LEA29Y expression in transgenic neonatal porcine islet-like cluster promotes long-lasting xenograft survival in humanized mice without immunosuppressive therapy.

Genetically engineered pigs are a promising source for islet cell transplantation in type 1 diabetes, but the strong human anti-pig immune response prevents its successful clinical application. Here we studied the efficacy of neonatal porcine islet-like cell clusters (NPICCs) overexpressing LEA29Y, a high-affinity variant of the T cell co-stimulation inhibitor CTLA-4Ig, to engraft and restore normoglycemia after transplantation into streptozotocin-diabetic NOD-SCID IL2rγ-/- (NSG) mice stably reconstituted with a human immune system. Transplantation of INSLEA29Y expressing NPICCs resulted in development of normal glucose tolerance (70.4%) and long-term maintenance of normoglycemia without administration of immunosuppressive drugs. All animals transplanted with wild-type NPICCs remained diabetic. Immunohistological examinations revealed a strong peri- and intragraft infiltration of wild-type NPICCs with human CD45+ immune cells consisting of predominantly CD4+ and CD8+ lymphocytes and some CD68+ macrophages and FoxP3+ regulatory T cells. Significantly less infiltrating lymphocytes and only few macrophages were observed in animals transplanted with INSLEA29Y transgenic NPICCs. This is the first study providing evidence that beta cell-specific LEA29Y expression is effective for NPICC engraftment in the presence of a humanized immune system and it has a long-lasting protective effect on inhibition of human anti-pig xenoimmunity. Our findings may have important implications for the development of a low-toxic protocol for porcine islet transplantation in patients with type 1 diabetes.

Postoperative Heparin-Mediated Extracorporeal Low-Density Lipoprotein Fibrinogen Precipitation Aphaeresis Prevents Early Graft Occlusion after Coronary Artery Bypass Grafting.

Background Early graft occlusion due to thromboembolic events is a well-known complication after coronary artery bypass grafting (CABG). Fibrinogen, the coagulation factor I, is a glycoprotein that is transformed by thrombin into fibrin. It plays a major role in thrombus formation and is highly elevated after CABG. Our aim was to determine if postoperative lowering of fibrinogen levels by H.E.L.P. (heparin-mediated extracorporeal low-density lipoprotein [LDL] fibrinogen precipitation) aphaeresis could reduce the rate of early graft occlusion in patients with hypercholesterolemia undergoing CABG. Methods Between December 2004 and September 2009, 36 male patients with hypercholesterolemia (mean LDL cholesterol 128 ± 12 mg/dL), mean age 58 ± 9 years, underwent CABG. Mean preoperative fibrinogen level was 387 ± 17 mg/dL. H.E.L.P. aphaeresis was postoperatively performed when fibrinogen levels exceeded 350 mg/dL on day 1 and 250 mg/dL every consecutive day up to day 8. Pre- and postaphaeresis blood samples were obtained and plasma fibrinogen level reduction was calculated. Early graft occlusion was evaluated by means of coronary angiography or multislice computed tomography before discharge. Results A total of 128 distal anastomoses were performed in 36 patients (mean 3.6/patient). Postoperatively, 191 H.E.L.P. aphaeresis sessions were performed (mean 5.3/patient). Fibrinogen levels were lowered from 391 ± 10 mg/dL (preaphaeresis) to 171 ± 5 mg/dL (postaphaeresis; p < 0.001). Coronary angiography (multislice computed tomography in 7 patients) revealed graft patency in 125 of 128 grafts (98% patency) with three occluded venous grafts to target vessels of 1.5 mm. H.E.L.P. aphaeresis-related complications were limited to hypotensive episodes in two patients and bacteremia in one patient. Conclusions H.E.L.P. apheresis offers an easy, save, and efficient method to decrease fibrinogen postoperatively in patients having CABG. Showing excellent graft patency rates in comparison to the literature, this method is a promising tool to reduce early graft occlusion after CABG.

A single German center experience with intermittent inotropes for patients on the high-urgent heart transplant waiting list.

AIM: Currently, more than 900 patients with end-stage heart failure are listed for heart transplantation in Germany. All patients on the Eurotransplant high-urgent status (HU) have to be treated in intensive care units and have to be relisted every 8 weeks. Long-term continuous inotropes are associated with tachyphylaxia, arrhythmias and even increased mortality. In this retrospective analysis, we report our single center experience with HU patients treated with intermittent inotropes as a bridging therapy. METHODS AND RESULTS: 117 consecutive adult HU candidates were treated at our intensive care heart failure unit between 2008 and 2013, of whom 14 patients (12 %) were stabilized and delisted during follow-up. In the remaining 103 patients (age 42 ± 15 years), different inotropes (dobutamine, milrinone, adrenaline, noradrenaline, levosimendan) were administered based on the patient's specific characteristics. After initial recompensation, patients were weaned from inotropes as soon as possible. Thereafter, intermittent inotropes (over 3-4 days) were given as a predefined weekly (until 2011) or 8 weekly regimen (from 2011 to 2013). In 57 % of these patients, additional regimen-independent inotropic support was necessary due to hemodynamic instabilities. Fourteen patients (14 %) needed a left- or biventricular assist device; 14 patients (14 %) died while waiting and 87 (84 %) received heart transplants after 87 ± 91 days. Cumulative 3 and 12 months survival of all 103 patients was 75 and 67 %, respectively. CONCLUSION: Intermittent inotropes in HU patients are an adequate strategy as a bridge to transplant; the necessity for assist devices was low. These data provide the basis for a prospective multicenter trial of intermittent inotropes in patients on the HU waiting list.

Xenotransplantation of porcine islet cells as a potential option for the treatment of type 1 diabetes in the future.

Solid organ and cell transplantation, including pancreatic islets constitute the treatment of choice for chronic terminal diseases. However, the clinical use of allogeneic transplantation is limited by the growing shortage of human organs. This has prompted us to initiate a unique multi-center and multi-team effort to promote translational research in xenotransplantation to bring xenotransplantation to the clinical setting. Supported by the German Research Foundation, an interdisciplinary group of surgeons, internal medicine doctors, diabetologists, material sciences experts, immunologists, cell biologists, virologists, veterinarians, and geneticists have established a collaborative research center (CRC) focusing on the biology of xenogeneic cell, tissue, and organ transplantation. A major strength of this consortium is the inclusion of members of the regulatory bodies, including the Paul-Ehrlich Institute (PEI), infection specialists from the Robert Koch Institute and PEI, veterinarians from the German Primate Center, and representatives of influential ethical and religious institutions. A major goal of this consortium is to promote islet xenotransplantation, based on the extensive expertise and experience of the existing clinical islet transplantation program. Besides comprehensive approaches to understand and prevent inflammation-mediated islet xenotransplant dysfunction [immediate blood-mediated inflammatory reaction (IBMIR)], we also take advantage of the availability of and experience with islet macroencapsulation, with the goal to improve graft survival and function. This consortium harbors a unique group of scientists with complementary expertise under a cohesive program aiming at developing new therapeutic approaches for islet replacement and solid organ xenotransplantation.

Levosimendan for primary graft failure after heart transplantation: a 3-year follow-up.

BACKGROUND: Primary graft failure (PGF) is a severe complication responsible for 42% of the in-hospital mortality after heart transplantation. It has been postulated that once 30-day survival is achieved, patients with PGF have no increased risk of death. Levosimendan increases the 30-day survival among patients with PGF. Herein we have reported a 3-year follow-up at a single center of a patient cohort including PGF cases treated with levosimendan. METHODS: From September 2005 to December 2006 53 patients underwent heart transplantation at our institution, including 12 patients (22.6%) who presented with PGF and were treated with levosimendan using a 24-hour continuous infusion (0.10 µg/kg/min). Risk factors for 1-year and three-year mortality were analyzed using 30-day as well as 1 and 3-year survivals comparing patients with versus without PGF (n = 41). RESULTS: There were no significant differences in donor age, weight, height, and serum sodium between the groups. However, the ischemia time (259 ± 53 vs 227 ± 50 min; P = .06) and recipient age (51.6 ± 15 vs 41.5 ± 21 years; P = .07) were greater among the PGF patients. The 30-day survival rate was 92% in both groups. After 1 and 3 years, the survival rate was significantly lower among the PGF cohort (50% vs 80.6% and 41.7% vs 80.6%; P < .05) with 86.5% of PGF patients succunding due to non cardiac reasons, predominantly infections. CONCLUSIONS: Although treatment of PGF with levosimendan increased the 30-day survival, the 1 year and 3-year rates were reduced among this cohort of patients. PGF was associated with poor long-term outcomes, which may be a consequence of systemic malperfusion during the stage of cardiac low-output after transplantation.

Genetic polymorphisms of TP53 and FAS promoter modulate the progression of coronary artery disease after coronary artery bypass grafting: a gender-specific view.

INTRODUCTION: Progression of coronary artery disease (CAD) after primary coronary artery bypass grafting (CABG) is frequent and may lead to recurrent symptoms. Various data indicate that apoptosis is the main event occurring during development and progression of atherosclerotic plaque. Plaque vascular smooth muscle cells (VSMCs) are more sensitive than regular VSMCs to TP53-mediated apoptosis. METHODS: We investigated EDTA blood of 192 patients (18% female, age 60.9 ± 7.4 years) who had primary CABG more than 5 years ago. CAD progression was defined as clinical endpoints: re-operation (n = 88; 46%), catheter re-intervention (n = 58; 30%), or angina at follow-up (n = 89; 46%). Apoptotic gene polymorphisms (Toll-like receptor 2 A753G, FAS ligand C-844T, FAS promoter G-670A, TP53 Arg72Pro, and CD14 C-260T) were investigated by PCR-RFLP and compared to healthy controls (n = 200, 24% female, age 63.4 ± 5.4). Gender-specific analysis was carried out. RESULTS: Heterozygous, homozygous and wild-type expression of all five genetic polymorphisms showed almost identical distribution between patients with CAD and healthy controls. Looking at clinical endpoints, with GG expression of Toll-like receptor 2 polymorphism and GG expression of FAS promoter polymorphism, results showed a relative increased risk (p = 0.09) for recurrent symptoms and re-intervention. Patients with FAS promoter polymorphism with AA expression had an increased risk of suffering from recurrent symptoms (n = 28, p = 0.04). We found that patients with homozygous expression of TP53 polymorphisms (n = 3, all male) were prone to needing re-intervention after prior CABG (p = 0.03), but not re-operation. Over a period up to 15 years, the re-intervention rate was significantly different in homozygous genotypes of FAS LG, FAS promoter and TP53. CONCLUSIONS: Patients presenting with polymorphisms of FAS LG, FAS promoter and TP53 have an increased risk of CAD progression, as they have a higher rate of re-interventions.

Early prediction of cardiac allograft vasculopathy and heart transplant failure.

Early risk-prediction is essential to prevent cardiac allograft vasculopathy (CAV) and graft failure in heart transplant patients. We developed multivariate models to identify patients likely to experience CAV, severe CAV, and failure due to CAV, at 1, 5 and 10 years. A cohort of 172 patients was followed prospectively for 6.7 ± 3.9 years. Logistic regression models were developed and cross-validated using bootstrap resampling. Predictive markers of atherothrombosis (myocardial fibrin deposition, and loss of vascular antithrombin and tissue plasminogen activator) and arterial endothelial activation (intercellular adhesion molecule-1 expression) were measured in serial biopsies obtained within 3 months posttransplant. Most markers were univariately associated with outcome. Multivariate models showed that loss of tissue plasminogen activator was the dominant and, in most cases, only predictor of long-term CAV (p < 0.001), severe CAV (p < 0.001), and graft failure due to CAV (p < 0.001). The models discriminated patients having adverse outcomes, had particularly high negative predictive values (graft failure due to CAV: 99%, 99% and 95% at 1, 5 and 10 years) and predicted event incidence and time to event. Early absence of atherothrombotic risk identifies a patient subgroup that rarely develops CAV or graft failure, implying that this low-risk subgroup could possibly be followed with fewer invasive procedures.

Influence of polyclonal antithymocyte globulins on the expression of adhesion molecules of isolated human umbilical vein endothelial cells.

OBJECTIVES: Polyclonal antithymocyte globulins (ATGs) are immunosuppressive agents applied for the treatment and prevention of organ rejection after transplantation. ATGs induce complement-mediated cell death in T lymphocytes and decrease leukocyte adhesion. However, little is known about the effects of ATGs on endothelial cells (EC). Our aim was to study the influence of ATGs upon the expression of adhesion molecules on human umbilical vein endothelial cells (HUVECs) after stimulation with tumor necrosis factor (TNF)-alpha. MATERIAL AND METHODS: HUVECs obtained from umbilical cords were incubated with ATGs before and after 6-hour stimulation with TNF-alpha. The group incubated without ATG served as the controls. Another group was not stimulated with TNF-alpha. By flow cytometry, we analyzed the expression of several adhesion molecules: intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM), platelet EC adhesion molecule (PECAM), and CD62E. Statistical analysis used analysis of variance. RESULTS: After TNF-alpha stimulation, the EC surface expression of ICAM-1 and CD62E was reduced, although not significantly, in treated as compared with untreated cells. The expression of ICAM-1 and CD62E was similar in the unstimulated groups. The expression of VCAM, PECAM, CD55, and CD58 was not modified by ATG treatment. CONCLUSION: Our results demonstrated that ATGs insignificantly reduced the expression of adhesion molecules in HUVECs. The effect of ATGs on stimulated HUVECs remains unclear, probably due to the lack of effector cells.

Clinical heart transplantation with extended preservation time (>5 hours): experience with University of Wisconsin solution.

BACKGROUND: Use of University of Wisconsin solution has been suggested for extended organ preservation >4 hours in experimental cardiac transplantation, but few data have been reported from clinical use. This study investigated the impact of preservation with UW solution after prolonged ischemic times on myocardial damage and outcomes after heart transplantation. MATERIALS AND METHODS: Between 1994 and 2006, 34 orthotopic heart transplantations were performed at our institution with cold ischemic times of >or=300 minutes (mean, 325.1 +/- 21.3). Donor organs were perfused with and stored in 1000 mL of University of Wisconsin solution. No significant differences were observed with regard to age, gender, diagnosis, donor inotropic support, and donor-recipient weight ratio when compared with recipients undergoing an ischemic time <300 minutes. RESULTS: After a mean follow-up of 47.6 months (range, 1 day to 147.1 months), Kaplan-Meier survival analysis revealed survivals of 91.0% at 3 months, and 82.9% for the entire observation period. The time required to wean from bypass (mean, 78.1 minutes) was equal when compared with that of recipients experiencing grafts undergoing an ischemic time of <300 minutes, but there was a significantly greater average need for inotropic support over the first 48 posttransplant hours. Neither hospital stay in the ICU (mean, 13.0 days; range, 1-55 days) nor the incidence of acute graft failure or survival was different. CONCLUSION: We conclude that heart preservation with UW limited ischemic damage from prolonged storage and improved myocardial function in the early posttransplant period, thus allowing transplantation of organs with ischemic times >300 minutes.

Antithymocyte globulins bind to human umbilical vein endothelial cells.

OBJECTIVE: Polyclonal antithymocyte globulins (ATGs) are immunosuppressive agents used for the treatment of organ rejection after transplantation. ATGs induce complement-mediated cell death of T lymphocytes and may decrease leukocyte adhesion. However, little is known about their effects on endothelial cells (ECs). Our aim was to study whether they bind to human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: HUVECs obtained from umbilical cords were cultured and incubated with ATGs. A group incubated without ATG served as controls. All groups were coincubated with an anti-rabbit-IgG. Binding of ATGs to HUVECs was investigated by means of flow cytometry. Statistical analysis was performed using one-way analysis of variance (ANOVA). RESULTS: ATGs were bound to HUVECs with or without prior stimulation by tumor necrosis factor-alpha (TNF-alpha). Binding of ATGs to HUVECs was >99% in all treated groups. The mean intensity of fluorescence was constant in the ATG-treated groups. CONCLUSIONS: Our results demonstrated that ATGs bind to HUVECs before and after stimulation with TNF-alpha. Binding of ATGs to HUVECs suggests an independent endothelial mechanism of ATG action.

Multidrug-resistant gram-positive infections in patients with ventricular assist devices: the role of daptomycin.

OBJECTIVES: The rate of infection in patients who require ventricular assist devices (VADs) is estimated at more than 35%. Infections with multidrug-resistant (MDR) organisms in VAD recipients present a high mortality rate. Daptomycin (Cubicin, Novartis, Nuremberg, Germany), a new cyclic lipopeptide antibiotic, is useful for MDR gram-positive organisms. We report the successful use of daptomycin in patients presenting with MDR gram-positive infections after VAD implantation. METHODS: We retrospectively studied nine consecutive patients presenting with resistant gram-positive infections after VAD implantation treated with daptomycin. We analyzed type of VAD, type of infection, responsible microorganism, outcome, and adverse events. RESULTS: We studied nine patients (eight males, one female), of overall mean age of 51 +/- 8 years; 78% required a biventricular assist device or a left VAD (Berlin Heart, Berlin, Germany), 22% received other ventricular support. Sixty-six percent presented with catheter-related infections (CRIs). Therapy with daptomycin was empirically initiated in all cases. The initial dose was 6 mg/kg, continued at 4 mg/kg. The mean duration of therapy was 16 +/- 5 days. The reported pathogens were MRSA, 33%; E. faecium, 25%; methicillin-resistant staphylococcus epidermidis, 12.5%; methicillin-sensitive staphylococcus aureus, 12.5%; others, 17%. Successful outcomes were reported in seven subjects (78%), with two patients succumbing due to multiorgan failure related to their heart condition prior completing antibiotic therapy. No adverse events were reported. CONCLUSIONS: Among our VAD patients, daptomycin proved efficient as a therapy for CRI with bacteremia. However, controlled studies are necessary to evaluate this antibiotic in patients presenting with VAD and MDR bacteremia.

Proton pump inhibitors reduce mycophenolate exposure in heart transplant recipients-a prospective case-controlled study.

This prospective study investigates the impact of proton pump inhibitors (PPI) on mycophenolic acid (MPA) pharmacokinetics in heart transplant recipients receiving mycophenolate mofetil (MMF) and tacrolimus. MPA plasma concentrations at baseline (C(0 h)), 30 min (C(0.5 h)), 1(C(1 h)) and 2 h (C(2 h)) were obtained by high-performance liquid chromatography (HPLC) in 22 patients treated with pantoprazole 40 mg and MMF 2000 mg. Measurements were repeated 1 month after pantoprazole withdrawal. A four-point limited-sampling strategy was applied to calculate the MPA area under the curve (MPA-AUC). Predose MPA concentrations with PPI were 2.6 +/- 1.6 mg/L versus 3.4 +/- 2.7 mg/L without PPI (p = ns). Postdose MPA concentrations were lower with PPI at C(0.5 h) (8.3 +/- 5.7 mg/L vs. 18.3 +/- 11.3 mg/L, p = 0.001) and C(1 h) (10.0 +/- 5.6 mg/L vs. 15.8 +/- 8.4 mg/L, p = 0.004), without significant differences at C(2 h) (8.3 +/- 6.5 mg/L vs. 7.6 +/- 3.9 mg/L). The MPA-AUC was significantly lower with PPI medication (51.2 +/- 26.6 mg x h/L vs. 68.7 +/- 30.3 mg x h/L; p = 0.003). The maximum concentration of MPA (MPA-C(max)) was lower (12.2 +/- 7.5 mg/L vs. 20.6 +/- 9.3 mg/L; p = 0.001) and the time to reach MPA-C(max) (t(max)) was longer with PPI (60.0 +/- 27.8 min vs. 46.4 +/- 22.2 min; p = 0.05). This is the first study to document an important drug interaction between a widely used immunosuppressive agent and a class of drugs frequently used in transplant patients. This interaction results in a decreased MMF drug exposure which may lead to patients having a higher risk for acute rejection and transplant vasculopathy.

Interventional closure of two fistulas after aortic valve surgery.

INTRODUCTION: Paravalvular fistulas may complicate the clinical course after heart valve surgery. Medical treatment may be ineffective, repeated surgical revisions may be associated with increased morbidity and mortality. CASE REPORT: After valve sparing surgery in bicuspid aortic valve, a significant aorto-left atrial fistula was diagnosed in a 72-year-old patient causing heart failure and catecholamine-dependency. Due to the critical hemodynamic state, percutaneous closure was performed with an AGA Amplatzer duct occluder. Secondary to this closure, a second fistula between the aortic root and the right atrium appeared which was closed during the same procedure implanting a second duct occluder beneath the first device. CONCLUSION: Percutaneous closure of paravalvular fistulas is feasible and a safe method for the treatment of significant shunts after valve surgery. Even in multiple fistulas, the implantation of small devices allows for a focussed interventional closure of such leaks. This procedure should be considered for such defects as it represents a safe method for the causative treatment in paravalvular lesions after valve surgery especially in patients with critical hemodynamic conditions.

Design and fabrication of three-dimensional scaffolds for tissue engineering of human heart valves.

We developed a new fabrication technique for 3-dimensional scaffolds for tissue engineering of human heart valve tissue. A human aortic homograft was scanned with an X-ray computer tomograph. The data derived from the X-ray computed tomogram were processed by a computer-aided design program to reconstruct a human heart valve 3-dimensionally. Based on this stereolithographic model, a silicone valve model resembling a human aortic valve was generated. By taking advantage of the thermoplastic properties of polyglycolic acid as scaffold material, we molded a 3-dimensional scaffold for tissue engineering of human heart valves. The valve scaffold showed a deviation of only +/-3-4% in height, length and inner diameter compared with the homograft. The newly developed technique allows fabricating custom-made, patient-specific polymeric cardiovascular scaffolds for tissue engineering without requiring any suture materials.

Impact of polyclonal anti-thymocyte globulins on the expression of adhesion and inflammation molecules after ischemia-reperfusion injury.

BACKGROUND: Polyclonal anti-thymocyte globulins (ATGs) are immunosuppressive agents used for the treatment and prevention of acute organ rejection after transplantation. ATGs induce apoptosis and complement-mediated cell death in peripheral T-lymphocytes and have shown a reduction of leukocyte adhesion after ischemia-reperfusion (IRI). We analyzed the impact of different ATGs upon the expression of adhesion and inflammation molecules after IRI. MATERIALS AND METHODS: The major arteries and veins of the extremities of cynomolgus monkeys were surgically isolated and flushed with Ringer's lactate at 4 degrees C. After 60 min of ischemia the limbs were reperfused with matching human blood. ATGs were added to the blood 30 min prior to the reperfusion, forming four groups: Tecelac-ATG group (n=16), Fresenius(S)-ATG group (n=16), Thymoglobulin-ATG group (n=12) and a control group (n=16). Biopsies from muscular tissue were obtained after the experiments. The expression of adhesion (ICAM-1, VCAM, PECAM, CD11b, CD62E) and inflammation (IL-1, IL-6, TNF-alpha) molecules on endothelium, leukocytes, and reperfused tissue was analyzed by means of immunohistochemistry. RESULTS: The expression of the studied adhesion molecules (ICAM-1, VCAM, PECAM, CD11b, and CD62E) was significantly increased in the control group when compared with the treated groups. The expression of IL-1, IL-6, and TNF-alpha was reduced in the ATG-groups in comparison to the control group. DISCUSSION: Our results showed that ATGs caused a reduction of the expression of adhesion and inflammation molecules both in endothelium and reperfused tissue. The inhibition of the expression of molecules required for firm cellular adhesion, may contribute to decreasing cellular graft infiltration after post-ischemic reperfusion.

Primary graft failure and Ca2+ sensitizers after heart transplantation.

Primary organ failure after heart transplantation is a severe complication generally related to prolonged ischemia time, poor quality of the organ, or rejection. Ca(2+) sensitisers increase cardiac contractility without altering intracellular Ca(2+) levels. Our aim was to evaluate the influence of levosimendan in the therapy of primary failure after heart transplantation. Five patients presenting with reduced ejection fraction (EF<30%) and high dosed catecholamines after heart transplantation were treated with levosimendan (Simdax, Abbot GesmbH, Vienna, Austria) in a 24-hour continuous infusion (0.10 microg/kg*min) postoperatively. We assessed hemodynamic measurements including MAP, CVP, and PAP as well as heart function. Pharmacologic support with catecholamines could be halved at 24 hours and terminated in four of the patients 72 hours after levosimendan administration. Hemodynamics (MAP 70 +/- 11 vs 85 +/- 6 mm Hg; CI 2.5 +/- 0.4 vs 3.6 +/- 0.4 L/min/m(2)) and EF (28 +/- 10 vs 54 +/- 4%) improved at 48 hours after treatment. Acute graft failure after cardiac transplantation is associated with poor short- and long-term outcomes. Among our patients, levosimendan reduced the need for catecholamine support as well as improved ventricular performance.

Successful reimplantation of a passive-fixation ventricle lead perforating the chest wall.

Delayed perforation of a passive fixed pacemaker lead is a rare complication after pacemaker implantation and is associated with increased morbidity and mortality. We report the case of an 82-year-old patient who presented with a delayed perforation of the right heart wall, the pericardium, and the chest wall by a passive-fixation ventricular lead 14 months after pacemaker implantation. The lead was uneventfully extracted transvenously and repositioned in the right ventricle with good pacing and sensing.

[Assessment of aortic stenosis after aortic valve replacement: comparative evaluation of dual-source CT and echocardiography]. / Quantitative Evaluation der Aortenklappenöffnungsfläche mit der Dual-Source-CT und Korrelation mit der 2D-Echokardiografie: Initiale Ergebnisse.

PURPOSE: To prospectively evaluate whether planimetric measurements of aortic valve area (AVA) with dual-source computed tomography (DSCT) correlate with measurements obtained by echocardiography and to correlate the amount of calcification of the aortic valve with AVA in a group of patients after aortic valve replacement. MATERIALS AND METHOD: 23 patients underwent dual-source computed tomography (DSCT) of the heart (Somatom Definition, Siemens Medical Solutions, Forchheim, Germany), without heart rate control (heart rate 52-113 beats/minute). All patients had undergone aortic valve replacement (homografts, mean time after surgery: 7+/-3 years). The AVA of the transplanted aortic valve graft was measured planimetrically by means of DSCT and compared with echocardiography as a standard of reference, to exclude post-surgical restenosis of the valve. Maximum AVA in systole planimetrically measured with CT was compared with calculated AVA values determined with the continuity equation, using transvalvular pressure gradients. The amount of calcification of the aortic valve was quantified and correlated (Spearman's R) with the AVA. To assess intra- and inter-reader reproducibility, the DCST data was re-analyzed by two readers 4 weeks after the initial review. RESULTS: All DSCT datasets were of diagnostic image quality concerning valve depiction. The mean AVA as measured by DSCT was 2.7+/-0.9 cm (2) compared to 1.8+/-0.5 cm (2) by echocardiography (p<0.05). The planimetric evaluation of the CT data as compared to results of echocardiography showed a significant correlation of the results (Pearson's correlation coefficient R=0.78, p<0.001). Intra- and inter-reader reproducibility was good with intra-class correlation coefficients of 0.86 and 0.81, respectively (p<0.001). There was a significant negative correlation between the amount of aortic valve calcification and AVA as measured by echocardiography (R= -0.42; p<0.05) and as measured by DSCT (R= -0.67; p=0.001). CONCLUSION: First experience indicates that DSCT is able to assess aortic valve opening area with high image quality and good intra- and inter-reader reproducibility in subjects after aortic valve replacement. The negative correlation between AVA and the amount of aortic valve calcification suggests that calcification is a possible risk factor for restenosis in subjects with aortic valve replacement.