Jürgen Biermann

Early Heparin Administration Reduces Risk for Left Atrial Thrombus Formation during Atrial Fibrillation Ablation Procedures

Objective. Despite the use of anticoagulation during left atrial (LA) ablation procedures, ischemic cerebrovascular accidents (CVAs) are recognized as a serious complication. Heparin is usually given after safe transseptal access has been obtained, resulting in a short unprotected dwell time of catheters within the LA, which may account for CVAs. We investigated the frequency of CVAs and LA thrombus formation as detected by intracardiac ultrasound (ICE) depending on the timing of heparin administration. Methods and Results. Sixty LA ablation procedures with the use of ICE were performed in 55 patients. Patients were grouped by heparin administration after (Group I, n = 13) and before (Group II, n = 47) transseptal access. Group I patients were younger (56.6 ± 13.7 versus 65.9 ± 9.9 years, P = .01); other clinical and echocardiographic characteristics did not differ between groups. Early thrombus formation was observed in 2 (15.4%) of group I patients as compared to 0% of group II patients (P = .04). One CVA (2.1%) occurred in one group II patient without prior thrombus detection, and none occurred in group I patients (P = ns). Conclusion. Early administration of heparin reduces the risk of early intracardiac thrombus formation during LA ablation procedures. This did not result in reduced rate of CVAs.

Pharmacological activation of Kv11.1 in transgenic long QT-1 rabbits.

Transgenic rabbits expressing pore mutants of KV7.1 display a long QT syndrome 1 (LQT1) phenotype. Recently, NS1643 has been described to increase IKr. We hypothesized that NS1643 would shorten the action potential duration (APD90) in LQT1 rabbits. Transgenic LQT1 rabbits were compared with littermate control (LMC) rabbits. In vivo electrocardiogram studies in sedated animals were performed at baseline and during 45 minutes of intravenous infusion of NS1643 or vehicle in a crossover design. Ex vivo monophasic action potentials were recorded from Langendorff-perfused hearts at baseline and during 45-minute perfusion with NS1643. Left ventricular refractory periods were assessed before and after NS1643 infusion. Genotype differences in APD accommodation were also addressed. In vivo NS1643 shortened the QTc significantly in LQT1 compared with vehicle. In Langendorff experiments, NS1643 significantly shortened the APD90 in LQT1 and LMC [32.0 ± 4.3 milliseconds (ms); 21.0 ± 5.0 ms] and left ventricular refractory periods (23.7 ± 8.3; 22.6 ± 9.9 ms). NS1643 significantly decreased dp/dt (LQT1: 49% ± 3%; LMC: 63% ± 4%) and increased the incidence of arrhythmia. The time course of APD adaptation was impaired in LQT1 rabbits and unaffected by IKr augmentation. In conclusion, KV11.1 channel activation shortens the cardiac APD in a rabbit model of inherited LQT1, but it comes with the risk of excessive shortening of APD.

Intracardiac Echocardiography during Catheter-Based Ablation of Atrial Fibrillation

Accurate delineation of the variable left atrial anatomy is of utmost importance during anatomically based ablation procedures for atrial fibrillation targeting the pulmonary veins and possibly other structures of the atria. Intracardiac echocardiography allows real-time visualisation of the left atrium and adjacent structures and thus facilitates precise guidance of catheter-based ablation of atrial fibrillation. In patients with abnormal anatomy of the atria and/or the interatrial septum, intracardiac ultrasound might be especially valuable to guide transseptal access. Software algorithms like CARTOSound (Biosense Webster, Diamond Bar, USA) offer the opportunity to reconstruct multiple two-dimensional ultrasound fans generated by intracardiac echocardiography to a three-dimensional object which can be merged to a computed tomography or magnetic resonance imaging reconstruction of the left atrium. Intracardiac ultrasound reduces dwell time of catheters in the left atrium, fluoroscopy, and procedural time and is invaluable concerning early identification of potential adverse events. The application of intracardiac echocardiography has the great capability to improve success rates of catheter-based ablation procedures.

ICD Shock, Not Ventricular Fibrillation, Causes Elevation of High Sensitive Troponin T after Defibrillation Threshold Testing—The Prospective, Randomized, Multicentre TropShock-Trial

Background The placement of an implantable cardioverter defibrillator (ICD) has become routine practice to protect high risk patients from sudden cardiac death. However, implantation-related myocardial micro-damage and its relation to different implantation strategies are poorly characterized. Methods A total of 194 ICD recipients (64±12 years, 83% male, 95% primary prevention of sudden cardiac death, 35% cardiac resynchronization therapy) were randomly assigned to one of three implantation strategies: (1) ICD implantation without any defibrillation threshold (DFT) testing, (2) estimation of the DFT without arrhythmia induction (modified “upper limit of vulnerability (ULV) testing”) or (3) traditional safety margin testing including ventricular arrhythmia induction. High-sensitive Troponin T (hsTnT) levels were determined prior to the implantation and 6 hours after. Results All three groups showed a postoperative increase of hsTnT. The mean delta was 0.031±0.032 ng/ml for patients without DFT testing, 0.080±0.067 ng/ml for the modified ULV-testing and 0.064±0.056 ng/ml for patients with traditional safety margin testing. Delta hsTnT was significantly larger in both of the groups with intraoperative ICD testing compared to the non-testing strategy (p≤0.001 each). There was no statistical difference in delta hsTnT between the two groups with intraoperative ICD testing (p = 0.179). Conclusion High-sensitive Troponin T release during ICD implantation is significantly higher in patients with intraoperative ICD testing using shock applications compared to those without testing. Shock applications, with or without arrhythmia induction, did not result in a significantly different delta hsTnT. Hence, the ICD shock itself and not ventricular fibrillation seems to cause myocardial micro-damage. Trial Registration ClinicalTrials.gov NCT01230086

Safety of mid-septal electrode placement in implantable cardioverter defibrillator recipients — Results of the SPICE (Septal Positioning of ventricular ICD Electrodes) study

BACKGROUND Detrimental effects of right ventricular (RV) apical pacing have directed the interest toward alternative pacing sites such as the RV mid-septum. As safety data are scarce for implantable cardioverter defibrillator (ICD) recipients the study aims to evaluate ICD lead performance in the mid-septal position. METHODS AND RESULTS A total of 299 ICD recipients (79% male, aged 65.2 ± 12.1 years, 83% primary prevention of sudden cardiac death) were randomized to receive the RV ICD electrode either in a mid-septal (n=145) or apical (n=154) location. Event-free survival was evaluated at 3 (primary endpoint) and 12 months (secondary endpoint). Events included a composite of lead revision, suboptimal right ventricular electrode performance (including defibrillation thresholds (DFT)>25 J) or lead position not in accordance with randomized location. Event-free survival at 3 (12) months was observed in 80.6% (72.3%) of patients randomized to a mid-septal and in 82.2% (72.1%) of patients randomized to an apical lead position, p=0.726 (p=0.969). Pre-defined margins for non-inferiority were not reached at 3 or 12 months. High DFT was found in 7 patients (5.0%) of the mid-septal and in 3 (2.2%) patients of the apical group (p=0.209). CONCLUSION In ICD recipients electrode positioning to the RV mid-septum or the RV apex results in slightly different rates concerning the survival free of lead revision, suboptimal right ventricular electrode performance or non-randomized lead position. Non-inferiority of the mid-septal lead location cannot be concluded. This should be taken into consideration when a mid-septal lead position is pursued. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov identifier NCT00745745.

Nicorandil normalizes prolonged repolarisation in the first transgenic rabbit model with Long-QT syndrome 1 both in vitro and in vivo

Transgenic rabbits expressing loss-of-function pore mutants of the human gene KCNQ1 (K(v)LQT1-Y315S) have a Long QT-Syndrome 1 (LQT1) phenotype. We evaluated for the first time the effect of nicorandil, an opener of ATP-sensitive potassium channels, and of isoproterenol on cardiac action potential duration and heart rate dependent dispersion of repolarisation in transgenic LQT1 rabbits. In vivo LQT1 and littermate control were subjected to transvenous electrophysiological studies; in vitro monophasic action potentials were recorded from explanted Langendorff-perfused hearts. In vivo ventricular effective refractory periods (VERP) at the right ventricular base were significantly prolonged in LQT1 as compared to littermate control, resulting in a more pronounced VERP dispersion in LQT1. This difference in VERP dispersion between LQT1 and littermate control disappeared after infusion of nicorandil. In vitro, mean action potential durations (APD(75) and APD(90)) of LQT1 were significantly prolonged compared to littermate control at baseline. Nicorandil decreased APD(75) and APD(90) in LQT1 and littermate control at all stimulated heart rates. After adding nicorandil, the APD(90) at all hearts rates and the APD(75) at high heart rates were no longer different. Dispersion of repolarisation (∆APD(75) and ∆APD(90)) was heart rate dependently decreased after nicorandil at all tested stimulation cycle lengths only in LQT1. We demonstrated phenotypic differences of LQT1 and littermate control in vivo and in vitro. Nicorandil 20μmol/l improved repolarisation abnormalities and heterogeneities in transgenic LQT1 rabbits.

The Diagnosis, Risk Stratification, and Treatment of Brugada Syndrome

BACKGROUND Brugada syndrome (BrS) is among the more common familial arrhythmia syndromes, with an estimated prevalence of 1 to 5 per 10 000 persons. It is characterized by a right ventricular conduction delay, dynamic or persistent ST-segment elevations in the precordial leads V1-3 , and an elevated risk of syncope and sudden cardiac death in young adults without structural heart disease. METHODS This article is based on original and review articles on BrS that appeared in English from 2010 onward and were retrieved by a selective search in PubMed, with special attention to international consensus publications on inherited arrhythmogenic diseases. RESULTS According to the new diagnostic criteria, the diagnosis of BrS requires typical ECG changes in only one precordial lead. This will likely increase sensitivity, but may also lead to an increase in asymptomatic patients. Established risk markers include sudden cardiac arrest and a spontaneous type 1 ECG with arrhythmic syncope. Patients with these findings benefit from the implantation of a cardioverter-defibrillator. There is no validated algorithm for risk stratification of asymptomatic patients. Because of the low prevalence of BrS, there have been no randomized controlled trials (RCTs) in this disease, and all recommendations are based on expert opinion. BrS is usually inherited in an autosomal dominant manner. Recently discovered gene polymorphisms modify the risk of BrS, challenging the conception of BrS as a monogenetic disease. Electro-anatomic mapping studies have revealed, for the first time, an arrhythmogenic substrate over the right ventricular outflow tract in BrS patients. CONCLUSION BrS is one important differential diagnosis to consider in patients presenting with syncope or sudden cardiac arrest. The goal of current research is to achieve a deeper understanding of the genetic and electrophysiological changes underlying BrS. Further insights in these areas will probably enable better risk stratification of asymptomatic BrS patients in the future.

A stepwise electrocardiographic algorithm for differentiation of mid-septal vs. apical right ventricular lead positioning: the SPICE ECG substudy

AIMS Right ventricular (RV) septum is a non-apical site targeted during lead implantation. Electrocardiographic (ECG) recognition of mid-septal lead location is challenging. The aim of the study is to determine ECG correlates of RV mid-septal pacing. METHODS AND RESULTS The present study is a pre-specified analysis of a prospective, multicenter study, which randomized recipients of an implantable cardioverter defibrillator to an apical vs. mid-septal RV lead positioning. Following implantation, a 12-lead ECG was recorded during intrinsic rhythm and RV pacing. In total, 227 patients, 121 in the apical group (76.9% males, 67.1 ± 11.3 years) and 106 in the mid-septal group (82.1% males, age 64.7 ± 12.7 years) were included. Apically as compared with septally paced patients had significantly longer paced QRS duration (177.0 ± 25.0 vs. 170.4 ± 21.7, respectively, P = 0.03) and significantly more leftward paced QRS axis (-71.6 ± 33.3° vs. 9.4 ± 86.5°, respectively, P < 0.001). A significantly higher proportion of patients in the mid-septal as compared with the apical group displayed predominantly positive QRS in lead V6 (62.3 vs. 4.1%, P < 0.001), predominantly positive QRS in any of the inferior leads (53.8 vs. 4.1%, P < 0.001), and a QR pattern in lead aVL (53.3 vs. 3.3%, P < 0.001). These ECG correlates were incorporated in a stepwise algorithm with total sensitivity of 87% and specificity of 90% for the identification of a mid-septal lead location. CONCLUSION A mid-septal lead location may be identified using a simple stepwise algorithm, based on the presence of positive QRS in lead V6, positive QRS in any of the inferior leads, and a QR pattern in lead aVL.

Incidental finding of a pulmonary embolus by intracardiac echocardiography during an atrial fibrillation ablation procedure

A 71-year-old female patient was referred for catheter ablation of drug-refractory, symptomatic atrial fibrillation. Initial intracardiac echocardiography (ICE) incidentally showed a mobile embolus stuck at a bifurcation of the right pulmonary artery. The procedure was suspended and the finding was subsequently confirmed by computed tomography pulmonary angiography. This case illustrates a potential value of real-time imaging by ICE during invasive procedures.

Electrocardiographic identification of prior myocardial infarction during right ventricular pacing — Effect of septal versus apical pacing

BACKGROUND Electrocardiographic (ECG) identification of prior myocardial infarction (MI) during right ventricular (RV) pacing is of clinical importance. Proposed ECG criteria have been evaluated only during apical pacing. We evaluated the effect of pacing site on the predictive performance of ECG signs of prior MI. METHODS The present study is a secondary analysis of a prospective, multicenter study which randomized recipients of an implantable cardioverter defibrillator to an apical versus septal RV lead positioning. ECGs of patients with or without prior MI were analyzed for the presence of the following criteria: Cabrera sign, Chapman sign, QR pattern in leads I, aVL, V5 or V6, QR in inferior leads and notching in the descending slope of the QRS complex in inferior leads. RESULTS The MI group included 89 patients (55.1% apically paced), while 99 patients had no prior MI (50.5% apically paced). In the total population, the Cabrera sign presented the highest specificity (97%) and diagnostic accuracy (62.2%), with a sensitivity of 23.6%. The Cabrera sign was the only significant predictor of a prior MI [OR=9.9, (95%CI:2.8-34.5), p<0.001], among all ECG markers. Pacing site did not significantly influence the sensitivity and specificity of the Cabrera sign for detection of prior MI. CONCLUSIONS In our study, the Cabrera sign was the only ECG marker that predicted the presence of prior MI during ventricular paced rhythm. Septal RV lead positioning did not affect the predictive performance of the Cabrera sign.