The effect of BI 409306 on heart rate in healthy volunteers: a randomised, double-blind, placebo-controlled, crossover study.

PURPOSE: The potent, selective phosphodiesterase-9A inhibitor BI 409306 may be beneficial for patients with attenuated psychosis syndrome and could prevent relapse in patients with schizophrenia. Transient BI 409306-dependent increases in heart rate (HR) demonstrated previously necessitated cardiac safety characterisation. We evaluated cardiac effects of BI 409306 in healthy volunteers during rest and exercise. METHODS: In this double-blind, three-way crossover study, volunteers received placebo, BI 409306 50 mg or 200 mg in randomised order (same treatment on Days 1 [resting] and 3 [exercise]). Cardiopulmonary exercise testing was performed twice post treatment on Day 3 of each period. BI 409306-mediated effects on placebo-corrected change from baseline in resting HR (ΔΔHR) were evaluated based on exposure-response analysis and a random coefficient model. Adverse events (AEs) were recorded. RESULTS: Overall, 19/20 volunteers completed. Resting ΔΔHR versus BI 409306 concentration yielded a slope of 0.0029 beats/min/nmol/L. At the geometric mean (gMean) maximum plasma concentration (Cmax) for BI 409306 50 and 200 mg, predicted mean (90% CI) ΔΔHRs were 0.80 (- 0.76, 2.36) and 5.46 (2.44, 8.49) beats/min, respectively. Maximum adjusted mean differences from placebo (90% CI) in resting HR for BI 409306 50 and 200 mg were 3.85 (0.73, 6.97) and 4.93 (1.69, 8.16) beats/min. Maximum differences from placebo in resting HR occurred at/near gMean Cmax and returned to baseline after approximately 4 h. The proportion of volunteers with AEs increased with BI 409306 dose. CONCLUSION: Observed hemodynamic effects following BI 409306 administration were of low amplitude, transient, and followed the pharmacokinetic profile of BI 409306.

Feasibility and effects of a combined adjuvant high-intensity interval/strength training in breast cancer patients: a single-center pilot study.

PURPOSE: To evaluate feasibility of an exercise intervention consisting of high-intensity interval endurance and strength training in breast cancer patients. METHODS: Twenty-six women with nonmetastatic breast cancer were consecutively assigned to the exercise intervention- (n= 15, mean age 51.9 ± 9.8 years) and the control group (n = 11, mean age 56.9 ± 7.0 years). Cardiopulmonary exercise testing that included lactate sampling, one-repetition maximum tests and a HADS-D questionnaire were used to monitor patients both before and after a supervised six weeks period of either combined high-intensity interval endurance and strength training (intervention group, twice a week) or leisure training (control group). RESULTS: Contrarily to the control group, endurance (mean change of VO2, peak 12.0 ± 13.0%) and strength performance (mean change of cumulative load 25.9 ± 11.2%) and quality of life increased in the intervention group. No training-related adverse events were observed. CONCLUSIONS: Our guided exercise intervention could be used effectively for initiation and improvement of performance capacity and quality of life in breast cancer patients in a relatively short time. This might be especially attractive during medical treatment. Long-term effects have to be evaluated in randomized controlled studies also with a longer follow-up. Implications for Rehabilitation High-intensity interval training allows improvement of aerobic capacity within a comparable short time. Standard leisure training in breast cancer patients is rather suitable for the maintenance of performance capacity and quality of life. Guided high-intensity interval training combined with strength training can be used effectively for the improvement of endurance and strength capacity and also quality of life. After exclusion of contraindications, guided adjuvant high-intensity interval training combined with strength training can be safely used in breast cancer patients.

Right ventricular function assessed by tissue Doppler echocardiography in older subjects without evidence for structural cardiac disease.

The aim of our study was to obtain right ventricular (RV) tissue Doppler imaging (TDI) data in older subjects (n = 95, mean age: 74.5 ± 4.6 years) without evidence of hemodynamically significant structural heart disease recruited from a large population-based cohort (ActiFE-Ulm study). Our data indicate that aging may be accompanied by decreasing RV diastolic function and at most little alterations of RV systolic function. Mean values of all parameters were still within the guideline-suggested reference range with most of them closer to the abnormality thresholds. On an individual basis, respective thresholds were also exceeded in some subjects (almost all parameters <20 %) despite the absence of evidence for structural cardiac disease. RV-TDI is a feasible method for evaluation of RV systolic and diastolic function also in a geriatric population as sufficient TDI data was obtainable in the majority of our participants. Published reference values also seem to be mostly suitable although among older subjects, presumed pathological measures might still be compatible with physiological age-related alterations. Therefore, they always have to be interpreted across the clinical context and in relation to other parameters of morphology and function obtained by other ultrasound imaging techniques (M-mode, B-mode, etc.) in the context of echocardiographic evaluation of the right heart.

Accuracy of ECG indices for diagnosis of left ventricular hypertrophy in people >65 years: results from the ActiFE study.

BACKGROUND: The detection of left ventricular hypertrophy (LVH) is still a common objective of electrocardiography (ECG) in clinical practice. AIMS: The aim of our study was to evaluate the accuracy of LVH ECG indices in people older than 65 recruited from a population-based cohort (ActiFE-Ulm study). METHODS: In 432 subjects (mean age 76.2 ± 5.5 years, 51% male), left ventricular mass was echocardiographically determined (Devereux formula) and indexed (LVMI) to body surface area. Several LVH ECG indices (Lewis voltage, Gubner-Ungerleider voltage, Sokolow-Lyon voltage/product, Cornell voltage/product) were calculated with the help of resting ECG data and compared with the echocardiographic assessment. RESULTS: Despite echocardiographic signs of LVH [LVMI > 115 (♂) or >95 g/m2 (♀)] in 47.5% of all subjects, diagnostic performance of all ECG indices was generally low. Magnitude of all LVH-indices was mainly predicted by frontal QRS axis in multivariate linear regression analysis. In comparison with the literature data from younger subjects, average frontal QRS axis turned counterclockwise. DISCUSSION AND CONCLUSIONS: Most probably, age-related counterclockwise turn of frontal QRS axis is mainly explanatory for the decreased magnitude of LVH ECG indices and consecutive worse diagnostic performance of these indices in the elderly. ECG indices for detection of LVH have insufficient predictive values in geriatric subjects and should therefore not be used clinically for this purpose. Nevertheless, due to its established relevancy in cardiac risk stratification in this age group, usage of some established ECG indices might keep its significance even in the age of modern cardiac imaging.

Echocardiographic B-mode evaluation of the right heart in older people: The ActiFE Study.

PURPOSE: Right heart B-mode echocardiography reference values have been predominantly obtained in younger age cohorts (<65years). Aims of the study were to describe and evaluate the feasibility of right heart B-mode echocardiography in a large geriatric cohort and to analyze standard parameters in defined subgroups with or without any evidence for structural cardiac disease. METHODS: ActiFE-Ulm study is a population-based cohort study including a sample of people≥65years old living in the region of Ulm, Germany. Echocardiography including right heart parameters was performed within a cardiovascular follow-up of 688 subjects. PRINCIPAL RESULTS: Non-obtainability of right heart B-mode data was rather not a consequence of accompanying cardiac diseases or risk factors but of a more obese body composition. Mean values of right heart measurements of our subpopulation of subjects without evidence for structural cardiac disease were continuously higher than those of the guidelines (e.g. mean right ventricular end diastolic area 23.5±5.6cm(2) (males), 20.3±5.0cm(2) (females)). On an individual basis, guideline-suggested abnormality thresholds were also often exceeded, whereas this situation occurred more often in male than in female subjects. MAJOR CONCLUSIONS: Methodically, right heart B-mode echocardiography in older subjects is challenging. Our results suggest an ageing-associated right heart enlargement. Utilization of published right heart reference values in older adults seems to be problematic and in clinical practice, they always have to be interpreted within the clinical and functional context and in relation to other right heart echocardiographic parameters.

Concurrent Validity of activPAL and activPAL3 Accelerometers in Older Adults.

The aim of this study was to assess concurrent validity between activPAL and activPAL3 accelerometers in a sample of 53 community-dwelling older adults ≥ 65 years. Physical activity (PA) was measured simultaneously with activPAL and activPAL3 while performing scripted activities. The level of agreement between both devices was calculated for sitting/lying, standing, and walking. In addition, PA was measured over one week using activPAL to estimate the expected agreement with activPAL3 in real life. Overall agreement between activPAL and activPAL3 was 97%. Compared with activPAL, the largest disagreement was seen for standing, with 5% categorized as walking by activPAL3. For walking and sitting/lying, the disagreement was 2%, respectively. The expected daily differences between activPAL3 and activPAL were +15.0 min (95% CI: 11.3-18.8) for walking and +29.5 min (95% CI: 6.2-52.7) for standing. ActivPAL and activPAL3 showed good agreement in older adults. However, if using these devices interchangeably, observed differences might still bias results.

Atrial reverse remodeling: restitution of early tachycardia-induced alterations of atrial ion currents after termination of rapid atrial pacing in rabbits.

BACKGROUND AND PURPOSE: Studies report on the reversal of electrophysiological parameters altered by atrial tachycardia after cessation of the latter. However, there is no data concerning reversal of tachycardia-induced alterations of ion currents. Reverse remodeling of atrial ion currents (I(Ca,L), I(to), I(sus)) was studied in our rabbit model of tachycardia-induced electrical remodeling. METHODS: Three groups each with four animals were built. Rapid atrial pacing (600/min) for 5 days was applied in all groups. Thereafter, different time intervals (5, 10, 20 days) were awaited before the patch clamp experiments. RESULTS: Similar to I(to) remodeling in our model, within 20 days after cessation of atrial tachycardia, time course of I(to) reverse remodeling was also U-shaped. In contrast, there was no significant recovery of I(Ca,L) which was initially reduced by rapid atrial pacing. CONCLUSION: Relevance of a missing recovery of I(Ca,L) is likely as this current is closely linked with intracellular calcium handling.

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.

Effects of dexamethasone and atorvastatin on atrial sodium current and its early tachycardia-induced electrical remodeling in rabbits.

PURPOSE: Atrial fibrillation (AF) results in tachycardia-induced ionic remodeling. Pharmacological prevention of tachycardia-induced ionic remodeling not only with "classical" antiarrhythmics but also with drugs which provide a basis for some of the pillars of the so-called "upstream" therapy of AF like corticosteroids or statins has been proposed as a therapeutic strategy. Amongst other ion currents, atrial sodium current I(Na) and its tachycardia-induced alterations play an important role in AF pathophysiology. Thus, effects of a dexamethasone (DT) and atorvastatin treatment (AT) on atrial sodium current I(Na) and its tachycardia-induced remodeling were studied in a rabbit model. METHODS: 9 groups with 4 animals were examined. Atrial pacemaker leads were implanted in all animals. No rapid atrial pacing (600/min) was performed in the control group but for 24 or 120 hours in the respective pacing groups. Instrumentation and pacing did not differ from the respective drug groups but an additional treatment with dexamethasone or atorvastatin (7 days) was performed. RESULTS: Rapid atrial pacing (RAP, 600/min) reduced I(Na) after 24 hours (≈ -50%) with no further reduction after 120 hours. DT reduced I(Na) (≈ -20%), current densities in consecutively tachypaced animals did not differ from those in untreated animals. AT reduced INa similar as RAP, subsequent RAP did not further diminish I(Na). CONCLUSIONS: Impact of corticosteroids and statins on INa and its tachycardia-induced alterations also contribute to the mode of action of these substances in upstream treatment of atrial fibrillation.

Effects of aldosterone and mineralocorticoid receptor antagonism on cardiac ion channels in the view of upstream therapy of atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia in man. Over the past years, importance of the renin-angiotensin-aldosterone system in AF pathophysiology has been recognized. Lately, the role of aldosterone in AF pathophysiology and mineralocorticoid receptor (MR) antagonism in "upstream" AF treatment is discussed with special regards concerning the effects on AF-induced structural remodeling. However, there is more and more evidence that MR antagonism also influences atrial electrophysiology and, respectively, AF-induced electrical remodeling, whereas the molecular mechanisms are almost unknown. The aim of this mini-review is to give an overview about the role of aldosterone in AF pathophysiology in principle and to summarize current available data concerning affection of cardiac ion channels by aldosterone and MR antagonism. Finally, as modulation of oxidative stress is discussed as one main therapy principle of "upstream" treatment of AF, potential mechanisms how modulation of oxidative stress by aldosterone and accordingly MR antagonism might alter atrial ion currents are delineated. Summarized, publications concerning potential mechanisms of aldosterone- and MR antagonism-modulated cardiac ion channels in various experimental settings are almost exclusively limited to the ventricular level and, partly, they are also contradictorily. Translation of these data to the atria is problematic because atrial and ventricular electrophysiology exhibit remarkable differences. It can be concluded that further research on the "atrial level" is needed in order to clarify the potential impact of the affection of atrial ion channels by aldosterone and accordingly MR antagonism in "upstream" therapy of AF.

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)).

Genetic Polymorphisms as Risk Stratification Tool in Primary Preventive ICD Therapy.

More and more implantable cardioverter-defibrillators (ICDs) are implanted as primary prevention of sudden cardiac death (SCD). However, major problem in practice is to identify high-risk patients for SCD. Different methods for noninvasive risk stratification do not have a sufficient positive or negative predictive value. Since current approaches lead to implantation of ICDs in a large number of patients who will never suffer an arrhythmic event and simultaneously patients still die of SCD who currently did not seem eligible for primary preventive ICD implantation, there is a need for additional tools for risk stratification. Epidemiological studies point to a hereditary risk of SCD. Different susceptibility of each person concerning arrhythmogenic events might be explained by genetic polymorphisms. By obtaining an individual "pattern" of polymorphisms of genes encoding for proteins which are important in arrhythmogenesis in one patient, risk stratification in primary prevention of SCD might by improved.

Influence of dexamethasone on atrial ion currents and their early ionic tachycardia-induced electrical remodeling in rabbits.

BACKGROUND: Certain evidence points to a role of inflammation in AF pathophysiology. Thus, antiinflammatory treatment of AF is discussed. Effects of a dexamethasone treatment (7 days) on atrial ion currents (I(Ca,L), I(to), I(sus)) and their tachycardia-induced remodeling were studied in a rabbit model. METHODS: 6 groups of 4 animals each were built. Rapid atrial pacing (600 min) was performed for 24 and 120 hours with/ without dexamethasone treatment. Ion currents were measured using whole cell patch clamp method. RESULTS: Rapid atrial pacing reduced (I(Ca,L), I(to) was decreased after 24 hours but almost returned to control values after 120 hours. When dexamethasone-treated animals also underwent atrial tachypacing, pacing-induced reduction of I(Ca,L) was still observed after 24 hours and was even augmented after 120 hours compared to untreated but tachypaced animals. I(to) was not influenced by dexamethasone alone. In dexamethasone-treated animals, reduction of I(to) was not observed after 24 hours but occurred after 120 hours of atrial tachypacing. I(sus) was neither influenced by rapid atrial pacing nor by dexamethasone. Biophysical properties of all currents were affected neither by rapid atrial pacing nor by dexamethasone. CONCLUSION: Dexamethasone influenced tachycardia-induced alterations of atrial I(to). Our experiments give evidence that - amongst other anti-inflammatory action - impact of dexamethasone on ion currents and their tachycardia-induced alterations might also play a role in treatment/prevention of AF with steroids.

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.

Alcohol-induced electrical remodeling: effects of sustained short-term ethanol infusion on ion currents in rabbit atrium.

BACKGROUND: In some patients, above-average alcohol consumption before occurrence of atrial fibrillation (AF) in terms of a "holiday heart syndrome" (HHS) can be determined. There is evidence that long before development of apparent alcohol-induced cardiomyopathy, above-average alcohol consumption generates an arrhythmogenic substrate which abets the onset of AF. Changes of atrial current densities in terms of an electrical remodeling after sustained short-term ethanol infusion in rabbits as a potential part of HHS pathophysiology were examined in this study. METHODS: Rabbits of the ethanol group (EG) received sustained short-term intravenous alcohol infusion for 120 hours (during infusion period, blood alcohol level did not fall below 158 mg/dl), whereas NaCl 0.9% was infused in the placebo group (PG). Using patch clamp technique in whole-cell mode, atrial current densities were measured and compared between both groups. RESULTS: Ethanol infusion did not alter current densities of I(to) [58.7 +/- 5.0 pA/pF (PG, n = 20 cells) vs. 53.9 +/- 5.0 pA/pF (EG, n = 24)], I(sus) [11.3 +/- 1.4 pA/pF (PG, n = 20) vs. 10.2 +/- 1.0 pA/pF (EG, n = 24)], and I(K1) [-1.6 +/- 0.3 pA/pF (PG, n = 17) vs. -2.0 +/- 0.3 pA/pF (EG, n = 22)]. However, alcohol infusion resulted in a remarkable reduction of I(Ca,L) current densities [-28.4 +/- 1.8 pA/pF (PG, n = 20) vs. -15.2 +/- 1.4 pA/pF (EG, n = 22)] and I(Na) [-75.4 +/- 3.6 pA/pF (PG, n = 17) vs. -35.4 +/- 4.4 pA/pF (EG, n = 21)], respectively. CONCLUSION: Sustained short-term ethanol infusion in rabbits alters atrial current densities. HHS might be favored by alcohol-induced atrial electrical remodeling.

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.