Checklist identification of candidates for systemic therapy in adult patients with atopic dermatitis in Germany: A multicentre study.

BACKGROUND: The German S2k guideline is the first to include a checklist that captures atopic dermatitis (AD) signs and symptoms as well as the lack of treatment response to identify patients eligible for systemic therapy. OBJECTIVES: Identifying candidates for a start/switch of systemic therapy in adult AD patients in Germany by applying the S2k guideline's checklist. METHODS: In this German multicentre, cross-sectional, non-interventional study (German Clinical Trials Register number: DRKS00023296), adult patients with mild to severe AD were enrolled at dermatological outpatient clinics and offices between April and October 2021. Demographics, clinical characteristics and quality of life were collected using questionnaires during one single visit. Eligibility for a start/switch of systemic AD therapy was evaluated according to the criteria of the German S2k guideline's checklist. RESULTS: Atopic dermatitis patients (575) were included in the analysis. One hundred and sixty-four patients (28.5%) received systemic (SYS) AD therapy and 411 patients (71.5%) did not (TOP). Of the TOP therapy patients, 38.7% were eligible to start systemic AD therapy, and about half of those (49.1%), were scheduled to start systemic AD therapy. The most frequent reason deciding against a systemic therapy was the patient's wish. Although 29.3% of SYS patients were eligible for a switch according to the criteria of the German S2k guideline's checklist, the majority (81.3%) did not switch AD therapy. CONCLUSIONS: This is the first study on the implementation of the German S2k guideline's checklist in everyday care of AD patients in Germany. More than one-third of the TOP patients were identified as eligible for systemic treatment. By applying the guideline's checklist criteria, another one-third of SYS patients may have benefited from a change of current systemic therapy. The use of the German S2k guideline's checklist in routine care represents an important tool to ensure effective patient care and identify inadequately treated patients.

Curcumin Micelles Improve Mitochondrial Function in a Mouse Model of Alzheimer's Disease.

Preventive strategies for late-onset Alzheimer's disease (AD) should start early at a prodromal stage. Mitochondrial dysfunction has been found to play an important role in the initiation of both aging and the pathogenesis of Alzheimer's disease. Curcumin, a widely used spice and food-coloring agent, is a polyphenol derived from the rhizome of Curcuma longa. It is known to have anti-oxidant, anti-inflammatory, and anti-protein-aggregate activities which are usually considered beneficial for mitochondrial function. We assessed brain mitochondrial function and concentrations of soluble Aß40 in a mouse model of AD (Thy1-APP751SL transgenic mice) after 3-week administration of curcumin micelles. Curcumin micelles are a newly developed formulation that account for increased curcumin bioavailability. Curcumin treatment had positive effects on mitochondrial membrane potential and respiratory control ratio. Additionally, it decreased levels of soluble Aß40 in brains of Thy1-APPSL transgenic mice. Hence, curcumin micelles are a promising neutraceutical for the prevention of AD.

Neuroprotection by bilobalide in ischemia: improvement of mitochondrial function.

Bilobalide, an active constituent of Ginkgo biloba, is known to have neuroprotective properties, but its mode of action remains unclear. In this study, bilobalide significantly reduced brain damage in mice (indicated by TTC staining) when given before transient middle cerebral artery occlusion (tMCAO). As measured by microdialysis in the ischemic striatum, local perfusion with bilobalide (10 microM) reduced ischemia-induced glutamate release by 70% while glucose levels were not affected. Mitochondria isolated from ischemic brain showed a decrease of respiration compared to non-ischemic controls. Treatment with bilobalide (10 mg/kg) before tMCAO improved respiratory capacity of complex I significantly when measured ex vivo. In addition, mitochondrial swelling induced ex vivo by calcium was used to estimate opening of the mitochondrial permeability transition pore. In this assay, the changes induced by tMCAO were completely reversed when mice had received pretreatment with bilobalide. We conclude that neuroprotection by bilobalide involves a mechanism in which the drug reverses ischemia-induced changes in mitochondria, leading to a reduction of glutamate release.

Myocardial infarction: an important factor for surgical decision making?

BACKGROUND: Recent myocardial infarction has been identified as a risk factor and is currently used as a strong predictor in different scores. The aim of our study was to determine whether the impact of myocardial infarction, especially acute myocardial infarction, is still strong enough to justify a restrictive indication for isolated CABG procedure in patients with significant coronary artery disease. METHODS: 10 272 patients underwent isolated CABG at a single institution. A 10-year follow-up was performed with a completeness of 97.2 %. RESULTS: 6 107 (59.5 %) of the patients had a history of myocardial infarction. A stratified Kaplan-Meier analysis demonstrates a significantly worse survival for patients with myocardial infarction (chi-square value: 36.7, P < 0.0001). At a further differentiation for no myocardial infarction (n = 4 165), myocardial infarction > 90 days (n = 4 578), myocardial infarction up to 90 days (recent myocardial infarction) (n = 1 266) and ongoing acute myocardial infarction up to 15 days (n = 263), indicated a higher mortality for the more recent infarction in the univariate analysis. However, if patients with acute myocardial infarction in the past 6 years were analyzed separately, their risk remained at the same level as patients with non-acute myocardial infarction over the total observation period. Furthermore, propensity score matching revealed no statistical significant difference in the outcome of the patients. CONCLUSIONS: Structural myocardial damage represents a risk factor for survival after isolated CABG in univariate analysis. More appropriate statistical methods indicate a time-dependent loss of statistically relevant differences between patients with or without myocardial infarction prior to CABG. This is also true for "recent" myocardial infarction which is still part of current scores.

Surgical treatment of long-segment tracheal anomalies in infants and children.

BACKGROUND: Tracheal stenosis in combination with vascular and/or cardiac anomalies is a life-threatening condition in infants and children presenting with severe symptoms of airway obstruction. The optimal surgical treatment of these cases remains controversial. OBJECTIVES: We present here a group of infants and children with combined tracheal malformations and vascular and/or cardiac anomalies. More than 30 % of the stenotic trachea was resected in a subgroup of the patients. A reconstruction with end-to-end anastomosis was achieved on the basis of extensive mobilization of the whole tracheobronchial tree and use of CPB. METHODS: The clinical outcome in 37 children with a median age of 8 (1 - 72) months was analyzed retrospectively. The patients presented with severe airway obstruction in combination with congenital heart defects and/or vascular anomalies. Cardiac catheterization, bronchoscopy and thoracic computer tomography were performed prior to operation. The operations were performed under CPB and consisted of tracheal resection with end-to-end anastomosis or external stabilization. Associated intracardiac and vascular anomalies were repaired simultaneously. RESULTS: All but 1 patient survived and had a straightforward recovery. The patients were extubated under bronchoscopic control with a median intubation time after airway repair of 12.2 days. The average follow-up was 8.4 years (1 - 14 years) and the surviving patients did not show signs of restenosis clinically. A segment longer than 30 % of the tracheal length was resected and reconstructed with end-to-end anastomosis in 57 % of the patients (12 of 21 patients). CONCLUSIONS: Our experience demonstrates that resection of tracheal stenosis and end-to-end anastomosis can be achieved successfully even in cases with stenosis of more than 30 % of the total tracheal length. The use of CBP allowed extensive mobilization of the tracheobronchial tree and resection with end-to-end tension-free anastomotic reconstruction.

Long-term results after coronary artery reconstructive surgery.

BACKGROUND: Diffuse coronary artery disease, multiple consecutive stenoses and complex lesions are a common finding in coronary surgery. Coronary reconstructive surgery in terms of extended anastomoses with or without thromboendarterectomy is still controversially discussed. The aim of this study was to evaluate the long-term results of patients who underwent coronary reconstruction. METHODS: Between January 1995 and June 2004, 640 consecutive, unselected patients underwent isolated CABG with coronary reconstructive surgery of the LAD at a single institution. A cross-sectional long-term follow-up was performed with a completeness of 99.2 %. Questionnaires were sent to all patients with a response rate of 83.2 % (n = 533). RESULTS: 147 of the 640 patients (22.9 %) died during up the follow-up period which was up to 10 years. Of the 371 patients who responded to the questionnaires, the status of 54 patients (15.9 %), predominantly those with a preoperative lower NYHA class, remained unchanged, while 294 patients (79.2 %) improved by at least one NYHA class. Repeat angiography was performed in 80 patients (15.7 %). Indications for percutaneous coronary intervention for the LAD arose in 4 cases (0.8 %); the interventions were performed in the proximal (n = 2) or distal (n = 1) LAD and one intervention affected the anastomotic area. Redo CABG was necessary in 3 patients (0.5 %). CONCLUSIONS: Coronary reconstruction in patients with complex coronary morphology and advanced diffuse CAD is in an additionally investigated subgroup of patients associated with a satisfying graft patency and excellent long-term results in terms of survival, NYHA class and reintervention rate.

Differentiated expression patterns of growth factors in routine formalin-fixed endomyocardial biopsies in the early postoperative phase after heart transplantation.

BACKGROUND: Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) seem to play a key role in immunological reactions shortly after heart transplantation (HTx). The aim of this study was to analyze the time course of the expression of PDGF A and B, PDGF-receptor alpha (PDGF-Ralpha) and beta, aFGF, and bFGF on formalin-fixed routine endomyocardial biopsies. PATIENTS AND METHODS: Right ventricular endomyocardial biopsies were obtained from 36 heart transplant recipients up to 2 weeks after HTx. According to the clinical course in the first postoperative year, 3 groups were formed: (1) clinically uneventful course (n = 12); (2) cardiac/systemic infections (n = 12); (3) acute rejection (n = 12). The growth factor expression was examined immunohistochemically. RESULTS: In the early phase after HTx, PDGF A, PDGF B, PDGF-Ralpha, and PDGF-Rbeta were predominantly expressed in endothelial cells. The main expression of PDGF-Ralpha and bFGF was found in cardiomyocytes, endothelial cells, and smooth muscle cells. During the first 2 postoperative weeks, PDGF A, PDGF B, and PDGF-Rbeta showed a similar time course of expression: A significantly elevated expression in the first week was followed by a decrease in the second week. In the rejection group, PDGF A was significantly elevated after the first week. CONCLUSIONS: The increased expression of PDGF in the first postoperative week can be interpreted as an unspecific reaction to peritransplant injury. The prolonged expression of PDGF A, PDGF B, and PDGF-Rbeta showed that there were ongoing immunological reactions in the transplant during week 2. The persistence of elevated PDGF A expression might be of prognostic value in terms of a risk factor for either infection or rejection.

Three-dimensional assessment of left ventricular geometry and annular dilatation provides new mechanistic insights into the surgical correction of ischemic mitral regurgitation.

BACKGROUND: The aim of this study was to investigate the relationship between LV geometry, annular shape and the amount of regurgitation in patients with ischemic mitral regurgitation (group 1, n = 30) compared to patients with primary mitral valve lesions (group 2, n = 30). METHODS: LV geometry was assessed by the sphericity index, i.e., LV volume divided by the volume of a sphere with a diameter equal to the longest axis. Annular geometry was evaluated by diameters, areas and their percentual shortening. The degree of mitral regurgitation was assessed as jet volumes by 3D-echocardiography. RESULTS: Group 1 showed significantly larger longitudinal (54.3 +/- 3.1 vs. 40.9 +/- 2.6 mm) and antero-posterior (32.2 +/- 3.3 vs. 27.1 +/- 2.9 mm) annulus diameters and areas (993.3 +/- 66.6 vs. 702.1 +/- 47.9 mm (2)) than group 2. No asymmetric annular enlargement was found in either group. Annular enlargement correlated to the degree of mitral regurgitation in group 1 but not in group 2. Annular area shortening was significantly impaired in group 2 and the sphericity index was larger in group 1 than in group 2. In group 1, the sphericity index was significantly correlated to the degree of mitral regurgitation (r = 0.87; P < 0.001). CONCLUSIONS: These findings suggest that ischemic mitral regurgitation was mostly associated with a global left ventricular enlargement, in which annulus dilatation and its reduced contraction play a significant role.

The Eurotransplant High-Urgency Heart Transplantation Program: an option for patients in acute heart failure?

OBJECTIVE: The Eurotransplant High-Urgency (HU) Heart Transplantation Program allows urgent heart transplants to be carried out in rapidly deteriorating patients with acute-to-chronic heart failure on the elective waiting list. But do the results of HU heart transplantation justify performing primary heart transplantation in these critically ill patients and offer an acceptable outcome? METHODS: Between 2000 and 2004, 64 heart transplantations (HTx) (32 elective and 32 HU-HTx) were performed in our department. After having been accepted in an auditing process based on HU criteria, intensive care patients in NYHA functional class IV (cardiac index 1.7 l/min/qm BS), in end-organ failure (creatinine 1.5 mg/dl), and with catecholamine dependence (dobutamine 8 microg/kg/min), are given priority with respect to organ allocation, and their data were compared to data from elective patients from the same period. RESULTS: HU requests were accepted in 97 % of cases. Two requests were not accepted, and both patients with contraindications for assist device implantation died within one week. The HU patients were 100 % in NYHA class IV, 93 % of the elective patients were in NYHA class III. Waiting time on the HU list was 13 days, and 7 of these patients died before HTx. Following heart transplantation, survival rates at 30 days and at one year of the HU group were 88 % and 85 % versus 94 % and 93 % in the elective group. CONCLUSIONS: This study shows that end-stage heart failure patients in the HU program can be transplanted primarily with good results if an organ is available in time. We are still in the position where the HU program only manages the organ shortage; there are still too many patients on the waiting list who die before receiving a donor organ.

Coronary reconstructive surgery versus coronary artery bypass grafting--a documentation gap.

OBJECTIVE: Over the last years, there has been a clear trend that an increasing number of patients are admitted for CABG with advanced disease, complex pathomorphological alterations and impaired left ventricular function. The necessity of performing extensive reconstructive coronary surgery rather than coronary bypass grafting, in its original sense, is not appropriately documented by the current version of the German Documentation System for Cardiac Surgery, nor in other national and international documentation systems. PATIENTS AND METHODS: 5821 consecutive, unselected patients underwent isolated CABG from 7/1995 through 12/2003 at a single institution. A closing date follow-up procedure up to 8 years postoperatively was performed with a completeness of 98.8%. RESULTS: The need for reconstructive surgery in terms of extended anastomoses with or without coronary endarterectomy has doubled in our patients since 1995 and is steadily increasing with 15.7 % (n=102) of these patients requiring such surgery in 2003. Current documentation does not allow any prediction of complex coronary morphology. The Kaplan-Meier survival curve reveals no substantial difference between patients with and without coronary reconstructive surgery up to 8 years after CABG. CONCLUSION: The increase of complexity in CABG procedures currently remains undetected, since preoperative imaging methods often fail to predict complex coronary morphology. Survival after coronary reconstructive surgery is comparable to that of "classical" CABG. Therefore, a standardized documentation is required to evaluate surgical results and to contribute to the improvement of medical decision-making which presupposes valid data.

Intravital microscopy of pulmonary microcirculation after single lung transplantation in pigs.

BACKGROUND: Pulmonary reperfusion injury is a significant risk factor following lung transplantation (LTx). Unfortunately, in vivo observations and quantitative analyses of the pulmonary microcirculation following LTx are technically demanding. METHODS: Pigs, weighing 18 to 22 kg, served as the laboratory animals. The left lung was harvested and preserved using donor aortic vessel segments, the pulmonary artery, and the cuff of the lung veins were extended. After 4 hours of ischemia, the lungs were transplanted by direct connection of the conduits to the left atrial appendage and the left pulmonary artery of the recipient. The lungs were placed extrathoracically and ventilated. The recipient left lung was excluded. With this procedure, mechanical trauma to the lung and moving artefacts were avoided. Intravital microscopic observation became feasible. RESULTS: Following reperfusion, oxygenation of pulmonary venous blood was excellent. However, blood flow distribution was significantly reduced to the transplanted lung compared with the native right recipient lung. Pulmonary vascular resistance was significantly increased, dropping from 3500 to 1000 dynes x s x cm(-5) during reperfusion compared to a value of 500 for the native right lung. The pulmonary microcirculation showed a significant number of no-reflow areas with extremely reduced red blood cell velocities. Greater than 90% of microvessels (<30 microm) showed velocities below 0.1 mm/sec. In conclusion, microvascular injury seems to be a major pathogenic factor for the development reperfusion failure. Quantification of alterations within the microvasculature may shed light on various treatment modalities that reduce perfusion failure.

Bridge to operation with the GPIIb/IIIa inhibitor abciximab in high-risk coronary patients.

BACKGROUND: Glycoprotein-IIb/IIIa inhibitors are now frequently used in the cardiological treatment of high-risk coronary patients even if the patient is considered suitable for surgical intervention. However, there is no consensus whether GPIIb/IIIa inhibitors should be stopped before operation because of an increased risk of bleeding or if surgery should even be delayed until the anticoagulating effect subsides. METHODS: From June 2002 to August 2003 140 patients who had to undergo primary aorto-coronary bypass for ongoing myocardial ischemia were enrolled in the present study. The patients received either clopidogrel, aspirin and heparin or additionally abciximab until operation. RESULTS: Although the intraoperative need for blood products was higher in the abciximab group, there was no significant difference in postoperative blood loss. The hemodynamic situation of the abciximab patients after the operation was better compared to the other groups. 30-day mortality was not increased when compared to the elective control group (6.7 % vs. 6.1 %). CONCLUSION: The GPIIb/IIIa inhibitor abciximab can be safely used as a bridge to operation and results in a better hemodynamic outcome in high-risk coronary patients while reducing the incidence of major ischemic events.

Right ventricular expression of extracellular matrix proteins, matrix-metalloproteinases, and their inhibitors over a period of 3 years after heart transplantation.

Fibrillar collagens I and III, nonfibrillar collagen IV, and the glycoproteins fibronectin and laminin, are elements of the myocardial extracellular matrix (ECM). Alterations in the normal concentrations and ratios of these elements may reflect remodeling in response to physiologic stress. In the case of patients' post-heart transplantation (HTx), specific patterns of alteration may herald myocardial dysfunction. Right ventricular biopsies were taken from the same 28 HTx patients before implantation and 1 week, 2 weeks, and 1, 2, and 3 years after HTx. The above-noted five ECM proteins, six matrix metalloproteinases (MMPs) and two of their tissue inhibitors (TIMPs) were detected by immunohistochemistry and scored as cells per square millimeter or semiquantitatively. The total connective tissue fibers were detected by connective tissue stain and morphometry. Variations in these ECM components were followed in the same patient cohort over 3 years. In summary, during the first 2 weeks after HTx, a predominant increase in connective tissue occurred. Increases in MMP-8 and MMP-9 were found. By 3 years after transplantation, there was a decrease of connective tissue fibers and a significant reduction of all ECM components and an increase in MMPs and TIMPs. These findings may reflect a pattern of remodeling specific to the transplanted heart.

Coronary fistula of right coronary artery to vena cava superior and ectasia of pulmonary artery.

We report on a patient with coronary heart disease, a coronary fistula of right coronary artery to vena cava superior and pulmonary hypertension. Combined with coronary artery revascularization, the coronary fistula was closed successfully.

Extracellular matrix proteins and matrix metalloproteinases differ between various right and left ventricular sites in end-stage cardiomyopathies.

This study was undertaken to investigate whether there might be differences in the distribution of extracellular matrix (ECM) proteins and matrix metalloproteinases (MMPs), depending on their specific sites within the heart. We investigated 33 explanted human hearts, 15 with dilated cardiomyopathy (DCM) and 18 with ischemic cardiomyopathy (ICM). Transmural samples from the right ventricle, the interventricular septum and the left ventricle, either from near the apex or from near the base were taken from every heart. Frozen sections were processed for connective tissue staining and immunohistochemistry for collagens type I, III, IV, laminin and fibronectin, as well as MMP-1, -2 and -9. Volume densities of laminin in ICM as well as of fibronectin and collagen types I and IV in DCM showed significant differences between right and left ventricular sites. The volume densities of matrix proteins usually did not reveal significant differences among the three left ventricular sites tested in both DCM and ICM. MMPs partly showed differences between the right and the left ventricular myocardium. These results suggest that the distributions of ECM proteins and MMPs differ between the two ventricles in both end-stage DCM and ICM. This gives rise to the hypothesis that a specific pattern of ECM degradation exists in the right and left ventricular myocardium.

Poly-ADP-ribose polymerase inhibition reduces mesenteric injury after cardiopulmonary bypass.

BACKGROUND: We investigated the effects of PARS inhibition on intestinal injury in a canine model of cardiopulmonary bypass (CPB). METHODS: Twelve dogs underwent 90 minutes of hypothermic CPB. 6 dogs received 5 mg/kg PJ34, a selective PARP inhibitor during CPB, 6 vehicle-treated animals served as controls. Mesenteric blood flow (MBF) and mesenteric vascular resistance (MVR) were measured before and 60 minutes after weaning from CPB. Endothelium-dependent vasorelaxation to acetylcholine (ACH) and endothelium-independent vasorelaxation to sodium-nitroprusside (SNP) were expressed as percent change of MVR. In addition, mesenteric creatine kinase (CK) and lactate release were determined. RESULTS: Baseline hemodynamics, MBF, response to ACH (- 41 +/- 3 vs. - 55 +/- 6 %) and SNP (- 60 +/- 2 vs. - 56 +/- 4 %) did not differ significantly between the groups. The response to ACH decreased significantly in the control group while it remained unchanged in the PJ34 group (- 29 +/- 5 vs. - 46 +/- 9 %, p < 0.05). The response to SNP did not change. Mesenteric CK release (325 +/- 99 vs. 16 +/- 10 U/l, p < 0.05) and lactate production (0.96 +/- 0.17 vs. 0.4 +/- 0.2 mmol/l, p < 0.05) were significantly lower in the PJ34 group. CONCLUSION: PARP inhibition prevents CPB-induced mesenteric endothelial dysfunction and tissue damage.

Expression and activity of matrix metalloproteinase-2 in calcific aortic stenosis.

Calcific aortic stenosis is the main heart valve disease in the elderly, leading to massive focal calcification and thickening of the valve cusps. Matrix metalloproteinases (MMPs) are thought to contribute to this process. Therefore, the study assessed the expression of the gelatinases MMP-2 and MMP-9 and the endogenous tissue inhibitor of metalloproteinase (TIMP)-2 as well as the gelatinolytic activity in normal and stenotic valves. Human tricuspid aortic valves with and without calcific aortic stenosis were studied by immunohistochemistry for MMP-2, MMP-9 and TIMP-2. The gelatinolytic activity in native valve sections was assessed by gelatin in situ zymography with or without addition of the MMP activator p-aminophenymercuric acetate (APMA). Staining intensities for MMP-2 and TIMP-2 were elevated in stenotic valves as compared to controls. Minor staining of MMP-9 was present exclusively in stenotic valves. The morphologic distribution of gelatinolytic activity was comparable to the staining pattern of MMP-2, and since MMP-9 immunostaining demonstrated only a low number of positive cells, the observed gelatinolytic activity is likely due to MMP-2. Gelatinolytic activity was low in normal valves but significantly increased by the MMP activator APMA. In contrast, stenotic valves showed a strong basal gelatinolytic activity that could not be significantly enhanced by APMA suggesting that MMP-2 is present as a latent pro-enzyme in normal valves and activated in stenotic valves. Thus, MMP-2 might be involved in the matrix remodeling during calcific aortic stenosis.

Long-term results after repair of truncus arteriosus communis in neonates and infants.

BACKGROUND: We reviewed our experience of truncus arteriosus communis (TAC) repair. METHODS: Between 05/90 and 10/01, 16 patients underwent complete repair of TAC (primary repair: group I, 12 patients, secondary repair: group II, 4 patients). Age was 2.4 months [5 days-8.8 months] (median [range]) in group I, and 8.3 [5.6-13.5] years in group II. Continuity from the right ventricle to the pulmonary artery was achieved using a valved conduit. All patients had regular follow-up examinations. RESULTS: There was one early death in each group (12.5%). Follow-up was 9 [1.2-12.7] years. Valved conduit failure occurred in 8 patients (67 %) in group I (group II, 1 patient, 33 %) requiring replacement at 2.5 [0.3-4.3] years (group II, 5.8 years). Severe neo-aortic valve regurgitation after truncal valve repair was observed in one patient, requiring valve replacement at 8.5 years in association with repeat homograft replacement (group I). Actual echocardiographic examination revealed normal ventricular function. Moderate conduit dysfunction was noted in 2 patients (group I). CONCLUSIONS: Complete repair of truncus arteriosus communis can be performed with excellent long-term results.

Pathological changes of the myocardium in patients after atrial repair for transposition of the great arteries: a possible explanation for left ventricular dysfunction after secondary arterial switch.

BACKGROUND: Patients with transposition of the great arteries who underwent an atrial repair in infancy are likely to develop right ventricular dysfunction later in life. For these patients a two-stage arterial switch operation has been advocated by some groups but mortality even from the initial pulmonary banding procedure for retraining the left ventricle has been reported to be considerable. We asked whether pathological alterations of the left ventricular myocardium could explain for the failure of the left ventricle observed in patients after two-stage arterial switch operations. METHODS: Twelve patients aged 16.9 [8-25.4] years (median [range]) with transposition of the great arteries after atrial repair in infancy were enrolled. Median follow-up interval was 15.8 [7.8-22.1] years. Measurements of right and left ventricular systolic function were performed by echocardiography. In addition all patients underwent cardiac catheterization. Endomyocardial biopsies were taken from the right and left ventricle and examined histopathologically. RESULTS: Two out of twelve patients showed mildly reduced systolic right ventricular function. Systolic function of the left ventricle was normal in all patients on echocardiography but six out of twelve patients showed clusters of fibrous and fatty degeneration on biopsy specimens obtained from the left ventricle. CONCLUSION: We conclude that degenerative left ventricular myocardial changes could serve as an explanation for left ventricular failing when retraining the left ventricle during two-stage arterial switch operations.