Felix Gramley

Hypoxia and Myocardial Remodeling in Human Cardiac Allografts: A Time-course Study

BACKGROUND Cardiac allografts are known to develop myocardial fibrosis, which may be a cause of progressive cardiac dysfunction. Apart from the renin-angiotensin and transforming growth factor-beta system, hypoxia has been proposed as an important player in the pathogenesis of fibrosis, but its significance remains unclear. This study examines the degree of myocardial fibrosis, cellular remodeling and hypoxic signaling over a time-course of 10 years after human cardiac allograft transplantation. METHODS Serial right ventricular biopsies of 57 patients were collected in 6-month intervals after cardiac transplant surgery for a total of 10 years to allow a retrospective longitudinal analysis. Over this period, tissue remodeling, including interstitial fibrosis and cellular changes, were determined morphometrically. Immunohistochemistry (IHC) was used to analyze expression of the following hypoxia-related proteins: hypoxia-induced factor 1-alpha (HIF1alpha); the oxygen sensor prolyl hydroxylase 3 (PHD3); and vascular endothelial growth factor (VEGF). RESULTS Fibrosis increased significantly from 12.6 +/- 6.5% at the point of transplantation throughout follow-up to 28.8 +/- 7.7% at 10 years. The DNA content and number of nuclei changed over the period of follow-up, displaying signs of cellular hypertrophy and a loss of myocytes. Whereas HIF1alpha expression revealed a U-shaped pattern with both early and late elevation during fibrogenesis, PHD3 and VEGF expression patterns showed a gradual increase with PHD3 decreasing again in later fibrogenesis. CONCLUSIONS In cardiac allografts, extensive and progressive tissue remodeling is present. Hypoxia may play a role in this process by up-regulating HIF1alpha and leading to differential regulation of pro-angiogenic signals.

Catheter ablation of atrial fibrillation: Radiofrequency catheter ablation for redo procedures after cryoablation

AIM To evaluate the effectiveness of two different strategies using radiofrequency catheter ablation for redo procedures after cryoablation of atrial fibrillation. METHODS Thirty patients (paroxysmal atrial fibrillation: 22 patients, persistent atrial fibrillation: 8 patients) had to undergo a redo procedure after initially successful circumferential pulmonary vein (PV) isolation with the cryoballoon technique (Arctic Front Balloon, CryoCath Technologies/Medtronic). The redo ablation procedures were performed using a segmental approach or a circumferential ablation strategy (CARTO; Biosense Webster) depending on the intra-procedural findings. After discharge, patients were scheduled for repeated visits at the arrhythmia clinic. A 7-day Holter monitoring was performed at 3, 12 and 24 mo after the ablation procedure. RESULTS During the redo procedure, a mean number of 2.9 re-conducting pulmonary veins (SD ± 1.0 PVs) were detected (using a circular mapping catheter). In 20 patients, a segmental approach was sufficient to eliminate the residual pulmonary vein conduction because there were only a few recovered pulmonary vein fibres. In the remaining 10 patients, a circumferential ablation strategy was used because of a complete recovery of the PV-LA conduction. All recovered pulmonary veins could be isolated successfully again. At 2-year follow-up, 73.3% of all patients were free from an arrhythmia recurrence (22/30). There were no major complications. CONCLUSION In patients with an initial circumferential pulmonary vein isolation using the cryoballoon technique, a repeat ablation procedure can be performed safely and effectively using radiofrequency catheter ablation.

Catheter ablation of atrial fibrillation facilitated by preprocedural three-dimensional transesophageal echocardiography : long-term outcome

AIM To evaluate the long-term outcome of catheter ablation of atrial fibrillation (AF) facilitated by preprocedural three-dimensional (3-D) transesophageal echocardiography. METHODS In 50 patients, 3D transesophageal echocardiography (3D TEE) was performed immediately prior to an ablation procedure (paroxysmal AF: 30 patients, persistent AF: 20 patients). The images were available throughout the ablation procedure. Two different ablation strategies were used. In most of the patients with paroxysmal AF, the cryoablation technique was used (Arctic Front Balloon, CryoCath Technologies/Medtronic; group A2). In the other patients, a circumferential pulmonary vein ablation was performed using the CARTO system [Biosense Webster; group A1 (paroxysmal AF), group B (persistent AF)]. Success rates and complication rates were analysed at 4-year follow-up. RESULTS A 3D TEE could be performed successfully in all patients prior to the ablation procedure and all four pulmonary vein ostia could be evaluated in 84% of patients. The image quality was excellent in the majority of patients and several variations of the pulmonary vein anatomy could be visualized precisely (e.g., common pulmonary vein ostia, accessory pulmonary veins, varying diameter of the left atrial appendage and its distance to the left superior pulmonary vein). All ablation procedures could be performed as planned and almost all pulmonary veins could be isolated successfully. At 48-mo follow-up, 68.0% of all patients were free from an arrhythmia recurrence (group A1: 72.7%, group A2: 73.7%, group B: 60.0%). There were no major complications. CONCLUSION 3D TEE provides an excellent overview over the left atrial anatomy prior to AF ablation procedures and these procedures are associated with a favourable long-term outcome.