Silent cerebral lesions (SCL) have been identified on brain magnetic resonance imaging (MRI) in apparently asymptomatic patients after cardiovascular procedures. After atrial fibrillation (AF) ablation incidences range from 1 to over 40% depending upon different factors. MRI definition should include diffusion weighted imaging (DWI) to detect hyperintensities (bright spots) due to acute brain ischemia correlated with a hypointensity in the apparent diffusion coefficient mapping (ADC-map) to rule out artifacts. The genesis of SCL appears to be multifactorial and appears to be a result of embolic events either from gaseous or solid particles. The MRI pattern appears to be comparable not hinting towards a specific mechanism. One may distinguish two different MRI definition: one, more sensitive, for silent ischemic events (SCE) not proven to be related to cell death (DWI positive but FLAIR negative); and one for SCL that are due to edema caused by cell death which will lead to glial cell scar formation (DWI positive and FLAIR positive). For ease of data interpretation, future studies should ensure both definitions, and that DWI and FLAIR data is acquired using identical slice thickness and orientation. Risk factors associated with increased SCL-incidences involve patient-specific, technology-associated and procedural determinants. When using a high-sensitive MRI definition differences in SCE-rates in between technologies appear to be less prominent. Further studies on the effects of different periprocedural anticoagulation regimen, different steps of the ablation procedure and new technologies are needed. For now, SCL incidence may determine the thrombogenic potential of an ablation technology and further studies to reduce or avoid SCL generation are desirable. It appears reasonable, that any SCE should be avoided.

Catheter ablation of atrial fibrillation (AF) has been increasingly used to treat symptomatic patients. Within the last years a growing interest in ablation of persistent AF forms has evolved. Factors that may influence outcome of these procedures to treat persistent AF may be patient-specific (pre-procedural), procedure-related or may involve different post-ablation follow-up strategies. In this review potential factors predicting recurrence of AF after ablation of persistent AF have been evaluated. In essence, data is limited mostly due to incongruent definitions of persistent AF. Left atrial dimensions, duration of continuous AF and AF cycle length may be patient-specific predictors of outcome. Intra-procedural parameters involved in recurrence prediction may be extent of ablation (effective pulmonary vein isolation appears mandatory) and termination of AF during ablation. Timing and number of cardioversion if persistent AF recurs may predict outcome, as well. Many studies have identified strators for higher recurrence rates in rather small patient groups and need to be further evaluated in larger patient collectives. www.jafib.com 8 Feb-Mar, 2012 | Vol 4 | Issue 5 has been proposed in different studies. Success rates differ widely depending on patient selection, experience of the operators and follow-up. Also, persistent AF is poorly defined by 1. either AF lasting longer than 7 days or 2. AF undergoing conversion by either drugs or electrical cardioversion. This definition may include a wide variety of patients with different stages of AF disease and therefore, success rates may vary widely.1 14 Recurrences after ablation of persistent AF may include recurrent AF or atrial tachycardia either due to inconsistent left atrial lesions, reconnected pulmonary veins (PVs) or as tachycardia originating from previously not ablated areas of the right and left atrium. So far, only a limited number of studies have looked into predictors of AF recurrence after ablation of persistent AF. It can be speculated that 1. pre-procedural markers indicating ablation failure may exist, 2. intra-procedural determinants of failure and 3. post-procedural predictors of poorer outcome may be identified. It is most likely, that there is not a single predictor but a combination of different factors influencing outcome in this inhomogeneous patient group. As always with multivariate prediction analysis the number of determinants included in such a model will have effects on outcome of these statistical methods. In addition, many factors are correlated with each other in a rather complex way and may therefore not be appropriately analyzed using simple statistical methodology. In different studies, persistent AF has been identified as a significant confounder for a 50 to 55% higher risk for recurrence mostly in univariate analysis. This can be explained by the assumption, that a persistent type of AF includes many confounding variables that may lead to different results in multivariate analyses. Again, different stages of atrial disease may affect success rates of ablation procedures.15 21 1. Pre-Procedural Factors Many variables that may affect outcome of ablation procedures for AF have been evaluated mostly in either paroxysmal AF patients or in a mixed population. Only a limited number of studies evaluated the effect of pre-procedural variables in a predefined subgroup including only patients with persistent AF.18-21 1.1. Left Atrial Dimensions Left atrial dilation is often associated with AF and vice-versa. Patients with large left atrial dimensions may have substantial left atrial myopathy serving as a basis for the perpetuation of AF. Left atrial dilation results in anisotropic conduction and regional differences in refractory periods. The combination of electrical and substrate remodelling facilitates the onset and perpetuation of AF. Left atrial dimensions are usually evaluated using pre-procedural transthoracic echocardiography and measurements may differ widely intraindividually and in between observers. Left atrial volume as a more concise parameter has so far not been consistently evaluated in ablation studies. Left atrial size was found to be a major determinant for recurrence of ablation for persistent AF in 2 studies. Freedom from AF decreases with increasing left atrial size up to 46mm but no change is identified in patients > 46mm left atrial dimensions 7. In a second study by Lo et al.37 left atrial size was greater in patients with failure of persistent AF ablation. As a cut-off value left atrial diameter > 43mm significantly influences 1and 2-year AF free survival rates (54% at 1 year, 51% at 2 years compared to 91% for 1 and 2 year AF free survival in patients with left atrial diameters < 43mm).7, 37 In contrast, a large cohort analysis by Bhargava et al.19 and a second study by Wokhlu et al. did not find left atrial size to be predictive of single procedure AF ablation success in persistent AF. These studies appeared to include mostly patients with shorter duration persistent AF which may explain some of the discrepancies. Overall data is controversial and this may in some part be due to the insufficiency of echocardiographic measurement of correct left atrial dimensions in addition to differences in ablation strategies in different study groups. It can be concluded though, that increasing left atrial size may negatively affect rhythm success after ablation of persistent AF but no clear 2-dimensional cut-off value exists that may definitely predict failure of the ablation procedure. Journal of Atrial Fibrillation Featured Review www.jafib.com 9 Feb-Mar, 2012 | Vol 4 | Issue 5 1.2. Duration of Persistent AF Data on duration of persistent AF prior to ablation is inconclusive. Bhargava et al.19 identified a longer duration of persistent AF as predictor of failure after a single ablation procedure (hazard ratio 1.74; p=0.003). A recent study by Rostock et al.7 documented duration of persistent AF longer than 6 months to be an independent predictor for AF recurrence in persistent AF ablation. McCready et al.18 did not identify AF duration as predictive for recurrence of AF (hazard ratio 1.07; p=0.11) in the overall group of persistent AF. In the group of patients with a left atrial diameter above 43mm, duration of AF appeared as an independent predictor of AF recurrence. Specifically, patients with long-lasting persistent AF have poorer outcome after ablation emphasizing the importance of duration of AF prior to ablation. There does not appear to be a clear cut-off value for continuous AF duration indicating a relevant drop-down in efficacy (apart from 1 year consistent AF as indicated in the definition of long-lasting persistent AF). It needs to be stressed that pre-ablation AF duration in persistent AF cases should include only the time consistently in AF. In many centres, extent of ablation strategy is mainly based on duration of persistent AF prior to the ablation making multivariate analysis statistically challenging. It can be concluded though, that long persistence of AF (> 6 months prior to ablation) negatively influences recurrence of AF after ablation. Again no clear cut-off value exists and ablation may be extended to additional areas in these patients. 1.3. Hypertension Hypertensive heart disease is a major risk factor for the incidence of AF. In mixed populations with different types of AF hypertension appears to be a significant predictor of AF recurrence after ablation. 3 studies have evaluated hypertension as a strator of ablation outcome in persistent AF ablation in a multivariate model. Whereas hypertension was a predictor of ablation failure in patients with persistent AF in the study by Bhargava et al.19 and for very late recurrence in the study by Wilber et al. (personal communication at Boston AF symposium 2011), it was not a relevant factor in the study by McCready et al.18 Data remains inconclusive on the predictive role of hypertension on persistent AF ablation outcome. 1.4. Structural Heart Disease/Left Ventricular Function/Congestive Heart Failure The presence of structural heart disease (mostly coronary artery disease) may affect AF ablation outcome. In addition, recent publications have highlighted the role of AF ablation in patients with left ventricular dysfunction or congestive heart failure. The prognostic relevance of underlying ventricular abnormalities on outcome of ablation strategies has not been clearly elucidated. One can speculate though, that severely impaired left ventricular function may lead to more aggressive ablation strategies to terminate AF. Most studies evaluating structural or valvular heart disease as a predictor did not identify a relevant relation to ablation outcome but 2 studies indicated a significant association in a mixed AF population. In a homogenous group of persistent AF, 2 studies documented contrary findings in relation to AF recurrence and structural heart disease/cardiomyopathy, Whereas McCready et al.18 did not find any relation in 191 patients. Rostock et al.17 identified a prognostic relevance of congestive heart failure in a multivariate regression analysis in 395 patients. Congestive heart failure involved a 10-fold risk for AF recurrence after the index procedure and after the final procedure. The existence of coronary artery disease also predicted a negative outcome after the final procedure in this study. Congestive heart failure appears to be an independent predictor of AF recurrence in patients with persistent AF as indicated in a single study on nearly 400 patients undergoing ablation in a center with high expertise. 1.5. Age and Sex A recently published study by Rostock et al.17 indicates a higher recurrence rate in female patients after ablation of persistent AF. A second study by Wilber et al. (personal communication at Boston AF symposium 2011) on 1404 patients with persistent or long-standing persistent AF also documented female gender t

An electrical storm (ES) is defined as multiple ventricular arrhythmia episodes leading to implantable cardioverter defibrillator interventions. Although conventional rhythm stabilization might be of help acutely, ES involves high mortality and morbidity. We evaluated the effect of catheter ablation strategies in the setting of an interhospital collaborative network on the recurrence of ventricular arrhythmia episodes and mortality in patients with ES. Consecutive patients presenting for invasive treatment of ES from December 2007 to December 2009 were included. All patients underwent catheter ablation of ventricular arrhythmia. The strategies were adapted to the individual cardiac pathologic features. The follow-up examination constituted periodic implantable cardioverter defibrillator interrogation. A total of 32 patients were included. Of the 32 patients, 29 (91%) had monomorphic ventricular tachycardia and 3 ventricular fibrillation. The mean number of implantable cardioverter defibrillator-treated episodes within 7 days before ablation was 16 ± 11. Of the 32 patients, 27 underwent ablation within 24 hours after admission, and 5 underwent acute ablation within 8 hours. In 3 patients, epicardial ablation was performed. In all but 2 patients (6%), the clinical arrhythmia was successfully ablated. During a median follow-up of 15 months, 10 patients (31%) had recurrences of sustained ventricular arrhythmia, including 2 patients (6%) with recurrent ES. Three patients (9%) died during the follow-up period. In conclusion, catheter ablation effectively suppressed ventricular arrhythmia midterm recurrences in patients presenting with ES. Catheter ablation is complex in these severely sick patients. The recurrence rate of ventricular arrhythmia appears to be 31% and the mortality rate to be 9%. Collaborative hospital networks to increase the prompt availability of ES ablation might help to optimize the ES outcome.

Background: Biventricular (BiV) is extensively used in the treatment of congestive heart failure but so far no recommendations for optimized programming of atrioventricular-delay (AVD) settings have been proposed. Can AVD optimization be performed using a simple formula based on non-invasive doppler-echocardiography?Methods: 25 patients (ejection fraction 30±8%) received BiV ICDs. Doppler-echocardiographic evaluation of diastolic and systolic flow was performed for different AVDs (30ms to 150ms) and different stimulation sites (left ventricular (LV), right ventricular and BiV). The optimal atrioventricular delay was calculated applying a simple formula based on systolic and diastolic mechanical delays determined during doppler-echocardiography.Results: The mean optimal AVD was calculated to be 112±29ms (50 to 180ms) for BiV, 95±30ms (65 to 150ms) for LV and 75±28ms (40 to 125ms) for right ventricular pacing with wide interindividual variations. Compared to suboptimal AVDs diastolic optimization improved preejection and ejection intervals independent to pacing site. Optimization of the AVD significantly increased ejection time during BiV pacing (279ms versus 266ms; p<0.05). Compared to LV or right ventricular pacing BiV pacing produced the shortest mean pre-ejection and longest ejection intervals as parameters of improved systolic ventricular contractile synchrony. Diastolic filling times were longest during BiV pacing compared to LV or RV pacing.Conclusions: Individual programming of BiV pacing devices increases hemodynamic benefit when implementing the inter-individually widely varying electromechanical delays. Optimization applying a simple formula not only improves diastolic ventricular filling but also increases systolic functional parameters.

Aim: Intravascular ultrasound investigations are new tomographic imaging methods for evaluation of artery dimensions and wall morphology. The present study was performed to test accuracy and observer variability. Method: 3 plastic phantoms and 1 iliacan artery were assessed. The quantitative measurements were made by computerised 3D reconstruction. Results: The plastic phantoms showed ultrasonically three layers of echogenic structures. An intimal fibrous thickening was seen in the iliac artery. The cross sectional diameters were ultrasonically overestimated by 12.6 +/- 5.6%. Due to the lower velocity of sound in water than in blood there were no significant differences to the true diameters. The intra- and interobserved variabilities were determined to 1.4 +/- 0.8% and 2.6 +/- 1.2%. Conclusions: Intravascular ultrasound provides a reproducible method for measuring vessel lumen diameters with excellent intraobserver and interobserver variabilities. For in vitro examinations the different velocities of sound in different media have to be take into account.

Coronary angiograms performed at the time of an acute coronary syndrome typically present vessel occlusions, ruptured plaques or thrombotic lesions that require reperfusion therapy. However, occasionally, no coronary artery stenoses are detected. Myocardial ischemia frequently causes left ventricular wall motion abnormalities that can be seen easily by echocardiography. In our study we aimed to analyze echocardiographic findings in patients with acute coronary syndrome and normal angiogram. After standardized risk stratification, a total of 897 patients were classified as an acute coronary syndrome and underwent a coronary angiography immediately. In 76/897 patients angiography excluded coronary macroangiopathy. Routine echocardiographic assessment in patients with normal angiogram showed in 21.1% a reduced left ventricular systolic function and 32.9% presented with segmental wall motion abnormalities. In summary, by detection of segmental wall motion abnormalities in 1/3 of patients with suspected acute coronary syndrome and normal angiogram, obviously, an echocardiographic evaluation in this patient population is of clinical relevance. Recommendations for performing echocardiography in patients with suspected acute coronary syndromes independent of angiographic findings are strongly supported. Further analyses should implement echocardiographic techniques as contrast and tissue doppler imaging.

Aggressive antithrombotic medical therapy may increase the rate of access-site complications after percutaneous coronary intervention. Frequently, emergency coronary interventions have to be performed in a situation when thrombolysis therapy was administered as the first-line therapeutic approach in acute myocardial infarction but failed to achieve stable conditions.

BackgroundCoronary angiographies performed during acute coronary syndrome show different coronary morphologies—vessel occlusions, thrombi and various types of stenoses. In a few cases of acute coronary syndrome, angiography reveals normal coronary arteries. It is the purpose of this study to analyze this specific subset of patients who presented with an acute coronary syndrome but had a normal coronary angiogram with respect to the preangiographic diagnostics, risk stratification and clinical follow-up.Methods and resultsA total of 897 coronary angiographies were performed as an emergency procedure in our institution. The majority of patients (n=821) presented with coronary artery disease and the majority was treated by mechanical revascularization (86.3%). In 76 patients (8.5%), no coronary artery stenosis was documented. However, according to the preangiographic risk stratification, coronary artery disease was expected in these patients. Observations documented angiographically included coronary spasms (6.6%) and muscle bridges (5.3%). During a mean follow-up of 11.2±6.4 months, one patient developed an acute myocardial infarction requiring coronary intervention. All other patients were free of any cardiac event.ConclusionsIn summary, we have to consider that coronary angiography may not always detect the cause of myocardial ischemia in every patient. There is a small group of patients with normal coronary angiograms during acute coronary syndrome. Additional diagnostic procedures like intravascular ultrasound (IVUS) or the assessment of intracoronary physiological parameters may increase the diagnostic value of angiography.

BACKGROUND AND PURPOSE:Next to noninvasive-recently also invasive-diagnostics, ambulant care in patients with coronary heart disease (CHD) should focus on optimal medication and prevention. The aim of this study was to evaluate actual health care quality concerning drug prescription and preventive care in patients with CHD.PATIENTS AND METHODS:This prospective study was conducted from March 1999 to February 2002 at the University Hospital Bergmannsheil, Bochum, Germany. 300 patients admitted with a suspected CHD and without previous coronary angiography or myocardial infarction were enrolled. Diagnostic and therapeutic regimen complied with actual guidelines. 248 patients (82.7%) including 116 patients with angiographically confirmed CHD were examined after 1 year.RESULTS:On follow-up, only 70.9% of patients with confirmed CHD received a beta-blocker, 83.6% were treated with platelet aggregation inhibitors. Body mass index, portion of overweight patients, and HbA(1c) in patients with diabetes did not change during observation. After 1 year, 48.0% of the subjects had a systolic blood pressure > 139 mmHg, in 22.6% diastolic pressure level was > 89 mmHg. Blood level of low-density cholesterol exceeded the recommended range in 57.0% of the cases observed with equally high portion of inadequately treated patients in the group with confirmed CHD and in the group without CHD.CONCLUSION:Drug therapy, primary and secondary prevention in the observed subjects were fairly poor. Remarkable deficits in health care quality became obvious. There is no lack in availability of evaluated, effective and efficient measures. Thus, physicians' efforts to implement evidence-based guidelines into clinical practice have to be strengthened.

Infantile hemangiomas are endothelial tumors that grow rapidly in the first year of life and regress slowly during early childhood. Although hemangiomas are well-known vascular lesions, little is known about the mechanisms that cause the excessive endothelial cell proliferation in these most common tumors of infancy. To investigate the molecular basis of hemangioma, we isolated endothelial cells from several proliferative-phase lesions and showed that these cells are clonal and exhibit abnormal properties in vitro (E. Boye, Y. Yu, G. Paranya, J. B. Mulliken, B. R. Olsen, J. Bischoff: Clonality and altered behavior of endothelial cells from hemangiomas. J Clin Invest 2001, 107:745–752). Here, we analyzed mRNA expression patterns of genes required for angiogenesis, including members of the vascular endothelial growth factor (VEGF)/VEGF receptor family and the angiopoietin/Tie family, in hemangioma-derived and normal endothelial cells. KDR, Flt-1, Tie1, Tie2, and angiopoietin-2 (Ang2) were strongly expressed in cultured hemangioma-derived endothelial cells and in hemangioma tissue. In contrast, there was little expression of angiopoietin-1 (Ang1) or VEGF. We found Tie2 mRNA and protein up-regulated with a concomitant increase in cellular responsiveness to Ang1 in most hemangioma-derived endothelial cells. Ang2 mRNA was down-regulated in response to serum in hemangioma-derived endothelial cells, but not in normal endothelial cells, suggesting altered regulation. These findings implicate Tie2 and its ligands Ang1 and Ang2 in the pathogenesis of hemangioma.

Während die biventrikuläre Schrittmachertherapie als „Add-on“-Therapie bei der symptomatischen Herzinsuffizienz eingesetzt wird, stellt die medikamentöse Behandlung von symptomatischen, aber auch asymptomatischen Patienten die wesentliche Therapiemöglichkeit dar.

Purpose: Patients with acute coronary syndromes (ACS) should undergo early invasive diagnostic and treatment strategy according to the individual risk stratification. However, in a few cases angiography presents a normal angiogram. Echocardiography in ACS may help to assess the patients' risk and to disclose differential diagnosis in unclear cases. Few data are available on the analysis of echocardiographic findings in a patient population with ACS but normal angiogram. Methods: A total of 51 unselected patients (72.5% male, 53.3 ± 14.5 years) were included between 1999 and 2002. All patients underwent an emergency coronary angiography due to suspected ACS but showed a normal angiogram. Patients underwent echocardiographic examination prior to invasive procedure. Results: The preangiographic risk stratification was as follows: unstable angina (76.5%), elevated troponin T (30%), elevated creatine kinase (24%), electrocardiographic signs of ischemia (60.8%). Thirty‐one patients (60.6%) presented with a normal wall motion. The following regional wall motion abnormalities were seen: septal (n = 4, 7.8%), inferior (n = 9, 17.6%) and anterior (n = 7, 13.7%). A normal ejection fraction was detected in 40 patients (78.4%), a discrete reduction in 8 patients (15.7%), and a relevant reduction in three cases (5.9%). The invasive measurements of the ejection fraction (67 ± 14%) were without any difference to the echocardiographic measurement (68 ± 14%). Conclusions: In spite of a normal angiogram during ACS echocardiography shows regional left ventricular wall motion abnormalities in a relevant number of patients. These findings may influence the need of further diagnostic procedures and perhaps of pharmacological treatment in those patients. Echocardiography should be added to routine diagnostic procedures in patients with ACS.