Clinical, haemodynamic and echocardiographic features of early cardiac graft dysfunction.

Background: The main cause of early death after heart transplantation (HTx) is so-called early primary or secondary graft failure (GF). The risk of profound GF has not declined in the past decade, as the consequence of the liberalisation of donor acceptance criteria because of the scarcity of donors. It is therefore important to try to diagnose graft failure and recognise the mechanisms of early graft dysfunction.

Non-HLA antibodies targeting vascular receptors enhance alloimmune response and microvasculopathy after heart transplantation.

Background: Non-human leukocyte antigen antibodies (Abs) targeting vascular receptors are implicated in the pathogenesis of renal allograft vascular rejection and in progressive vasculopathy in patients with systemic sclerosis.

Methods: We prospectively tested in 30 heart transplant recipients the impact of Abs directed against endothelin-1 type A (ET(A)R) and angiotensin II type 1 receptors (AT(1)R, cell-enzyme-linked immunosorbent assay) at time of transplantation and during the first posttransplantation year on cellular and Ab-mediated rejection (immunohistochemistry, C3d, and immunoglobulins) and microvasculopathy in endomyocardial biopsy.

Results: Cellular rejection, Ab-mediated rejection, and microvasculopathy was found in 40% and 13%, 57% and 18%, and 37% and 40% of biopsies at 1 month and 1 year posttransplantation, respectively.

Invasive pressure monitoring saves from tuberculous meningitis with fulminant generalized brain edema.

We report a 57-year old female patient with a rapid and dramatic dynamic of whole brain edema caused by tuberculous meningitis. After initiation of tuberculostatic medication, general condition of the patient worsened and finally she was intubated due to a progredient loss of consciousness and respiratory insufficiency. Repeated cerebral computer tomography (CCT) revealed a global brain edema with slit ventricles and a dramatic progress of generalized brain swelling.

Everolimus prevents endomyocardial remodeling after heart transplantation.

Background: Endomyocardial remodeling is characterized by progressive fibrosis and scars and may develop after heart transplantation. The role of everolimus in preventing this process has not been evaluated as yet.

Methods: We prospectively studied 132 patients at baseline pretransplant and at 4 weeks, 1 year, and 3 years after heart transplantation.

Report from a consensus conference on antibody-mediated rejection in heart transplantation.

Background: The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation.

Methods: The conference included 83 participants (transplant cardiologists, surgeons, immunologists and pathologists) representing 67 heart transplant centers from North America, Europe, and Asia who all participated in smaller break-out sessions to discuss the various topics of AMR and attempt to achieve consensus.

International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.

The development of cardiac allograft vasculopathy remains the Achilles heel of cardiac transplantation. Unfortunately, the definitions of cardiac allograft vasculopathy are diverse, and there are no uniform international standards for the nomenclature of this entity. This consensus document, commissioned by the International Society of Heart and Lung Transplantation Board, is based on best evidence and clinical consensus derived from critical analysis of available information pertaining to angiography, intravascular ultrasound imaging, microvascular function, cardiac allograft histology, circulating immune markers, non-invasive imaging tests, and gene-based and protein-based biomarkers.

Angiographic assessment of cardiac allograft vasculopathy: results of a Consensus Conference of the Task Force for Thoracic Organ Transplantation of the German Cardiac Society.

Angiograms of cardiac transplant (HTx) recipients were to be evaluated in a ring experiment and a joint consensus on criteria of angiographic evaluation of coronary arteries of HTx patients was to be reached. Twenty-four coronary angiograms from 11 hospitals were circulated. One hundred eighty-eight blinded evaluations were returned.

Heart transplantation at the Deutsches Herzzentrum Berlin.

The Deutsches Herzzentrum Berlin is one of the largest transplant centers in Germany with more than 1700 transplant procedures, more than 170 being procedures in children, in patients from the beginning of life to 71 years of age. Survival rates during the early and intermediate follow-up are lower than in international data; however, long-term survival at 15 years or more is similar. Discrepant survival rates derive mainly from the organ shortage that resulted in the development of a different allocation system in Germany as compared to North America and in the increasing number of patients undergoing the bridge-to-transplant concept to move the patient to transplantability.

Reduction of arteriosclerotic nanoplaque formation and size by n-3 fatty acids in patients after valvular defect operation.

Background/methods: Coating a silica surface with the isolated lipoprotein receptor heparan sulfate proteoglycan (HS-PG) from arterial endothelium and vascular matrices, we could observe the very earliest stages of arteriosclerotic plaque development by ellipsometric techniques in vitro (patent EP 0 946 876). This so-called nanoplaque formation is represented by the ternary aggregational complex of the HS-PG receptor, lipoprotein particles and calcium ions. The model was validated in several clinical studies on statins in cardiovascular high-risk patients applying their native blood lipoprotein fractions.

Bronchogenic cyst of the interatrial septum presenting as atrioventricular block.

Bronchogenic cysts are congenital lesions that are a remnant from abnormal budding of the embryonic foregut. These cysts are usually single; most cases are either asymptomatic or present with respiratory symptoms. A 43-year-old woman presented with intermittent type II atrioventricular block during cholecystectomy.

Attenuation of transplant arteriosclerosis with clopidogrel is associated with a reduction of infiltrating dendritic cells and macrophages in murine aortic allografts.

Background: Monotherapy with clopidogrel reduced the formation of transplant arteriosclerosis in a murine aortic allograft model. However, the underlying immunologic mechanisms are still unknown.

Methods: Fully major histocompatibility complex-mismatched C57BL/6 (H2b) donor aortas were transplanted into CBA.

Beneficial effect of female gender on long-term survival after heart transplantation.

Background: We aimed to test whether stenotic microvasculopathy affects the more beneficial course in female cardiac transplant recipients.

Methods: We studied 873 patients (35/151 premenopausal women aged < or =40 years) who underwent primary heart transplantation. In 7750 biopsies harvested within the first posttransplant year endothelial disease and stenotic microvasculopathy were evaluated by light microscopy (Hematoxylin and Eosin).

Quilty in biopsy is associated with poor prognosis after heart transplantation.

We tested if Quilty (endocardial infiltration of lymphocytes) in routinely processed endomyocardial biopsy is associated with poor outcome after heart transplantation (HTx). Biopsies (n=9829) harvested within the first post-transplant year from 938 patients (778 men, mean age 49 years) were evaluated for Quilty and acute cellular rejection (according to the International Society for Heart and Lung Transplantation, ISHLT, classification). Transplant vasculopathy was evaluated by coronary angiography, and severe stenosis was found in 19% of patients.

Coronary flow reserve measurement detects transplant coronary artery disease in pediatric heart transplant patients.

Background: Cardiac allograft vasculopathy (CAV) in patients who have undergone heart transplantation leads to graft dysfunction and is still the major concern for long-term survival. Evaluation of coronary flow velocity reserve (CFR) has been established for diagnosis of CAV. Systemic application of adenosine vs intracoronary testing for CFR has been validated in adults; however, its accuracy in pediatric patients has not yet been proven.

Quilty indicates increased risk for microvasculopathy and poor survival after heart transplantation.

Background: The impact of Quilty (sub-endocardial infiltration of lymphocytes) on the development of stenotic microvasculopathy and outcome after heart transplantation has not yet been evaluated.

Methods: Biopsies (n = 9,713) obtained within the first post-transplant year from 873 patients (722 men, age 49.3 +/- 0.

A decade of percutaneous coronary interventions in cardiac transplant recipients: a monocentric study in 160 patients.

Background: Transplant vasculopathy is a long-term complication of cardiac transplantation. Percutaneous transluminal coronary angioplasty (PCI) is a method of choice for local revascularization that is also increasingly used in heart transplant patients.

Methods: Between October 1989 and November 2006, 160 adult cardiac transplant recipients (19 women) with mean age at heart transplantation of 47 +/- 12 years underwent PCI in 502 coronary segments during 319 catheterizations (balloon only, 209; bare metal stents, 227, drug-eluting stents, 66).

Prognostic impact of microvasculopathy on survival after heart transplantation: evidence from 9713 endomyocardial biopsies.

Background: Epicardial vasculopathy has been shown to be associated with poor outcome after heart transplantation. We demonstrate that histologically proven stenotic microvasculopathy is a novel prognostic factor for long-term survival.

Methods And Results: In 9713 biopsies harvested within the first posttransplantation year from 873 patients (83% male; mean age, 49.

Prevalence of graft vessel disease after paediatric heart transplantation: a single centre study of 54 patients.

The study tested the prevalence of graft vessel disease (GVD) in 54 paediatric heart transplant (HTx) patients (32 male, age 0-17 years) who underwent coronary angiographic investigations (N=117). These were evaluated according to the Stanford classification and additional criteria (peripheral obliterations, diameter fluctuations, pathologic tapering) were applied for risk assessment (no GVD/minimal lesions, GVD without Stanford lesions, accelerated GVD). In H&E stainings from right ventricular endomyocardial biopsies (EMB=169) diagnosis of acute cellular rejection (ACR, ISHLT) and microvasculopathy were performed.

Observational study with everolimus (Certican) in combination with low-dose cyclosporine in de novo heart transplant recipients.

Background/methods: This observational study reports on immunosuppression with cyclosporine (CsA) in 38 de novo heart transplant recipients receiving everolimus compared with 14 patients receiving mycophenolate mofetil (MMF).

Results: Mean (+/- SD) everolimus C0 blood levels remained stable within 5 to 7 ng/ml. Mean CsA C0 blood levels were reduced by 47%, from 240 +/- 57 ng/ml at 2 weeks post-transplant to 128 +/- 38 ng/ml at Month 6 and by 58% to 101 +/- 26 ng/ml at Month 12 in the everolimus group, compared to 18% from 246 +/- 54 ng/ml at 2 weeks post-transplant to 201 +/- 48 ng/ml at Month 6 and by 35% to 160 +/- 41 ng/ml in MMF patients.

Clopidogrel reduces the development of transplant arteriosclerosis.

Background: Transplant arteriosclerosis, the hallmark feature of chronic rejection, is still the major limiting factor for the long-term success of heart transplantation. Platelets have been implicated to play a role in the pathogenesis of this disease. Therefore the aim of this study was to investigate whether platelet inhibition alone has a positive effect on the development of transplant arteriosclerosis.