated pig hearts, the right coronary artery was excised from the epicardium as a pedicle. This pedicled vessel, which resembles the internal mammary artery, was sutured to the left anterior descending artery using the daVinci telemanipulation system. The anastomosis was performed in a running fashion using 7/0 Pronova. In group 1 (n = 20), the suture was performed by the console surgeon as a solo operation. In group 2 (n = 20), the anastomosis was assisted by a team member using an endo forceps. The operations were performed by five surgeons of different training levels. RESULTS: The overall anastomotic time was 24 +/- 15 min in group 1 and 22 +/- 12 min in group 2. The difference was not significant. The rate for anastomotic suturing problems (thread rupture, knot formation, sling formation, needle bending) was 8 in 20 (40%) in group 1 and 8 in 20 (40%) in group 2 (no difference). Anastomotic times and anastomotic suturing errors were dependent on surgeon experience. All anastomoses in both groups showed correct suture alignment and were probe patent. CONCLUSION: In a wet lab model of robotic coronary anastomoses, assisting maneuvers do not decrease suturing speed. Similar suturing quality can be achieved whether the suture is performed in a solo fashion or in an assisted manner.

Edwards Intuity Aortic Bioprosthesis in Patient with Bicuspid Aortic Valve.

Bicuspid aortic valve (BAV) is generally considered to be a contraindication to sutureless aortic valve replacement (AVR). Implantation of the Edwards Intuity aortic bioprosthesis is an innovative approach associated with superior hemodynamic performance, significantly reduced myocardial ischaemia and cardiopulmonary bypass times and proves to be suitable for type 1 and 2 of bicuspid aortic valves replacement. We report a case of successful AVR using a fast deployment bioprosthesis,the Edwards Intuity Valve System, in a 67-year-old woman with a bicuspid aortic valve and concomitant severe aortic stenosis.

First clinical experience with the DeBakey VAD continuous-axial-flow pump for bridge to transplantation.

BACKGROUND: A shortage of donor organs and increased numbers of deaths of patients on the waiting list for cardiac transplantation make mechanical circulatory support for a bridge to transplantation a standard clinical procedure. Continuous-flow rotary blood pumps offer exciting new perspectives. METHODS AND RESULTS: Two male patients (ages 44 and 65 years) suffering from end-stage left heart failure were implanted with a DeBakey VAD axial-flow pump for use as a bridge to transplant. In the initial postoperative period, the mean pump flow was 3.9+/-0.5 L/min, which equals a mean cardiac index (CI) of 2.3+/-0.2 L. min(-1). m(-2). In both patients, the early postoperative phase was characterized by a completely nonpulsatile flow profile. However, with the recovery of heart function 8 to 12 days after implantation, increasing pulse pressures became evident, and net flow rose to 4.5+/-0.6 L/min, causing an increase of mean CI up to 2.7+/-0.2 L. min(-1). m(-2). Patients were mobilized and put through regular physical training. Hemolysis stayed in the physiological range and increased only slightly from 2. 1+/-0.8 mg/dL before surgery to 3.3+/-1.8 mg/dL 6 weeks after implantation. CONCLUSIONS: The first clinical implants of the DeBakey VAD axial-flow pump have demonstrated the device to be a promising measure of bridge-to-transplant mechanical support.

Survival benefit of the implantable cardioverter-defibrillator in patients on the waiting list for cardiac transplantation.

BACKGROUND: The implantable cardioverter-defibrillator (ICD) effectively reduces sudden cardiac death in patients with severe LV dysfunction. Effect of ICD therapy on total mortality in patients on the waiting list for cardiac transplantation is still uncertain. METHODS AND RESULTS: We retrospectively analyzed 854 unselected consecutive patients (ICD therapy, n=102; 11.9%) on the waiting list for cardiac transplantation between January 1992 and March 2000. Actuarial 12-month total mortality rate on the waiting list was 24.2%; sudden cardiac death was the predominant mode of death (66.7% of total deaths). Kaplan-Meier analysis revealed improved survival for ICD (total mortality, 13.2%) compared with non-ICD (total mortality, 25.8%) patients (log rank, P=0.03). No event of sudden death occurred in ICD patients, whereas in non-ICD patients, 12-month sudden death rate was 20.1% (P=0.0001). Nonsudden death rates did not differ between ICD and non-ICD patients (P=0.16). A Cox proportional hazards model demonstrated that absence of an ICD was a powerful independent predictor of total mortality (P=0.02; relative risk, 2.22; 95% confidence interval, 1.16 to 4.17) and sudden cardiac death (P<0.0001; infinite relative risk) on the waiting list. CONCLUSIONS: ICD therapy, because it prevents sudden cardiac death, significantly improves survival on the waiting list for cardiac transplantation. The present study supports the use of ICDs as a bridge to transplantation in patients who are at risk of sudden cardiac death. Prospective randomized trials are needed to evaluate the potential benefit of prophylactic ICD therapy as a bridge to transplantation in all patients on cardiac transplant waiting lists.

Assessment of myocardial viability by dobutamine echocardiography, positron emission tomography and thallium-201 SPECT: correlation with histopathology in explanted hearts.

OBJECTIVES: We examined the relationship among viability assessment by dobutamine echocardiography (DE), positron emission tomography (PET) and thallium-201 single-photon emission computed tomography (TI-SPECT) to the degree of fibrosis. BACKGROUND: DE, PET and TI-SPECT have been shown to be sensitive in identifying viability of asynergic myocardium. However, PET and TI-SPECT indicated viability in a significant percentage of segments without dobutamine response or functional improvement after revascularization. METHODS: Twelve patients with coronary artery disease and severely reduced left ventricular function (EF 14.5+/-5.2%) were studied with DE prior to cardiac transplantation: 5 had additional PET and 7 had TI-SPECT studies. Results of the three techniques were compared to histologic findings of the explanted hearts. RESULTS: Segments with >75% viable myocytes by histology were determined to be viable in 78%, 89% and 87% by DE, PET and TI-SPECT; those with 50-75% viable myocytes in 71%, 50% and 87%, respectively. Segments with 25-50% viable myocytes showed response to dobutamine in only 15%, but were viable in 60% by PET and 82% by TI-SPECT. Segments with <25% viable myocytes responded to dobutamine in 19%; however, PET and TI-SPECT demonstrated viability in 33% and 38%, respectively. Discrepant segments without dobutamine response but viability by PET and SPECT had significantly more viable myocytes by pathology than did those classified in agreement to be nonviable but had significantly less viable myocytes than those classified in agreement to be viable (p < .001). CONCLUSIONS: These findings suggest that contractile reserve as evidenced by a positive dobutamine response requires at least 50% viable myocytes in a given segment whereas scintigraphic methods also identify segments with less viable myocytes. Thus, the methods may provide complementary information: Nuclear techniques appear to be highly sensitive for the detection of myocardial viability, and negative tests make it highly unlikely that a significant number of viable myocytes are present in a given segment. Conversely, dobutamine echo may be particularly useful for predicting recovery of systolic function after revascularization.

Factors associated with mortality and long time survival in patients undergoing modified Bentall operations.

AIM: We report our results on mortality, morbidity and long time events after composite graft replacement of the aortic root and ascending aorta/aortic arch and factors associated with them. METHODS: Seventy-four patients, aged 52 years (15-73) underwent modified ''button'' Bentall operation. The indication for operation was acute dissection in 29 (39%) patients, chronic dissection in 3 (4%), aortic regurgitation after previous replacement of the ascending aorta because of aortic dissection in 2 (3%) and non dissecting aneurysm in 40 (54%). Concommitant procedures were (partial) replacement of the aortic arch in 11 (15%) and coronary artery bypass grafting in 5 (7%). Six patients (8%) had undergone previous cardiac surgery. Mean follow up was for 49 +/- 46 months (maximum 198). RESULTS: Length of intensive care unit (ICU) stay was 3 days (1-72). Hospital mortality was 12%. Factors significantly associated with hospital mortality were: aortic dissection, cardiopulmonary bypass time, aortic cross clamp time, deep hypothermic circulatory arrest, low cardiac output syndrome, revision due to bleeding, renal failure requiring hemofiltration, multisystemic organ failure and sepsis. None of these factors was significantly associated with long term survival. Survival rates including hospital deaths were 86%, 84%, 75% and 75% after 1, 3, 5 and 7 years respectively. Pseudoaneurysm at the composite graft occurred in 3%, infection of the prosthesis in 1%. Neither valve thrombosis nor thromboembolic events occurred postoperatively. CONCLUSIONS: Modified Bentall operation is a demanding operation with acceptable hospital mortality. The long time survival rates are good and the big majority of patients is eventfree after operation.

Hybrid coronary artery revascularization: logistics and program development.

Planning hybrid coronary artery revascularization--a combination of cardiac surgery with percutaneous procedures--requires, at first sight, a very complex logistical setup. Technical and equipment related details should be defined as early as possible in order to have time for training of all OR personnel involved. The most challenging aspect in OR-located hybrid coronary revascularization remains a very close cooperation of cardiac surgeons and interventional cardiologists. This teamwork does include indication findings and subsequent referral of multivessel coronary artery disease patients to hybrid procedures, as well as high individual flexibility of interventionalists and surgeons. The major prerequisite for this cooperation is a mutual acceptance of different revascularization approaches and the intent to combine their most striking advantages. Intraoperative graft angiography during coronary artery bypass grafting (CABG) procedures is one important step toward simultaneous hybrid coronary revascularization procedures. We describe our experience with on table angiography using a mobile C-arm for intraoperative imaging. This fluoroscopy system can in selected cases be used for simultaneous hybrid procedures.

Ongoing procedure development in robotically assisted totally endoscopic coronary artery bypass grafting (TECAB).

BACKGROUND: Totally endoscopic coronary artery bypass grafting (TECAB) using robotics requires stepwise introduction into a heart surgery program. It is the aim of this study to evaluate the state of procedure development after continued application of telemanipulation techniques in the clinical setting. We also sought to assess perioperative and intermediate term clinical results after robotically assisted CABG. PATIENTS AND METHODS: From June 2001 to March 2005, robotically assisted CABG using the daVinci system was carried out in 107 patients with single and multi-vessel coronary artery disease. The following procedures were performed: robotically assisted endoscopic left internal mammary artery (LIMA) harvesting and completion of the procedure as conventional CABG, MIDCAB, or OPCAB (n = 22), robotically assisted suturing of LIMA-to-LAD anastomoses during conventional CABG (n = 28), TECAB on the arrested heart using remote access perfusion (n = 48), TECAB on the beating heart using an endostabilizer (n = 8), takedown of adhesions (TECAB intended) (n = 1). RESULTS: Hospital mortality was 0% and cumulative risk adjusted mortality reached 1.6 lives saved versus EuroSCORE predictions. Undesirable surgical events (USE) such as conversion, on table revision, or postoperative revision procedures occurred in 34 out of 107 (32%) patients. Median ventilation time and ICU stay, however, were 11(0-278) hours and 21(11-389) hours, respectively. Cumulative 3 years survival was 100% and freedom from angina at 3 years was 97%. CONCLUSIONS: We conclude that despite being surgically challenging robotically assisted coronary artery surgery can be implemented with acceptable safety. TECAB procedures have reached a reproducible state. Perioperative mortality after robotically assisted CABG may be lower than predicted. Intermediate term clinical results are very satisfactory.

Effect of mycophenolate mofetil therapy on inosine monophosphate dehydrogenase induction in red blood cells of heart transplant recipients.

BACKGROUND: Mycophenolic acid is reported to provide effective immunosuppression by inhibiting inosine monophosphate dehydrogenase. In an attempt to monitor the biological effects of long-term therapy with mycophenolate mofetil, we measured levels of guanosine 5' triphosphate and adenosine 5' triphosphate in red blood cells (RBCs) of patients after heart transplantations. METHODS: Fifty-two patients enrolled in the study were randomly assigned to one of two groups. Patients in the control group (n = 27) received cyclosporine A (INN, ciclosporin), azathioprine, and prednisone. Patients in the study group (n = 25) were switched from azathioprine to mycophenolate mofetil 3 months after the heart transplantation. Adenosine 5' triphosphate and guanosine 5' triphosphate levels were determined by means of HPLC. The activities of inosine monophosphate dehydrogenase and hypoxanthine-guanine phosphoribosyltransferase, which are responsible for guanine nucleotide formation, were measured in RBCs by radiochemical methods. RESULTS: Adenosine 5' triphosphate levels were unchanged in patients treated with mycophenolate mofetil, whereas those of the control group who received azathioprine (from 142 +/- 26 pmol/10(6) RBCs to 165 +/- 25 pmol/10(6) RBCs; P <.001) increased. As the length of mycophenolate mofetil therapy increased, patients in the study group showed significantly elevated guanosine 5' triphosphate levels (15.6 +/- 6.1 pmol/10(6) RBCs versus 6.6 +/- 2.1 pmol/10(6) RBCs; P <.001) and a 5-fold increase in inosine monophosphate dehydrogenase activity (108.6 +/- 13.3 pmol/mg of protein per hour versus 22.5 +/- 1.7 pmol/mg of protein per hour; P <.001) compared with the control group. In addition, a slight but significant enhancement of hypoxanthine-guanine phosphoribosyltransferase activity was seen in the mycophenolate mofetil group. CONCLUSIONS: Our studies have shown that long-term administration of mycophenolate mofetil is associated with increasing guanosine 5' triphosphate levels in RBCs as the result of an induction of inosine monophosphate dehydrogenase and hypoxanthine-guanine phosphoribosyltransferase activities in erythrocytes.

In-vitro competition analysis of procyclin gene and variant surface glycoprotein gene expression site transcription in Trypanosoma brucei.

In Trypanosoma brucei, alpha-amanitin-resistant transcription characteristic of RNA polymerase I is initiated at ribosomal RNA gene (RRNA), procyclin gene (GPEET or EP1), and variant surface glycoprotein gene expression site (VSG ES) promoters. The three promoter types do not share obvious sequence homologies, but contain a proximal domain I and a distal domain II within 80 bp upstream of the transcription initiation site. RRNA, GPEET and EP1, but not the VSG ES promoter, require additional upstream sequences for full activity. In the present study, we competed in-vitro transcription of circular template DNA with linear DNA fragments to identify promoter domains responsible for binding and sequestering essential trans-acting transcription factors. For the GPEET promoter, we found that domain III, located between positions -141 and -92, was most important for the DNA fragment to exert a transcription competition effect, whereas domain I, the only element absolutely required for transcription, was not. Moreover, insertions between promoter domains II and III reduced both transcription from the GPEET promoter and competition with the GPEET promoter fragment, suggesting that these two domains cooperate in the formation of a stable DNA-protein complex. Taken together, these results indicate a promoter structure very similar to that of the Saccharomyces cerevisiae RRNA promoter. In contrast, VSG ES promoter analysis showed that domains I and II are both necessary and sufficient to compete transcription. Despite this structural difference, our analysis provide evidence that GPEET and VSG ES promoters interact with a common factor that is also important for RRNA promoter transcription.

Demographic and perioperative factors associated with initial and prolonged sinus node dysfunction after orthotopic heart transplantation. The impact of ischemic time.

The etiology of sinus node (SN) dysfunction after orthotopic heart transplantation as assessed by the origin of rhythm, heart rate (HR), and, provided the origin of rhythm was sinus, by corrected sinus node recovery time (CSNRT) was studied in 50 patients. The possible influences on postoperative donor SN function of donor age, recipient age, underlying pretransplant heart disease, pretransplant amiodarone (AMIO) treatment, date of surgery, ischemic time, surgical technique of atrial incision, the use of different cardioplegic solutions during the study period, and rejection were evaluated. The results thus obtained indicate that SN dysfunction is common after cardiac transplantation and pinpoint to a different etiology of transient (restoration of normal SN function within 4 postoperative weeks) and persistent (SN function still impaired at 3 months) SN dysfunction. Of the several demographic and perioperative variables evaluated, only ischemic time had an influence on postoperative SN function in that ischemic times were significantly longer in patients with impaired SN function when compared with patients exhibiting normal SN function (148 +/- 39 min vs. 110.5 +/- 36 min, respectively, P = 0.001). Further stratification according to the duration of SN dysfunction revealed significantly longer ischemic times in patients with transiently impaired SN function only (156.3 +/- 35 min vs. 110.5 +/- 36 min, P = 0.0026). No relation to persistent SN dysfunction of ischemic time (130.5 +/- 36 min vs. 110.5 +/- 36 min, P = ns) or any other factor investigated was found.

The long-term effect of simultaneous heart and kidney transplantation on native renal function.

BACKGROUND: It is unclear whether patients with heart failure and renal insufficiency should receive a simultaneous heart and kidney transplant or whether a single heart transplantation is sufficient to restore native renal function. METHODS: We analyzed the renal plasma flow and glomerular filtration of the native and transplant kidneys in eight patients long term after simultaneous heart and kidney transplantation using a dynamic MAG3 radioisotope scan and serum creatinine determinations. All subjects had been hemodialysis dependent before transplantation. Seven patients suffered from an intrinsic renal disease that were diabetic nephropathy in three cases, small fibrotic kidneys of undetermined origin in two cases, one lupus nephritis, and cyclosporine nephrotoxicity in one patient who had a previous heart transplant. In one patient renal insufficiency was considered to be solely due to renal hypoperfusion because no intrinsic renal disease could be detected. RESULTS: All patients were on cyclosporine-based triple immunosuppression, transplanted for 4 to 10 years, exhibited cardiac ejection fractions of more than 50% and had normal serum creatinine values. Radioisotopic scan showed no function of the native kidneys in all seven patients with intrinsic renal disease but exhibited normal function of the native kidneys as well as the renal transplant in the patient without intrinsic kidney disease before transplantation. CONCLUSIONS: These data suggest that a simultaneous heart and kidney transplantation is necessary in patients with cardiomyopathy and renal insufficiency due to primary kidney disease, but not in those with hemodynamically mediated renal failure, even if an immunosuppressive regimen with calcineurin inhibitors is used.

The progression of mild acute cardiac rejection evaluated by risk factor analysis. The impact of maintenance steroids and serum creatinine.

The natural course of mild acute cardiac allograft rejection (MAR) under cyclosporine-based therapy is generally considered benign, and usually antirejection therapy is not instituted. The present study was undertaken to determine the frequency of and the risk factors for progression of MAR into a clinically significant (moderate or severe) rejection on subsequent endomyocardial biopsy (EMB). Among 167 cardiac recipients, transplanted from 3/1984 to 4/1990, MAR under cyclosporine-based therapy was diagnosed on 220 EMBs. Depending upon the outcome on the subsequent EMB, MAR was categorized as progressive or nonprogressive. This served as the dependent variable for a stepwise logistic regression analysis evaluating 11 covariates as potential risk factors: perioperative antibody prophylaxis (ATG vs. OKT3), maintenance therapy, underlying disease, HLA-mismatches for A- and B + DR-loci, serum creatinine (mg/dl) and cyclosporine HPLC blood level (ng/ml) at diagnosis of MAR and at subsequent biopsy, recipient age, donor age. 40 (18.2%) of 220 MARs became progressive as opposed to 37 (7.3%) of a control cohort of 507 negative EMBs (P less than 0.0001). Stepwise logistic regression yielded the type of maintenance therapy (P = 0.0019) and serum creatinine level at diagnosis of MAR (P = 0.0615) as independent predictors of progression of MAR. After adjustment for influence of maintenance therapy and serum creatinine none of the cyclosporine variables provided any additional information. MARs without maintenance steroids and low serum creatinine levels had the highest risk (37.2% observed incidence) to develop moderate or severe rejection on subsequent EMB. This analysis supports evidence that diagnosis of MAR on EMB is associated with a considerable high progression rate into clinically significant rejection when compared to negative EMBs. Progression particularly occurs in MAR under steroid-free maintenance therapy and suggests early augmentation of immunosuppression. In terms of progression of MAR serum creatinine values, obviously indicating cyclosporine nephrotoxicity, appear to reflect the extent of cyclosporine-mediated immunosuppressive activity more properly than parameters of its bioavailability by measuring cyclosporine HPLC blood levels.

Improved long-term results with thymoglobuline induction therapy after cardiac transplantation: a comparison of two different rabbit-antithymocyte globulines.

BACKGROUND: The aim of this retrospective single center analysis was to compare possible long-term benefits of two different rabbit-antithymocyte globuline (ATG) induction therapies after cardiac transplantation. PATIENTS AND METHODS: A total of 484 primary cardiac transplanted patients received induction therapy with two different rabbit-ATGs (thymoglobuline: n=342, ATG-fresenius: n=142). All patients received immunosuppressive maintenance therapy with cyclosporine, azathioprine, and prednisolone. Cardiac rejection was assessed by serial endomyocardial biopsies. Surveillance of graft arteriosclerosis was performed by angiograms 1, 3, and 5 years after transplantation. RESULTS: Five-year survival was significantly better in the thymoglobuline group (76 vs. 60%). Thymoglobuline patients had a lower rate of death from rejection (2.3 vs. 10%; P<0.01) and graft arteriosclerosis (0.88 vs. 5.6%; P<0.01). After 5 years, freedom from rejection was 72% in the thymoglobuline group compared to 42% in the ATG-fresenius group (P<0.01). Graft arteriosclerosis appeared in 14% of thymoglobuline patients and in 28% of ATG-fresenius patients (P<0.01). Viral infections occurred more often in thymoglobuline patients (53 vs. 39%, P<0.05) although there was no difference in appearance of cytomegalovirus disease (17 vs. 13%). Freedom from posttransplant malignant disease was comparable between the two groups. CONCLUSION: These results suggest that there are differences between rabbit ATG products. The superior prevention of rejection with thymoglobuline may be the reason for the lower rate of graft arteriosclerosis.