Publications by authors named "Jürgen Biermann"

19 Publications

  • Page 1 of 1

Two siblings with early repolarization syndrome: clinical and genetic characterization by whole-exome sequencing.

Europace 2020 Dec 16. Epub 2020 Dec 16.

Department of Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Heart Center, Amsterdam, The Netherlands.

Aims : The early repolarization syndrome (ERS) can cause ventricular fibrillation (VF) and sudden death in young, otherwise healthy individuals. There are limited data suggesting that ERS might be heritable. The aim of this study was to characterize the clinical phenotype and to identify a causal variant in an affected family using an exome-sequencing approach.

Methods And Results : Early repolarization syndrome was diagnosed according to the recently proposed Shanghai ERS Score. After sequencing of known ERS candidate genes, whole-exome sequencing (WES) was performed. The index patient (23 years, female) showed a dynamic inferolateral early repolarization (ER) pattern and electrical storm with intractable VF. Isoproterenol enabled successful termination of electrical storm with no recurrence on hydroquinidine therapy during 33 months of follow-up. The index patient's brother (25 years) had a persistent inferior ER pattern with malignant features and a history of syncope. Both parents were asymptomatic and showed no ER pattern. While there was no pathogenic variant in candidate genes, WES detected a novel missense variant affecting a highly conserved residue (p. H2245R) in the ANK3 gene encoding Ankyrin-G in the two siblings and the father.

Conclusion : We identified two siblings with a malignant ERS phenotype sharing a novel ANK3 variant. A potentially pathogenic role of the novel ANK3 variant is suggested by the direct interaction of Ankyrin-G with the cardiac sodium channel, however, more patients with ANK3 variants and ERS would be required to establish ANK3 as novel ERS susceptibility gene. Our study provides additional evidence that ERS might be a heritable condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/europace/euaa357DOI Listing
December 2020

Cognitive behavioural therapy for insomnia does not appear to have a substantial impact on early markers of cardiovascular disease: A preliminary randomized controlled trial.

J Sleep Res 2020 10 28;29(5):e13102. Epub 2020 Jun 28.

Department of Psychiatry and Psychotherapy, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany.

According to the World Health Organization, cardiovascular diseases are the leading cause of death in the world. Therefore, early prevention of these diseases is a public health priority. Epidemiological data suggest that insomnia may be a modifiable risk factor for cardiovascular diseases. A randomized controlled trial in a sample of insomnia patients without cardiovascular disease was conducted to investigate the effects of insomnia treatment on early markers of cardiovascular diseases assessed by 24-hr ambulatory blood pressure, heart rate and heart rate variability monitoring, and morning fasting blood samples. Forty-six patients with insomnia disorder were randomized to cognitive behavioural therapy for insomnia (CBT-I; n = 23) or a waitlist control condition (n = 23). Contrary to the hypothesis, intention-to-treat analyses did not show any significant treatment effects on early markers of cardiovascular disease (d = 0.0-0.6) despite successful insomnia treatment (d = 1.3). Potential methodological and conceptual reasons for these negative findings are discussed. Future studies might include larger sample sizes that are at risk of cardiovascular diseases and focus on other cardiovascular markers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jsr.13102DOI Listing
October 2020

Variable Presentations and Ablation Sites for Manifest Nodoventricular/Nodofascicular Fibers.

Circ Arrhythm Electrophysiol 2019 09 11;12(9):e007337. Epub 2019 Sep 11.

Cardiology Division (T.E.W., B.K.L., E.P.G., M.M.S.), University of California San Francisco.

Background: Nodofascicular and nodoventricular (NFV) accessory pathways connect the atrioventricular node and the Purkinje system or ventricular myocardium, respectively. Concealed NFV pathways participate as the retrograde limb of supraventricular tachycardia (SVT). Manifest NFV pathways can comprise the anterograde limb of wide-complex SVT but are quite rare. The purpose of this report is to highlight the electrophysiological properties and sites of ablation for manifest NFV pathways.

Methods: Eight patients underwent electrophysiology studies for wide-complex tachycardia (3), for narrow-complex tachycardia (1), and preexcitation (4).

Results: NFV was an integral part of the SVT circuit in 3 patients. Cases 1 to 2 were wide-complex tachycardia because of manifest NFV SVT. Case 3 was a bidirectional NFV that conducted retrograde during concealed NFV SVT and anterograde causing preexcitation during atrial pacing. NFV was a bystander during atrioventricular node re-entrant tachycardia, atrial fibrillation, atrial flutter, and orthodromic atrioventricular re-entrant tachycardia in 4 cases and caused only preexcitation in 1. Successful NFV ablation was achieved empirically in the slow pathway region in 1 case. In 5 cases, the ventricular insertion was mapped to the slow pathway region (2 cases) or septal right ventricle (3 cases). The NFV was not mapped in cases 5 and 7 because of its bystander role. QRS morphology of preexcitation predicted the right ventricle insertion sites in 4 of the 5 cases in which it was mapped. During follow-up, 1 patient noted recurrent palpitations but no documented SVT.

Conclusions: Manifest NFV may be critical for wide-complex tachycardia/manifest NFV SVT, act as the retrograde limb for narrow-complex tachycardia/concealed NFV SVT, or cause bystander preexcitation. Ablation should initially target the slow pathway region, with mapping of the right ventricle insertion site if slow pathway ablation is not successful. The QRS morphology of maximal preexcitation may be helpful in predicting successful right ventricle ablation site.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCEP.119.007337DOI Listing
September 2019

Fascicular parasystole and recurrent syncope - a case report.

Eur Heart J Case Rep 2018 Mar 5;2(1):yty020. Epub 2018 Mar 5.

Department of Cardiology and Angiology I, Heart Center Freiburg University, Hugstetter Str. 55, 79106 Freiburg, Germany.

Introduction: Parasystole refers to an ectopic pacemaker that discharges with a constant rate competing with the primary pacemaker of the heart the sinus node. Parasystolic pacemakers have been described in the atrium, atrioventricular node, His bundle, and in the ventricle. Ventricular parasystole usually carries a benign prognosis, but there are a few reports of ventricular tachyarrhythmia initiated by parasystolic beats.

Case Presentation: We present a case of a 15-year-old otherwise healthy teenager with recurrent most likely arrhythmic syncope who was diagnosed with ventricular parasystole from the left posterior fascicle. After exclusion of structural and primary electrical heart disease, the patient was deemed at increased risk of parasystole-induced tachyarrhythmia, and thus catheter ablation of the ectopic focus was performed. Since catheter ablation the patient continues to be free of any symptoms.

Discussion: This report highlights the potential risks of parasystole in context of recurrent syncope and reviews the available literature on parasystole and ventricular tachyarrhythmia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjcr/yty020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426017PMC
March 2018

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

PLoS One 2015 24;10(7):e0131570. Epub 2015 Jul 24.

Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Abteilung für Elektrophysiologie, Faculty of Medicine, Technische Universität München, Munich, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131570PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514854PMC
May 2016

The Diagnosis, Risk Stratification, and Treatment of Brugada Syndrome.

Dtsch Arztebl Int 2015 Jun;112(23):394-401

Department of Cardiology and Angiology I, University Heart Center Freiburg · Bad Krozingen.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3238/arztebl.2015.0394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498009PMC
June 2015

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

Europace 2015 Jun 8;17(6):915-20. Epub 2015 Jan 8.

Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Abteilung für Elektrophysiologie, Faculty of Medicine, Technische Universität München, Munich, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/europace/euu344DOI Listing
June 2015

Electrocardiographic identification of prior myocardial infarction during right ventricular pacing--effect of septal versus apical pacing.

Int J Cardiol 2014 Dec 5;177(3):977-81. Epub 2014 Oct 5.

Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Abteilung für Elektrophysiologie, Faculty of Medicine, Technische Universität München, Munich, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2014.09.187DOI Listing
December 2014

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

Int J Cardiol 2014 Jul 26;174(3):713-20. Epub 2014 Apr 26.

Heart Centre Freiburg University, Department of Cardiology and Angiology I, Freiburg, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2014.04.229DOI Listing
July 2014

Remote ICD-monitoring in detection and follow-up of triggers of idiopathic ventricular fibrillation: implications for the clinical management of IVF patients.

Int J Cardiol 2014 Jun 6;174(2):e29-31. Epub 2014 Apr 6.

Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2014.03.207DOI Listing
June 2014

[Ventricular tachycardia under stress : Characteristic symptom or prognostic relevance?].

Herzschrittmacherther Elektrophysiol 2013 Dec 8;24(4):197-201. Epub 2013 Oct 8.

Klinik für Kardiologie und Angiologie I, Universitäts-Herzzentrum Freiburg - Bad Krozingen, Hugstetter Straße 55, 79106, Freiburg i. Br., Deutschland,

Exercise-induced ventricular tachycardia (EIVT) is typical and quite common in patients with long QT-Syndrome (LQTS) or catecholaminergic polymorphic ventricular tachycardia (CPVT). Although patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) or hypertrophic cardiomyopathy (HCM) experience EIVT infrequently, the occurrence of EIVT is of great prognostic value in these patients. The following overview will introduce these cardiomyopathies and highlight the importance of their EIVT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00399-013-0293-3DOI Listing
December 2013

Intracardiac Echocardiography during Catheter-Based Ablation of Atrial Fibrillation.

Cardiol Res Pract 2012 29;2012:921746. Epub 2012 May 29.

Department of Cardiology and Angiology, University Hospital of Freiburg, Hugstetter Stra β e 55, 79106 Freiburg, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2012/921746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368317PMC
August 2012

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

Cardiol Res Pract 2011 2;2011:615087. Epub 2011 Jul 2.

Department of Cardiology and Angiology, University Hospital Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4061/2011/615087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130977PMC
July 2011

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

J Cardiovasc Pharmacol 2011 Feb;57(2):223-30

Innere Medizin III, Universitätsklinik Freiburg, Freiburg, Germany.

Transgenic rabbits expressing pore mutants of K(V)7.1 display a long QT syndrome 1 (LQT1) phenotype. Recently, NS1643 has been described to increase I(Kr).We hypothesized that NS1643 would shorten the action potential duration (APD(90)) 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 APD(90) 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 I(Kr) augmentation. In conclusion, K(V)11.1 channel activation shortens the cardiac APD in a rabbit model of inherited LQT1, but it comes with the risk of excessive shortening of APD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FJC.0b013e318203a44dDOI Listing
February 2011

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

Eur J Pharmacol 2011 Jan 17;650(1):309-16. Epub 2010 Oct 17.

Department of Cardiology and Angiology, University Hospital of Freiburg, Freiburg, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2010.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997896PMC
January 2011

Acute pulmonary embolism and a patent foramen ovale: analysis of atrial right-to-left shunting by biphasic transcardiopulmonary thermodilution curves.

J Clin Anesth 2010 Aug;22(5):367-9

Department of Cardiology and Angiology, Intensive Care Unit, University Hospital of Freiburg, 79106 Freiburg, Germany.

A 69-year-old woman with an acute pulmonary embolism developed an intracardiac right-to-left shunt, which was diagnosed early on and quantified via biphasic transcardiopulmonary thermodilution curves. With transesophageal echocardiography, a patent foramen ovale and an impressive atrial right-to-left shunt were visualized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jclinane.2009.05.009DOI Listing
August 2010

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

Europace 2010 Aug 13;12(8):1199-200. Epub 2010 May 13.

Medizinische Klinik III, Kardiologie und Angiologie, Universitätsklinikum Freiburg, Hugstetter Str 55, 79106 Freiburg, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/europace/euq121DOI Listing
August 2010

Persistent left superior vena cava: an unusual but conquerable obstacle in device implantation.

Clin Res Cardiol 2009 Apr 13;98(4):268-70. Epub 2009 Feb 13.

Medizinische Universitätsklinik Innere Medizin III, Abt. für Kardiologie und Angiologie, Freiburg im Breisgau, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00392-009-0755-0DOI Listing
April 2009

Characterization of regulatory mechanisms and states of human organic cation transporter 2.

Am J Physiol Cell Physiol 2006 Jun 4;290(6):C1521-31. Epub 2006 Jan 4.

Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Universitätsklinikum Münster, Domagkstrasse 3a, D-48149 Münster, Germany.

Polyspecific organic cation transporters (OCTs) have a large substrate binding pocket with different interaction domains. To determine whether OCT regulation is substrate specific, suitable fluorescent organic cations were selected by comparing their uptake in wild-type (WT) human embryonic kidney (HEK)-293 cells and in HEK-293 cells stably transfected with hOCT2. N-amidino-3,5-diamino-6-chloropyrazine-carboxamide (amiloride) and 4-[4-(dimethylamino)-styryl]-N-methylpyridinium (ASP) showed concentration-dependent uptake in hOCT2 at 37 degrees C. After subtraction of unspecific uptake determined in WT at 37 degrees C or in hOCT2 at 8 degrees C saturable specific uptake of both substrates was measured. Km values of hOCT2-mediated uptake of 95 microM amiloride and 24 microM ASP were calculated. Inhibition of amiloride and ASP uptake by several organic cations was also measured [IC50 (in microM) for amiloride and ASP, respectively, tetraethylammonium (TEA) 98 and 30, cimetidine 14 and 26, and tetrapentylammonium (TPA) 7 and 2]. Amiloride and ASP uptake were significantly reduced by inhibition of Ca2+/CaM complex (-55 +/- 5%, n = 10 and -63 +/- 2%, n = 15, for amiloride and ASP, respectively) and stimulation of PKC (-54 +/- 5%, n = 14, and -31 +/- 6%, n = 26) and PKA (-16 +/- 5%, n = 16, and -18 +/- 4%, n = 40), and they were increased by inhibition of phosphatidylinositol 3-kinase (+28 +/- 6%, n = 8, and +55 +/- 17%, n = 16). Inhibition of Ca2+/CaM complex resulted in a significant decrease of Vmax (160-99 photons/s) that can be explained in part by a reduction of the membrane-associated hOCT2 (-22 +/- 6%, n = 9) as determined using FACScan flow cytometry. The data indicate that saturable transport by hOCT2 can be measured by the fluorescent substrates amiloride and ASP and that transport activity for both substrates is regulated similarly. Inhibition of the Ca2+/CaM complex causes changes in transport capacity via hOCT2 trafficking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpcell.00622.2005DOI Listing
June 2006