Catheter ablation of persistent atrial fibrillation : Beneficial effect of a short-term adjunctive amiodarone therapy on the long-term outcome.

BACKGROUND: Catheter ablation has become the first line therapy in patients with symptomatic, recurrent, drug-refractory atrial fibrillation. Circumferential pulmonary vein ablation is still the standard approach in these patients. However, the results are not very favorable (especially in patients with persistent atrial fibrillation). Therefore, more complex ablation strategies and the usefulness of (short-term) adjunctive antiarrhythmic drug therapy are a matter of discussion. The aim of this study was to analyze whether short-term amiodarone therapy after catheter ablation (3 months) has a positive effect on the success rates after circumferential pulmonary vein ablation in patients with persistent atrial fibrillation. METHODS: A total of 230 consecutive patients with symptomatic persistent atrial fibrillation underwent a circumferential pulmonary vein ablation procedure (using the NAVX or CARTO system). Catheter ablation of the right or left atrial isthmus and a linear lesion in the roof of the left atrium were only performed in selected patients with documented episodes of atrial fibrillation. In 115 patients, a short-term adjunctive antiarrhythmic drug therapy with amiodarone was initiated immediately prior to the ablation procedure (for the first 3 months group A). In the remaining 115 patients, no antiarrhythmic drug therapy was administered except for beta blockers (group B). RESULTS: Out of 115 patients 19 (16.5%) in group A and 34 (29.6%) in group B experienced an arrhythmia recurrence within the first 3 months after ablation requiring electrical cardioversion (P = 0.03; blanking period). One year after the ablation procedure 81.7% of patients in group A (94/115) and 73.0% of patients in group B (84/115) were free from further arrhythmia recurrences (P = 0.16). The success rate 2 years after catheter ablation was 76.5% (no arrhythmia recurrence in 88/115 patients) in group A and 63.5% in group B (no arrhythmia recurrence in 73/115 patients; P = 0.04). There were no major complications during long-term follow-up. CONCLUSION: Adjunctive short-term amiodarone therapy improves the success rate after catheter ablation of persistent atrial fibrillation during long-term follow-up. This might be due to a decreased incidence of early arrhythmia recurrences after catheter ablation of atrial fibrillation and an improved reverse remodelling process.

Catheter ablation of persistent atrial fibrillation : Circumferential pulmonary vein ablation: beneficial effect of an additional linear lesion at the roof of the left atrium on the long-term outcome.

BACKGROUND: Circumferential pulmonary vein ablation is still the standard approach in patients with persistent atrial fibrillation. However, the results are not very favourable and more complex ablation strategies are the subject of current controversy. Therefore, we have evaluated the effect of an additional linear lesion at the roof of the left atrium on the long-term outcome. METHODS: A total of 125 patients with symptomatic persistent atrial fibrillation underwent a circumferential pulmonary vein ablation procedure in combination with an additional linear lesion at the roof of the left atrium (group A). The long-term follow-up data was compared to 125 patients with similar clinical characteristics who underwent circumferential pulmonary vein ablation without an additional linear lesion at the roof of the left atrium (group B). RESULTS: The ablation procedure could be performed as planned in all 250 patients. Three years after catheter ablation, the success rate was 72.0% (no arrhythmia recurrence in 90 out of 125 patients) in group A and 63.2% in group B (no arrhythmia recurrence in 79 out of 125 patients; P = 0.04). There were no major complications. CONCLUSIONS: Catheter ablation of persistent atrial fibrillation comprising a circumferential pulmonary vein ablation and an additional linear lesion at the roof of the left atrium provides more favourable long-term results than circumferential pulmonary vein ablation alone.

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.

Catheter ablation of paroxysmal atrial fibrillation: circumferential pulmonary vein ablation: success rates with and without exclusion of areas adjacent to the esophagus.

BACKGROUND: Catheter ablation has become the first line of therapy in patients with symptomatic, recurrent, drug-refractory paroxysmal atrial fibrillation. Circumferential pulmonary vein ablation is still the standard approach in these patients. The occurrence of an atrioesophageal fistula is a rare but life-threatening complication after such ablation procedures. This is due to the fact that the esophagus does frequently have a very close anatomical relationship to the left or right pulmonary vein ostia. The aim of our study was to evaluate whether the exclusion of areas adjacent to the esophagus does have a significant effect on the success rate after circumferential pulmonary vein ablation. METHODS: Two hundred consecutive patients [121 men, 69 women; mean age 59.1 years (SD ± 11.3 years)] with symptomatic paroxysmal atrial fibrillation underwent a circumferential pulmonary vein ablation procedure (using the CARTO- or the NAVX-system). In 100 patients, a complete circumferential pulmonary vein ablation was attempted regardless of the anatomical relationship between the ablation sites and the esophagus (group A). In the remaining 100 patients, the esophagus was marked by a special EP catheter and areas adjacent to the esophagus were excluded from the ablation procedure. After discharge, patients were scheduled for repeated visits at the arrhythmia clinic at 1, 3, 6, 9, 12, 24 and 36 months after the ablation procedure. RESULTS: The ablation procedure could be performed as planned in all 200 patients. In group A, all pulmonary veins could be isolated successfully in 88 out of 100 patients (88%). A mean number of 3.9 pulmonary veins (SD ± 0.37 PVs) were isolated per patient. The 12 cases of an incomplete pulmonary vein isolation were due to poorly accessible pulmonary vein ostia. In group B, all pulmonary veins could be isolated successfully in only 58 out of 100 patients (58%; P < 0.01). A mean number of 3.5 PVs (SD ± 0.6 PVs) were isolated per patient (P < 0.01). This was mostly due to a close anatomical relationship to the esophagus. The ablation strategy had to be modified in 46/100 patients in group B because of a close anatomical relationship between the right (n = 25) or left (n = 21) pulmonary vein ostia and the esophagus. One year after the ablation procedure, 87% of patients in group A (87/100) and 79% of patients in group B (79/100) were free from an arrhythmia recurrence (P = 0.19). Three years after catheter ablation, the success rate was 80% (no arrhythmia recurrence in 80 out of 100 patients) in group A and 66% in group B (no arrhythmia recurrence in 66 out of 100 patients; P = 0.04). There were no major complications during long-term follow-up. CONCLUSIONS: The exclusion of areas adjacent to the esophagus results in a markedly higher percentage of incompletely isolated pulmonary veins after circumferential pulmonary vein ablation procedures. This results in a significantly higher arrhythmia recurrence rate during long-term follow-up.

Catheter ablation of persistent atrial fibrillation : Long-term results of circumferential pulmonary vein ablation in combination with a linear lesion at the roof of the left atrium.

BACKGROUND: Catheter ablation has become the first line of therapy in patients with symptomatic, recurrent, drug-refractory atrial fibrillation. However, catheter ablation of persistent atrial fibrillation is still a challenge. Various relatively complex ablation strategies exist and their results are not very favorable. Therefore, the aim of our study was to evaluate a well-defined reasonable approach to catheter ablation of persistent atrial fibrillation. The strategy consisted of a circumferential pulmonary vein ablation in combination with a linear lesion at the roof of the left atrium. METHODS: A total of 150 patients with symptomatic persistent atrial fibrillation were enrolled in this study. All patients underwent catheter ablation of persistent atrial fibrillation using the abovementioned approach. RESULTS: The ablation procedure could be performed as planned in all 150 patients. Five years after catheter ablation, the success rate was 71.3% (no arrhythmia recurrence in 107 out of 150 patients). There were no major complications during long-term follow-up. CONCLUSION: Catheter ablation of persistent atrial fibrillation can be performed safely and effectively using this ablation strategy providing favorable long-term follow-up results.

Radiofrequency catheter ablation for redo procedures after pulmonary vein isolation with the cryoballoon technique : Long-term outcome.

BACKGROUND: Catheter ablation has become the first line of therapy in patients with symptomatic, recurrent, drug-refractory atrial fibrillation (AF). Cryoablation has been shown to be a safe and effective technique for pulmonary vein (PV) isolation. However, the arrhythmia recurrence rate is high after cryoablation procedures. Radiofrequency catheter ablation has been shown to be an effective strategy for redo procedures in these patients and to provide a favourable outcome during midterm follow-up. The aim of this study was to analyse whether the strategy also provides favourable results during long-term follow-up (5 years). METHODS: In this study 30 patients (paroxysmal AF: 22 patients, persistent AF: 8 patients) underwent a redo procedure after initially successful circumferential PV isolation with the cryoballoon technique (Arctic Front Balloon, Medtronic). The redo ablation procedures were performed using a segmental approach or a circumferential ablation strategy (CARTO; Biosense Webster, Diamond Bar, CA, USA) depending on the intraprocedural findings. RESULTS: During the repeat procedure, a mean number of 2.9 reconnected PV (SD ± 1.0) were detected. In 20 patients, a segmental approach was sufficient to eliminate the residual PV conduction because only a few PV fibres were recovered (1-3 reconnected PV; group A). In the remaining 10 patients, a circumferential ablation strategy was used because of a complete recovery of the pulmonary vein - left atrial (PV-LA) conduction (group B). All reconnected PV were isolated successfully again. A third or fourth ablation procedure had to be performed in 4 (3 and 1, respectively) patients (13.3%). At 5­year follow-up, 66.7% of all patients were free from an arrhythmia recurrence (20 out of 30). There were no major complications during long-term follow-up. CONCLUSION: In patients with an initial circumferential PV isolation using the cryoballoon technique, a repeat ablation procedure can be safely and effectively performed using radiofrequency catheter ablation providing good long-term follow-up results.

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.

Efficacy of cut-and-sew box isolation of the posterior left atrium for treatment of atrial fibrillation-long-term follow-up after a modified maze procedure.

BACKGROUND: Box isolation of the posterior left atrium is one surgical or catheter ablative approach for treating atrial fibrillation (AF). In such cases, incomplete transmurality or recovery of pulmonary vein conduction after the application of various ablative techniques is considered the main reason for the recurrence of postprocedural arrhythmia. The use of solely cut-and-sew box isolation does not have these disadvantages and therefore demonstrates maximum efficacy for this therapeutic approach. METHODS: We treated 15 patients with both an indication for open heart surgery and AF (2 paroxysmal, 6 short persistent [<12 months], and 7 long persistent [>12 months] cases) with a solely cut-and-sew box lesion. These patients were then retrospectively followed up over the long term with respect to the end point of freedom of atrial tachyarrhythmias >30 seconds. RESULTS: The median follow-up duration was 42 months (range, 32-84 months). Five (63%) of 8 patients with preoperative paroxysmal or short persistent AF had no arrhythmia recurrence, whereas arrhythmia recurrence was documented in all 7 patients with preoperative long persistent AF. CONCLUSIONS: Despite reliable transmural isolation with cut-and-sew lesions, we observed long-term arrhythmia recurrence in patients who had preoperative paroxysmal or short persistent AF, suggesting that therapy approaches that are more complex than box isolation might be needed for selected patients to achieve long-term stable sinus rhythm, despite the initially paroxysmal or short persistent character of the arrhythmia. A high rate of recurrence in patients with severe structural heart disease and preoperative long persistent AF might indicate that, in general, isolation of the left posterior atrium alone is not an adequate therapeutic approach for these patients.

Catheter ablation of persistent atrial fibrillation: anatomically based circumferential pulmonary vein ablation in combination with a potential-guided segmental approach to achieve complete pulmonary vein isolation.

BACKGROUND: Catheter ablation has become the first line of therapy in patients with symptomatic, recurrent, drug-refractory atrial fibrillation. However, catheter ablation of persistent atrial fibrillation is still a challenge. Various rather complex ablation strategies exist and their results are not very favorable. Therefore, the aim of our study was to evaluate a well-defined reasonable approach to catheter ablation of persistent atrial fibrillation. The strategy consisted of a circumferential pulmonary vein ablation in combination with a potential-guided segmental approach to achieve complete pulmonary vein isolation and a linear lesion at the roof of the left atrium. METHODS: A total of 43 patients (30 men, 13 women; mean age 55 years (SD ± 9 years)) with symptomatic persistent atrial fibrillation were enrolled in this study. All patients underwent catheter ablation of persistent atrial fibrillation using the above-mentioned approach (with the CARTO or the NAVX system). Additionally, catheter ablation of the mitral isthmus and the right atrial isthmus was performed in selected cases. In all patients, cardiac MRI or multi-detector spiral computed tomography was performed prior to the ablation procedure and a surface rendered model of the left atrium was created. After discharge, patients were scheduled for repeated visits at the arrhythmia clinic at 1, 3, 6, 9, and 12 months after the ablation procedure. RESULTS: The ablation procedure could be performed as planned in all 43 patients. Nine patients had to undergo a repeat ablation procedure, so that a total of 52 procedures were evaluated. An additional linear lesion was created at the mitral isthmus in three patients (7%) during the initial procedure and in one patient (2.3%) during the second procedure. Catheter ablation of the right atrial isthmus was performed in 11 patients (25.6%) during the first procedure and in four additional patients during the redo procedure (9.3%). Twenty-four out of 43 patients (55.8%) experienced an arrhythmia recurrence within the first 3 months after ablation requiring an electrical cardioversion. At 1-year follow-up, analysis of a 7-day Holter monitoring revealed no evidence for an arrhythmia recurrence in 26 of 43 patients (60.5%). In nine of 43 patients (20.9%), only short episodes of paroxysmal atrial fibrillation were documented. In eight patients (18.6%), a recurrence of persistent atrial fibrillation (>48 h) was revealed by the long-term recordings. A duration of persistent atrial fibrillation >3 months was the most powerful predictor for arrhythmia recurrences at 1-year follow-up. A subgroup analysis revealed a markedly higher rate of stable sinus rhythm at 1-year follow-up in patients with a short duration of atrial fibrillation (≤ 3 months) compared to patients with a longer duration of AF (>3 months) prior to the procedure (72.0% versus 44.4%). There were no major complications. CONCLUSIONS: Catheter ablation of persistent atrial fibrillation can be performed safely and effectively using this ablation strategy (especially in patients with short-lasting persistent atrial fibrillation (≤ 3 months)).

Atorvastatin treatment affects atrial ion currents and their tachycardia-induced remodeling in rabbits.

AIMS: Atrial fibrillation (AF) leads to electrical atrial remodeling including alterations of various ion channels early after arrhythmia onset. The beneficial effects of statins in AF treatment due to their influence on oxidative stress and inflammation are discussed. Our hypothesis was that statins might also alter atrial ion currents and their early tachycardia-induced remodeling. MAIN METHODS: Effects of an atorvastatin treatment (7 days) on atrial ion currents and their tachycardia-induced alterations were studied in a rabbit model of tachycardia-induced electrical remodeling (rapid atrial pacing (600 min) for 24 and 120 h). Ion currents (L-type calcium channel [I(Ca,L)], transient outward current [I(to)]) were measured using whole cell patch clamp method and were compared with previous experiments in untreated but also tachypaced animals. KEY FINDINGS: Atorvastatin treatment alone decreased I(Ca,L) similar to rapid atrial pacing alone, currents were also further reduced by additional atrial tachypacing. I(to) and its pacing-induced down-regulation after 24 h were not influenced by atorvastatin treatment. However, I(to) was still reduced after 120 h in atorvastatin-treated animals and did not return to control values as expected. SIGNIFICANCE: The present study establishes that an atorvastatin treatment can affect atrial ion currents and their tachycardia-induced remodeling in a rabbit model. These results show that-amongst other positive effects on oxidative stress and inflammation-the impact of statins on ion currents and their tachycardia-induced alterations might also play a role in "upstream" treatment of AF with HMG-CoA reductase inhibitors.

Effects of selective mineralocorticoid receptor antagonism on atrial ion currents and early ionic tachycardia-induced electrical remodelling in rabbits.

Over the past years, the importance of the renin-angiotensin-aldosterone system in atrial fibrillation (AF) pathophysiology has been recognised. Lately, the role of aldosterone in AF pathophysiology and mineralocorticoid receptor (MR) antagonism in "upstream" AF treatment is discussed. Hypothesising that selective MR antagonism might also influence atrial ion currents (L-type calcium current [I (Ca,L)], transient outward potassium current [I (to)], sustained outward potassium current [I (sus)]) and their tachycardia-induced remodelling, the effects of an eplerenone treatment were studied in a rabbit model. Six groups each with four animals were built. Animals of the control group received atrial pacing leads, but in contrast to the pacing groups, no atrial tachypacing (600 per minute for 24 and 120 h immediately before heart removal) was applied. Animals of the eplerenone groups were instrumented/paced as the corresponding control/pacing groups, but were additionally treated with eplerenone (7 days before heart removal). Atrial tachypacing was associated with a reduction of I (Ca,L). I (to) was decreased after 24 h of tachypacing, but returned to control values after 120 h. In the absence of rapid atrial pacing, MR antagonism reduced I (Ca,L) to a similar extent as 120 h of tachypacing alone. Based on this lower "take-off level", I (Ca,L) was not further decreased by high-rate pacing. I (to) and its expected tachycardia-induced alterations were not influenced by MR antagonism. In our experiments, selective MR antagonism influenced atrial I (Ca,L) and its tachycardia-induced alterations. As changes of I (Ca,L) are closely linked with atrial calcium signalling, the relevance of these alterations in AF pathophysiology and, accordingly, AF treatment is likely and has to be further evaluated.

Catheter ablation of ventricular tachycardias in patients with ischemic cardiomyopathy: validation of voltage mapping criteria for substrate modification by myocardial viability assessment using FDG PET.

BACKGROUND: Catheter ablation is of growing importance in patients with an ischemic cardiomyopathy and recurrent episodes of ventricular tachyarrhythmias. Most ablation strategies in these patients are based on the detection of areas of scar and border zones to normal myocardium. However, the mapping criteria for identifying these areas have not been validated sufficiently so far. Therefore, we have performed a comparison between electroanatomical bipolar voltage maps obtained during substrate-based VT ablation procedures and [18 F]fluoro-2-deoxyglucose PET studies performed prior to these procedures. METHODS: Seven patients suffering from severe coronary artery disease and repetitive ventricular tachycardias were enrolled in this study. In all patients, there was a history of myocardial infarction and the left ventricular function was severely impaired. A FDG PET was performed at least 1 day prior to the ablation procedure in all patients. Then, a substrate-based VT ablation procedure was performed using the CARTO system (Biosense Webster, Diamond Bar, CA, USA). Finally, the FDG PET images and the bipolar voltage maps were compared in all patients. RESULTS: The ablation procedures could be performed successfully in all patients and 1-5 monomorphic VTs could be eliminated in each patient. There were no major complications. At 1-year follow-up, five out of seven patients (71.4%) remained free from any arrhythmia recurrence. In all patients, there were extensive areas of scar and adjacent low-voltage areas could be identified in the CARTO bipolar voltage maps. In areas commonly defined as "dense scar" (bipolar voltage amplitude <0.5 mV), the mean FDG uptake was 43.1% (SD ±18.2%) indicating predominantly scar tissue. In the so-called low-voltage border zones the mean FDG uptake ranged between 49.5% [(SD ±15.8%); >0.5-1 mV] and 60.1% [(SD ±14.8%); >1-1.5 mV], thereby indicating the presence of predominantly viable myocardium. In areas with a bipolar voltage amplitude >1.5 mV the presence of viable myocardium was confirmed by a mean FDG uptake of approximately 60%. CONCLUSIONS: The results of our study demonstrate that there is a significant amount of viable myocardium in the low-voltage border zones of scars frequently targeted as ablation sites. Therefore, RF current delivery in these areas should be restricted to the minimum assumed to be necessary for successful catheter ablation because extensive RF applications might result in a further deterioration of the left ventricular function. Larger studies are needed to validate our results and to develop more reliable criteria for distinguishing areas of scar from viable myocardium in CARTO bipolar voltage maps.

Atrial fibrosis and atrial fibrillation: the role of the TGF-ß1 signaling pathway.

BACKGROUND: Atrial fibrosis concurs with chronic atrial fibrillation (AF), a phenomenon that contributes to the resistance to restore and maintain sinus rhythm (SR). Fibrogenesis represents a complex process in which the transforming growth factor-ß1 (TGF-ß1) pathway may play a major role, e.g. in the setting of myocardial infarction. The present study addresses the potential contribution of the TGF-ß1 signaling pathway to atrial fibrosis in patients with AF. METHODS AND RESULTS: Right atrial appendages of 163 patients were excised during heart surgery and grouped according to rhythm (SR vs. AF) and AF duration. Five groups were defined: SR, paroxysmal/chronic persistent AF (<6 months), chronic permanent AF (CAF) of 7-24 months, 25-60 months, and >60 months duration. Collagen content of atria, determined morphometrically, revealed a steady and significant increase in patients with SR (14.6±8.9%) up to patients with CAF of >60 months (28.1±7.1%). Likewise, expression of TGF-ß1 mRNA and protein, TGF-ß-receptor-II protein, profibrotic phospho-Smad-2 and -4 proteins increased. However, the TGF-ß(1) effect appeared to decline with increasing AF duration, characterized by a decrease in TGF-ß-receptor-I protein, increases of TGF-ß inhibiting Smad-7 protein and a reduction of ph-Smad-2. CONCLUSIONS: Human atrial fibrogenesis in patients with atrial fibrillation is accompanied by a biphasic response, an early increase and later loss of responsiveness to TGF-ß(1). It appears that fibrosis progresses despite compensatory changes in the TGF-ß-signaling pathway. The sequential changes in the contribution of different profibrotic processes during the establishment of AF may offer the opportunity to selectively interfere with the atrial remodeling process at different stages.

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.

Assessing acute ventricular volume changes by intracardiac impedance in a chronic heart failure animal model.

BACKGROUND: Implantable device diagnostics may play an essential role in simplifying the care of heart failure patients by providing fundamental insights into their complex clinical patterns. Early recognition of heart failure progression by a continuous hemodynamic monitoring would allow for timely therapeutic interventions to prevent decompensation and hospitalization. In this study, the feasibility of assessing ventricular volume changes by implant-based measurements of intracardiac impedance was tested in a heart failure animal model. METHODS: Heart failure was induced in five minipigs by high-rate pacing over 3 weeks. During a final open-chest examination a graded dobutamine stress test was performed. Stroke volume (SV) was measured by an ultrasonic flow probe at the ascending aorta. End diastolic pressure (EDP) and maximum pressure slope (dP/dtmax) were calculated from a left ventricular microtip catheter signal. Impedance was measured by an implanted pacemaker between biventricular leads. Stroke impedance (SZ) was calculated as the difference between end-systolic and end-diastolic impedance (EDZ). RESULTS: Administration of dobutamine led to an increase in SV (55+/-16%), dP/dtmax (107+/-89%), and SZ (56+/-30%). EDP changed by 37+/-21% whereas EDZ changed by 7.4+/-4%. Significant correlations were found between SZ and SV (r=0.88), and between EDZ and EDP (r=-0.82). CONCLUSION: The strong correlation with SV allows the application of intracardiac impedance measurements for an implant-based continuous monitoring of cardiac function. Impedance may also be used for hemodynamic optimization of cardiac resynchronization therapy.

[How useful are the algorithms for the differential diagnosis of the monomorphic tachycardias with broad QRS complex in cardiac emergencies?]. / Wie nützlich sind die Algorithmen zur Differentialdiagnostik der monomorphen Tachykardien mit breitem QRS-Komplex in kardiologischen Notfällen?

This review gives an integrated summary of the three old and two new ECG algorithms for the differential diagnosis of monomorphic regular tachycardias with broad QRS complex. Several studies have provided evidence that a ventricular tachycardia was diagnosed correctly by doctors on call and emergency physicians only in 35-50% of cases. Whether an algorithm may really improve diagnosis in everyday clinical practice and whether the algorithms are feasible for physicians, has not yet been clarified.The algorithms possess a high sensitivity of 88-95%, but only a satisfactory specificity of 73-80%. The values of all algorithms are similar. In the hands of physicians with little experience, the incidence of correct diagnoses is likely to be markedly lower. The algorithms have considerable limitations, especially with regard to the application of the "morphology criteria". As the nondetection of a ventricular tachycardia can have fatal consequences for the patient, any tachycardia with broad QRS complex should be treated as ventricular tachycardia in emergencies. In hemodynamically stable patients, the administration of adenosine for diagnostic purposes should immediately lead to a correct diagnosis. Based on the study situation, a schematic representation for the differential diagnosis has been created which follows very simple ECG criteria identifiable by any physician.

Catheter ablation of atrial fibrillation using the Navx-/Ensite-system and a CT-/MRI-guided approach.

BACKGROUND: Catheter ablation has become the first line of therapy in patients with symptomatic, recurrent, drug refractory atrial fibrillation. However, catheter ablation of atrial fibrillation is still a challenge. This is partially due to the high degree of variability with regard to the individual anatomy. Nevertheless, 3D imaging systems (CT, MRI) provide detailed information about the individual left atrial and pulmonary vein morphology. A 3D CT or MRI reconstruction of the left atrium can be displayed in the Navx-/Ensite-system in a synchronised way during the ablation procedure, thereby facilitating the intervention. This study summarizes our preliminary experience with different strategies of AF ablation using the Navx-/Ensite-system and a CT-/MRI-guided approach. METHODS: In a total of 41 patients, cardiac MRI (n = 7) or multi-detector spiral computed tomography (n = 34) was performed prior to an ablation procedure. Catheter ablation was performed for paroxysmal atrial fibrillation in 31 patients and for persistent atrial fibrillation in 10 patients. A 3D MRI or high resolution spiral CT data acquisition was performed and a surface rendered model of the LA was created. This model was displayed in the Navx-/Ensite-system throughout the ablation procedure. RESULTS: Catheter ablation was performed using the Navx-system (n = 38) or the Ensite-system (n = 3). Three strategies were used depending on the type of atrial fibrillation: segmental isolation of the pulmonary veins (facilitated by a 3D real-time visualization of the ablation catheter and a circumferential mapping catheter; group A: 20 patients), linear lesions (group C: 3 patients) and a combined approach (group B; 18 patients). The CT-/MRI-models provided an excellent overview over the pulmonary veins and the left atrial appendage. They revealed a high degree of variability with regard to the individual anatomy (e.g. dimensions of the left atrial appendage, pulmonary vein ostia). The CT scans provided a more detailed reconstruction of the left atrial anatomy than the MRI scans (especially in patients who were in atrial fibrillation at the time of the data acquisition). In some patients, the CT-/MRI-models revealed a very small diameter of some pulmonary veins or side branches close to the ostium (e.g. right inferior pulmonary vein). Therefore, no attempt was made to achieve complete pulmonary vein isolation in some patients. In group A, 16/20 (80%) patients had no arrhythmia recurrence [mean follow-up 359 days (SD +/- 317 days)]. Twelve out of eighteen (67%) patients in group B [mean follow-up 452 days (SD +/- 311 days)] and 2/3 (67%) patients in group C did not experience an arrhythmia recurrence [mean follow-up 1,000 days (SD +/- 34 days)]. There were no major complications. CONCLUSIONS: The information derived from 3D CT- or MRI-reconstructions facilitates AF ablations performed with the Navx-/Ensite-mapping system and enhances the safety of these procedures. Furthermore, the availability of an additional impedance-based 3D real-time visualization of the ablation catheter and the circular mapping catheter placed in the pulmonary veins represents a major advantage of the Navx system.

Segmental pulmonary vein ablation: success rates with and without exclusion of areas adjacent to the esophagus.

BACKGROUND: Catheter ablation has become the first line of therapy in patients with symptomatic recurrent, drug-refractory atrial fibrillation (AF). The occurrence of an atrioesophageal fistula is a rare but serious complication after AF-ablation procedures. This risk is even present during segmental pulmonary vein (PV) ablation procedures because the esophagus does frequently have a very close anatomical relationship to the right or left PV ostia. The aim of the present study was to analyze whether the exclusion of areas adjacent to the esophagus does have a significant effect on the success rates after segmental pulmonary vein ablation procedures. METHODS: Forty-three consecutive patients with symptomatic paroxysmal AF were enrolled in this study. In all patients, a segmental PV ablation procedure was performed. The procedures were facilitated by a 3D real-time visualization of the circumferential mapping catheter placed in the pulmonary veins using the NavX system (St. Jude Medical, St. Paul, MN, USA; open irrigated tip ablation catheter; 43 degrees C; 30 W). In 21 patients, a complete ostial PV isolation was attempted regardless of the anatomical relationship between the ablation sites and the esophagus (group A). In the remaining 22 patients, the esophagus was marked by a stomach tube and areas adjacent to the esophagus were excluded from the ablation procedure (group B). After discharge, patients were scheduled for repeated visits at the arrhythmia clinic at 1, 3, and 6 months after the ablation procedure. RESULTS: The segmental pulmonary vein ablation procedure could be performed as planned in all patients. In group A, all pulmonary veins could be isolated successfully in 14 out of 21 patients (67%). A mean number of 3.7 pulmonary veins (SD +/- 0.5 PVs) were isolated per patient. The main reasons for an incomplete PV isolation were: small diameter of the PVs, side branches close to the ostium, or poorly accessible PV ostia. In group B, all PVs could be isolated successfully in only 12 out of 22 patients (55%; P = 0.54). A mean number of 3.2 PVs (SD +/- 0.9 PVs) were isolated per patient (P = 0.05). This was mostly due to a close anatomical relationship to the esophagus. The ablation strategy had to be modified in 16/22 patients in group B because of a close anatomical relationship between the left (n = 10) or right (n = 6) PV ostia and the esophagus. After 3 months, the percentage of patients free from an AF recurrence was not significantly different between the two groups (90% vs 95%; P = 0.61). After 6 months, there was no significant difference between the success rates either (81% vs 82%; P = 1.0). There were no major complications in both groups. CONCLUSIONS: The exclusion of areas adjacent to the esophagus results in a moderately higher percentage of incompletely isolated PVs. However, it does not have a significant effect on the AF recurrence rate during short-term and mid-term follow-up.