Thorsten Lewalter

Publications of Thorsten Lewalter

• Adverse effects of permanent atrial fibrillation on heart failure in patients with preserved left ventricular function and chronic right apical pacing for complete heart block.

  Authors: Brigitte Lampe, Christoph Hammerstingl, Jörg Otto Schwab, Fritz Mellert, Birgit Stoffel-Wagner, Andreas Grigull, Rolf Fimmers, Bernhard Maisch, Georg Nickenig, Thorsten Lewalter, Alexander Yang

  Clinical research in cardiology : official journal of the German Cardiac Society. 05/2012;

  BACKGROUND: The impact of atrial fibrillation (AF) on heart failure (HF) was evaluated in patients with preserved left ventricular (LV) function and long-term right ventricular (RV) pacing forBACKGROUND: The impact of atrial fibrillation (AF) on heart failure (HF) was evaluated in patients with preserved left ventricular (LV) function and long-term right ventricular (RV) pacing for complete heart block. METHODS: Clinical, echocardiographic, and laboratory parameters of HF were assessed in 35 patients with established AF who had undergone ablation of the atrioventricular node and pacemaker implantation (Group A) and 31 patients who received dual-chamber pacing for spontaneous complete heart block (Group B). RESULTS: During a follow-up period of 12.7 ± 7.5 years, New York Heart Association (NYHA) functional class increased from 1.3 ± 0.5 to 2.1 ± 0.6 (p < 0.0001) in Group A, and from 1.3 ± 0.4 to 1.6 ± 0.7 (p < 0.01) in Group B. Left ventricular ejection fraction (LVEF) decreased from 59.7 ± 5.1 to 53.0 ± 8.2 (p < 0.0001) in Group A, but remained stable (58.6 ± 4.2 vs. 56.9 ± 7.0 %, p = 0,21) in Group B. At the end of follow-up, markers of LV function were moderately depressed in Group A compared with those in Group B: NYHA class 2.1 ± 0.6 versus 1.6 ± 0.7, p = 0.001; LVEF 53.0 ± 8.2 versus 56.9 ± 7.0 %, p < 0.05; LV diastolic diameter 53.6 ± 5.8 mm versus 50.7 ± 4.9 mm, p < 0.05; N-terminal pro-brain natriuretic peptide (NT-proBNP) 1116.8 ± 883.9 versus 622.9 ± 1059.4 pg/ml, p < 0.05. Progression of paroxysmal AF to permanent AF during follow-up was common, while new onset of AF was rare. Permanent AF was an independent predictor of declining LVEF >10 %, increasing NYHA class ≥1, and NT-proBNP levels >1,000 pg/ml. CONCLUSIONS: Permanent AF was associated with adverse effects on LV function and symptoms of HF in patients with long-term RV pacing for complete heart block, and appears to play an important role in the development of HF in this specific patient cohort.

• Cardiomyopathy Caused by Longterm Treatment with Chloroquine: A Rare Disease, or a Rare Diagnosis?

  Authors: Ernst Tönnesmann, Ingo Stroehmann, Reinhard Kandolf, Hartwig Wolburg, Katharina Strach, Frank Musshoff, Klaus Tiemann, Thorsten Lewalter

  The Journal of rheumatology. 05/2012; 39(5):1099-1103.

• "Largest Amplitude Ablation" is the Optimal Approach for Typical Atrial Flutter Ablation:: A Subanalysis from the AURUM 8 Study.

  Authors: Thorsten Lewalter, Lars Lickfett, Christian Weiss, Christian Mewis, Sebastian Spencker, Werner Jung, Wilhelm Haverkamp, Harald Schwacke, Thomas Deneke, Jochen Proff, Uwe Dorwarth, Wolfgang Bauer

  Journal of cardiovascular electrophysiology. 03/2012;

  Voltage-Guided Cavotricuspid Isthmus Ablation. Introduction: The recently proposed "maximum voltage-guided" (MVG) technique for radiofrequency catheter ablation of atrial flutter targets high-voltageVoltage-Guided Cavotricuspid Isthmus Ablation. Introduction: The recently proposed "maximum voltage-guided" (MVG) technique for radiofrequency catheter ablation of atrial flutter targets high-voltage electrograms along cavotricuspid isthmus (CTI) to ablate the functionally important anatomic muscle bundles alone, without drawing a complete anatomic line across the CTI. This innovative approach may shorten ablation time and procedure duration. Methods and Results: Within the multicenter AURUM 8 study, which compared 8-mm gold- and Pt-Ir-tip catheters in atrial flutter ablation, we made a post hoc comparison of procedural data from 72 patients treated with MVG technique with data from 281 patients undergoing anatomic CTI ablation (unmatched) and with data from 72 patients selected from among those 281 patients such that they were matched with the MVG group with respect to selected baseline parameters and catheter type (matched). The MVG technique markedly reduced (P < 0.001) ablation time (mean 6.9 minutes vs 10.9/9.7 minutes [unmatched/matched]), number of lesions (8.3 vs 13.7/12.9), fluoroscopy time (9.5 minutes vs 20.6/17.9 minutes), procedure duration (59 minutes vs 93/86 minutes), and energy delivered (19 kJ vs 34/30 kJ) compared with anatomic CTI ablation. The incidence of charring was higher for MVG than for anatomic ablation technique (31.9% vs 18.5/15.3%, P < 0.05), where Pt-Ir tip catheters were 6-fold more susceptible to charring than gold-tip catheters (P < 0.001), likely because of a lower thermal conductivity of the Pt-Ir material. The acute success rate was slightly better for MVG than for anatomic ablation technique (97.2% vs 92.2/91.7%, P = n.s.). Conclusion: Major procedural parameters are remarkably improved with MVG technique. Gold-tip catheters are substantially less susceptible to charring and may therefore be preferred over Pt-Ir-tip catheters for MVG ablation technique. (J Cardiovasc Electrophysiol, Vol. pp. 1-7).

• Twenty years of interventional cardiac electrophysiology: Meeting future challenges with continuing innovations.

  Authors: Sanjeev Saksena, Thorsten Lewalter, Berndt Luderitz

  Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing. 06/2011; 31(1):1-2.

• Gold vs. platinum-iridium tip catheter for cavotricuspid isthmus ablation: the AURUM 8 study.

  Authors: Thorsten Lewalter, Christian Weiss, Sebastian Spencker, Werner Jung, Wilhelm Haverkamp, Stephan Willems, Thomas Deneke, Josef Kautzner, Michael Wiedemann, Jürgen Siebels [......] Gerd Hindricks, Markus Zabel, Ernst Vester, Harald Schwacke, Erica Mittmann-Braun, Lars Lickfett, Sabine Hoffmeister, Jochen Proff, Christian Mewis, Wolfgang Bauer

  Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 09/2010; 13(1):102-8.

  Gold electrodes have the theoretical advantage of creating bigger lesions than platinum-iridium (Pt-Ir) electrodes. We performed a prospective randomized study to compare the clinical efficacy ofGold electrodes have the theoretical advantage of creating bigger lesions than platinum-iridium (Pt-Ir) electrodes. We performed a prospective randomized study to compare the clinical efficacy of standard 8 mm Pt-Ir tip catheter (control) and 8 mm gold-tip catheters in the ablation of the cavotricuspid isthmus (CTI)-dependent atrial flutter. A total of 463 patients undergoing CTI ablation in 19 clinical centres were randomized to receive the treatment by gold-tip or control catheter. The primary endpoint was cumulative radiofrequency (RF) application duration until achieving bidirectional CTI block. It did not differ significantly for the two catheters. The gold-tip catheter was, however, associated with a higher ablation success rate (94.3 vs. 89.0%, P = 0.042) and a substantially lower incidence of char and coagulum formation (4.8 vs. 37.9%, P < 0.001), which required exchange of 1 gold-tip (0.4%) and 10 control catheters (4.6%, P = 0.005). The gold-tip catheter delivered more mean power (52 ± 12 W) than the control catheter (48 ± 13 W, P < 0.001). Both mean and maximum temperatures measured by the thermocouple integrated in the catheter tip were statistically significantly lower in the gold (mean: 53.2 ± 4.7°C, max: 68.7 ± 6.6°C) than in the control catheter (54.3 ± 5.2 and 70.2 ± 7.0°C, respectively, P < 0.05). Fluoroscopy time, procedure duration, procedural-related complications, and arrhythmia recurrence during 6 months of follow-up did not differ between the two catheters. Owing to a higher primary ablation success rate and reduced incidence of char/coagulum formation, gold may be preferred over Pt-Ir as electrode material for 8 mm tip catheters for CTI ablation. ClinicalTrials.gov: NCT00326001 (http://clinicaltrials.gov/ct2/show/NCT00326001).

• Cardiac conduction disturbances and differential effects on atrial and ventricular electrophysiological properties in desmin deficient mice.

  Authors: Jan Wilko Schrickel, Florian Stöckigt, Wieslaw Krzyzak, Denise Paulin, Zhenlin Li, Indra Lübkemeier, Bernd Fleischmann, Philipp Sasse, Markus Linhart, Thorsten Lewalter, Georg Nickenig, Lars Lickfett, Rolf Schröder, Christoph Stephan Clemen

  Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing. 04/2010; 28(2):71-80.

  Desmin mutations in humans cause desmin-related cardiomyopathy, resulting in heart failure, atrial and ventricular arrhythmias, and sudden cardiac death. The intermediate filament desmin is stronglyDesmin mutations in humans cause desmin-related cardiomyopathy, resulting in heart failure, atrial and ventricular arrhythmias, and sudden cardiac death. The intermediate filament desmin is strongly expressed in striated muscle cells and in Purkinje fibers of the ventricular conduction system. The aim of the present study was to characterize electrophysiological cardiac properties in a desmin-deficient mouse model. The impact of desmin deficiency on cardiac electrophysiological characteristics was examined in the present study. In vivo electrophysiological studies were carried out in 29 adult desmin deficient (Des-/-) and 19 wild-type (Des+/+) mice. Additionally, epicardial activation mapping was performed in Langendorff-perfused hearts. Intracardiac electrograms showed no significant differences in AV, AH, and HV intervals. Functional testing revealed equal AV-nodal refractory periods, sinus-node recovery times, and Wenckebach points. However, compared to the wild-type situation, Des-/- mice were found to have a significantly reduced atrial (23.6+/-10.3 ms vs. 31.8+/-12.5 ms; p=0.045), but prolonged ventricular refractory period (33.0+/-8.7 ms vs. 26.7+/-6.5 ms; p=0.009). The probability of induction of atrial fibrillation was significantly higher in Des-/- mice (Des-/-: 38% vs. Des+/+: 27%; p=0.0255), while ventricular tachycardias significantly were reduced (Des-/-: 7% vs. Des+/+: 21%; p<0.0001). Epicardial activation mapping showed slowing of conduction in the ventricles of Des-/- mice. Des-/- mice exhibit reduced atrial but prolonged ventricular refractory periods and ventricular conduction slowing, accompanied by enhanced inducibility of atrial fibrillation and diminished susceptibility to ventricular arrhythmias. Desmin deficiency does not result in electrophysiological changes present in human desminopathies, suggesting that functional alterations rather than loss of desmin cause the cardiac alterations in these patients.

• Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation.

  Authors: Volker Rudolph, René P Andrié, Tanja K Rudolph, Kai Friedrichs, Anna Klinke, Birgit Hirsch-Hoffmann, Alexander P Schwoerer, Denise Lau, Xiaoming Fu, Karin Klingel [......] Wolfram-Hubertus Zimmermann, Thomas Meinertz, Rainer H Böger, Hermann Reichenspurner, Bruce A Freeman, Thomas Eschenhagen, Heimo Ehmke, Stanley L Hazen, Stephan Willems, Stephan Baldus

  Nature medicine. 03/2010; 16(4):470-4.

  Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation. However, whether inflammation is the cause or the consequence of atrialObservational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation. However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain elusive. Here we provide experimental and clinical evidence for the mechanistic involvement of myeloperoxidase (MPO), a heme enzyme abundantly expressed by neutrophils, in the pathophysiology of atrial fibrillation. MPO-deficient mice pretreated with angiotensin II (AngII) to provoke leukocyte activation showed lower atrial tissue abundance of the MPO product 3-chlorotyrosine, reduced activity of matrix metalloproteinases and blunted atrial fibrosis as compared to wild-type mice. Upon right atrial electrophysiological stimulation, MPO-deficient mice were protected from atrial fibrillation, which was reversed when MPO was restored. Humans with atrial fibrillation had higher plasma concentrations of MPO and a larger MPO burden in right atrial tissue as compared to individuals devoid of atrial fibrillation. In the atria, MPO colocalized with markedly increased formation of 3-chlorotyrosine. Our data demonstrate that MPO is a crucial prerequisite for structural remodeling of the myocardium, leading to an increased vulnerability to atrial fibrillation.

• Incidence and predictors of silent cerebral embolism during pulmonary vein catheter ablation for atrial fibrillation.

  Authors: Jan Wilko Schrickel, Lars Lickfett, Thorsten Lewalter, Erica Mittman-Braun, Stephanie Selbach, Katharina Strach, Claas P Nähle, Jörg Otto Schwab, Markus Linhart, Rene Andrié, Georg Nickenig, Torsten Sommer

  Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 11/2009;

  Aims Left atrial catheter ablation of the pulmonary veins (PV) has evolved as an important therapeutic option for the treatment of atrial fibrillation (AF). We aimed to investigate the incidence andAims Left atrial catheter ablation of the pulmonary veins (PV) has evolved as an important therapeutic option for the treatment of atrial fibrillation (AF). We aimed to investigate the incidence and predictors of silent cerebral embolism associated with PV catheter ablation, detected by diffusion-weighted magnetic resonance imaging (DW-MRI). Methods and results We performed a prospective analysis of 53 consecutive patients with persistent or paroxysmal AF that underwent PV ablation and post-procedural cerebral MRI 1 day after lasso catheter-guided ostial PV ablation. Patients were analysed for possible demographical, medical, echocardiographical, and procedural predictors of embolic events. A mean of 3.5 +/- 0.5 PVs were ablated per patient. In six patients, DW-MRI depicted new clinically silent microembolism after PV ablation (11%). The number of ineffective medical antiarrhythmic agents prior to ablation procedure was significantly higher in the embolism group (3.3 +/- 0.5 vs. 2.2 +/- 1.4, P = 0.014). Coronary heart disease (CAD) was more frequent in patients with cerebral embolisms (33 vs. 2%, P = 0.031); left ventricular volume (130 +/- 12 vs. 103 +/- 26 mL, P = 0.002), and septal wall thickness (13.0 +/- 1.4 vs. 7.9 +/- 4.8 mm, P = 0.025) were significantly increased. Conclusion This study shows a high incidence of silent micro-embolic events after PV ablation. CAD, left ventricular dilatation, and hypertrophy were potential predictors of this complication.

• Comparison of Cryoballoon and Radiofrequency Ablation of Pulmonary Veins in 40 Patients with Paroxysmal Atrial Fibrillation: A Case-Control Study.

  Authors: Markus Linhart, Barbara Bellmann, Erica Mittmann-Braun, Jan W Schrickel, Alexander Bitzen, René Andrié, Alexander Yang, Georg Nickenig, Lars Lickfett, Thorsten Lewalter

  Journal of cardiovascular electrophysiology. 08/2009;

  Comparison of Cryoballoon and RF Ablation of PV. Introduction: Ablation of pulmonary veins (PV) is an established therapeutic option for patients with symptomatic drug-refractory paroxysmal atrialComparison of Cryoballoon and RF Ablation of PV. Introduction: Ablation of pulmonary veins (PV) is an established therapeutic option for patients with symptomatic drug-refractory paroxysmal atrial fibrillation (AF). Radiofrequency (RF) is currently the most widespread energy source for PV ablation. Cryothermal energy applied with a cryoballoon technique as an alternative has recently evolved. Methods and Results: In a case-control setting, we compared 20 patients with paroxysmal AF who underwent their first PV ablation with the cryoballoon technique to 20 matched patients with conventional RF ablation. In the case of persistent electrical potentials after cryoballoon ablation, it was combined with ablation with a conventional cryocatheter. All patients performed daily event recording for 3 months after ablation procedure. Ablation parameters and success rate after 3 and 6 months were compared. In the cryoballoon group, the overall success rate was 55% (50% in the cryoballoon only group [14 patients] and 66% in the combination group [6 patients]), as opposed to the RF group with 45%. AF episode burden was lower after cryoballoon ablation. There was no significant difference between cryoballoon and RF ablation regarding procedure parameters. In the cryoballoon group, 3 phrenic nerve palsies occurred using the 23 mm balloon that resolved spontaneously. Conclusion: PV ablation with the cryoballoon technique is feasible and seems to have a similar success rate in comparison to RF ablation. Procedure- and fluoroscopy duration are not longer than in conventional RF ablation.

• Lack of gelsolin promotes perpetuation of atrial fibrillation in the mouse heart.

  Authors: Jan Schrickel, Klaus Fink, Rainer Meyer, Christian Grohé, Florian Stoeckigt, Klaus Tiemann, Alexander Ghanem, Lars Lickfett, Georg Nickenig, Thorsten Lewalter

  Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing. 08/2009;

  PURPOSE: Gelsolin (gsn) is involved in the reorganization of the cytoskeleton, thereby modulating cardiomyocytal L-type Ca(2+) channels. We investigated global cardiac electrophysiologicalPURPOSE: Gelsolin (gsn) is involved in the reorganization of the cytoskeleton, thereby modulating cardiomyocytal L-type Ca(2+) channels. We investigated global cardiac electrophysiological characteristics in a gsn-deficient (gsn(-/-)) mouse strain. METHODS: Using transvenous catheterization, atrial and ventricular stimulation were performed in 15 male mice [eight gsn(-/-), seven wild-type (gsn(+/+))]. Surface ECG, standard electrophysiological parameters, and inducibility of atrial fibrillation (AF) were evaluated. RESULTS: The surface ECG showed shorter PQ (37.8 +/- 4.6 versus 42.9 +/- 2.7 ms; P = 0.02), but longer QRS (16.5 +/- 1.8 versus 13.9 +/- 1.2 ms; P = 0.005) and QT intervals (38.5 +/- 2.2 versus 35.6 +/- 2.4 ms, P = 0.03) in gsn(-/-). Gsn(-/-) exhibited significantly higher susceptibility to induction of prolonged AF episodes >/=60 s [six of eight gsn(-/-) versus one of seven gsn(+/+); P = 0.04]. Sustained AF episodes >/=10 min were observed in 50% of the gsn-deficient animals. CONCLUSIONS: Gsn deficiency results in perpetuation of inducible episodes of atrial fibrillation. Altered L-type Ca(2+) currents and disturbed Ca(2+) handling known to be associated to gsn deficiency likely contribute to this effect.

• Normal impulse propagation in the atrioventricular conduction system of Cx30.2/Cx40 double deficient mice.

  Authors: Jan W Schrickel, Maria M Kreuzberg, Alexander Ghanem, Jung-Sun Kim, Markus Linhart, Rene Andrié, Klaus Tiemann, Georg Nickenig, Thorsten Lewalter, Klaus Willecke

  Journal of molecular and cellular cardiology. 03/2009;

  Connexin (Cx) 30.2, Cx40 and Cx45 containing gap junctional channels contribute to electrical impulse propagation through the mouse atrioventricular node (AV-node). The cross talk in between theseConnexin (Cx) 30.2, Cx40 and Cx45 containing gap junctional channels contribute to electrical impulse propagation through the mouse atrioventricular node (AV-node). The cross talk in between these Cxs may be of great importance for AV-nodal conduction. We generated Cx30.2/Cx40 double deficient mice (Cx30.2(LacZ/LacZ)Cx40(-/-)) and analyzed the relative impact of Cx30.2 and Cx40 on cardiac conductive properties in vivo by use of electrophysiological examination. Cx30.2(LacZ/LacZ)Cx40(-/-) mice exhibited neither obvious cardiac malformations nor impaired contractile function. In surface ECG analyses, Cx30.2(LacZ/LacZ)Cx40(-/-) and Cx40 deficient animals (Cx40(-/-)) showed significantly longer P-wave durations, PQ-intervals and prolonged QRS complexes relative to wild-type littermates (WT). Cx30.2-deficient mice (Cx30.2(LacZ/LacZ)) developed shorter PQ-intervals as compared to WT, Cx40(-/-) or Cx30.2/Cx40 double deficient mice. Intracardiac evaluation of the atria-His (AH) and His-ventricle (HV) intervals representing supra and infra-Hisian conduction yielded significant acceleration of supra-Hisian conductivity in Cx30.2(LacZ/LacZ) (AH: 28.2+/-4.3 ms) and prolongation of infra-Hisian conduction in Cx40(-/-) mice (HV: 13.7+/-2.6 ms). These parameters were unchanged in the Cx30.2(LacZ/LacZ)Cx40(-/-) mice (AH: 37.3+/-5.5 ms, HV: 11.7+/-2.6 ms), which exhibited AV-nodal and ventricular conduction times similar to WT animals (AH: 35.9+/-4.4 ms, HV: 10.5+/-1.9 ms). We conclude that the remaining Cx45 gap junctional channels are sufficient to maintain electrical coupling and cardiac impulse propagation in the AV-node and proximal ventricular conduction system in mice. We suggest that Cx30.2 and Cx40 act as counterparts in the AV-node and His-bundle, decreasing or increasing, respectively, electrical coupling and conduction velocity in these areas.

• In vitro comparison of platinum-iridium and gold tip electrodes: lesion depth in 4 mm, 8 mm, and irrigated-tip radiofrequency ablation catheters.

  Authors: Markus Linhart, Hanke Mollnau, Alexander Bitzen, Sabine Wurtz, Jan W Schrickel, René Andrié, Florian Stöckigt, Christian Weiß, Georg Nickenig, Lars M Lickfett, Thorsten Lewalter

  Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 02/2009;

  Aims We compared a newly developed irrigated gold tip electrode ablation catheter and a gold tip 4 and 8 mm catheter with the corresponding platinum-iridium (Pt) tip catheters in an in vitro setting.Aims We compared a newly developed irrigated gold tip electrode ablation catheter and a gold tip 4 and 8 mm catheter with the corresponding platinum-iridium (Pt) tip catheters in an in vitro setting. Methods and results In a flow chamber simulating physiological flow conditions, radiofrequency catheter ablation was performed on tissue samples of porcine endomyocardium and liver. Lesion depth, energy and temperature delivery, and popping frequency were determined. Two hundred and fifty-three ablations were conducted. Four and eight millimetre, gold tip electrode catheters produced significantly deeper lesions compared with the Pt tip electrode (liver 4 mm: 4.67 +/- 1.7 vs. 2.9 +/- 1.0 mm, P < 0.0001; endomyocardium 4 mm: 3.88 +/- 1.1 vs. 2.81 +/- 0.7 mm, P < 0.001; liver 8 mm: 3.98 +/- 1.0 vs. 2.03 +/- 1.1 mm, P < 0.001; endomyocardium 8 mm: 4.00 +/- 0.9 vs. 3.39 +/- 0.8 mm, P < 0.001) and correlated with the amount of energy delivery. Popping frequency was significantly higher in gold tip electrodes. In irrigated tip electrodes, there was no difference in the lesion depth comparing gold with Pt (liver: 5.18 +/- 0.7 vs. 5.01 +/- 0.7 mm, P = ns; endomyocardium: 4.89 +/- 0.7 vs. 4.78 +/- 0.8 mm, P = ns). There was a trend towards less popping in the gold tip electrode. Conclusion Both 4 and 8 mm not-irrigated gold tip catheters produced deeper lesions than the corresponding Pt tip catheter. In irrigated tip catheters, gold and Pt tip material did not show differences in the lesion depth.

• Interventional Electrophysiology: New frontiers for an ever expanding discipline.

  Authors: Thorsten Lewalter, Sanjeev Saksena

  Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing. 09/2008; 22(2):85-6.

• Advanced mapping techniques in atrial fibrillation.

  Authors: Lars Lickfett, Jörg O Schwab, Thorsten Lewalter

  Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing. 09/2008; 22(2):155-9.

  Catheter ablation has emerged as an excellent treatment option for atrial fibrillation especially in patients with paroxysmal AF. Several obstacles however remain regarding ablation strategies forCatheter ablation has emerged as an excellent treatment option for atrial fibrillation especially in patients with paroxysmal AF. Several obstacles however remain regarding ablation strategies for persistent and chronic AF. In this setting, adequate success rates can only be achieved with left atrial ablation in addition to complete PV isolation. Important techniques in this regard are mapping of complex fractionated atrial electrograms as well as identification of atrial sites serving as sources of persistent AF. Other mapping techniques reviewed in this article are rapid geometry acquisition with spiral catheters and the Ensite/NAVX system, the 64-pole Constellation basket catheter as well as the MESH Mapper catheter.

• The conditional connexin43G138R mouse mutant represents a new model of hereditary oculodentodigital dysplasia in humans.

  Authors: Radoslaw Dobrowolski, Philipp Sasse, Jan W Schrickel, Marcus Watkins, Jung-Sun Kim, Mindaugas Rackauskas, Clemens Troatz, Alexander Ghanem, Klaus Tiemann, Joachim Degen, Feliksas F Bukauskas, Roberto Civitelli, Thorsten Lewalter, Bernd K Fleischmann, Klaus Willecke

  Human molecular genetics. 03/2008; 17(4):539-54.

  Oculodentodigital dysplasia (ODDD) is a dominant negatively inherited disorder with variable but characteristic anomalies of the fingers and toes, eyes, face and teeth, which are caused by mutationsOculodentodigital dysplasia (ODDD) is a dominant negatively inherited disorder with variable but characteristic anomalies of the fingers and toes, eyes, face and teeth, which are caused by mutations in the connexin 43 (Cx43) gene. All mutations analyzed so far have a negative influence on the conductance through gap junctional channels and hemichannels, as well as trafficking of Cx43 protein in transfected cells. In this study, we inserted the human Cx43G138R point mutation into the mouse Cx43 gene and generated mice conditionally expressing this mutation. All ODDD phenotypic manifestations observed in humans, including syndactyly and enamel hypoplasia as well as craniofacial, bone and heart anomalies, were also observed with significant penetrance in Cx43G138R mice. When this mutation was specifically expressed in cardiomyocytes, characteristic alterations in the electrocardiogram and spontaneous arrhythmias were recorded. In vitro studies with Cx43G138R-expressing cells revealed loss of the Cx43 P2 phosphorylation state, which was also absent in the mutated hearts. This loss has previously been associated with gap junctional dysfunction and increased cellular ATP release. The Cx43G138R mutated mice show significantly increased arrhythmogeneity ex vivo in Langendorff experiments with explanted hearts and in vivo in particular under hypoxic conditions. Our results suggest that the increased activity of ATP-releasing channels in Cx43G138R mutated cardiomyocytes may further reduce the already decreased gap junctional communication and thus aggravate arrhythmogenesis in the mouse mutant.

• Recovery from ultra-high dose organophosphate poisoning after "in-the-field" antidote treatment: Potential lessons for civil defense.

  Authors: Jan Wilko Schrickel, Thorsten Lewalter, Berndt Lüderitz, Georg Nickenig, Hans-Ulrich Klehr, Christian Rabe

  The Journal of emergency medicine. 03/2008;

  Organophosphate poisoning is associated with a high mortality rate due to respiratory failure, dysrhythmias, and multi-organ failure. We report two cases of survival after "in-the field" antidoteOrganophosphate poisoning is associated with a high mortality rate due to respiratory failure, dysrhythmias, and multi-organ failure. We report two cases of survival after "in-the field" antidote treatment of very severe organophosphate poisonings. Two patients orally ingested large amounts of the organophosphorous agent oxydemeton-methyl in suicide attempts, resulting in the hypercholinergic syndrome in both. Resuscitation included early administration of antidote by emergency medical personnel as well as high-dose atropine. Plasma levels of pseudo cholinesterase were initially very low in both patients. Long-term mechanical ventilation was necessary, and both patients developed aspiration pneumonia. At discharge, no major neurological deficits were present. Prompt antidote treatment and aggressive supportive emergency and intensive care unit therapy contribute to improved survival after acute organophosphate poisoning. We believe that in cases of mass poisonings-for example, terrorist activity-therapy must be available on the scene as soon as possible. This also may require decentralized antidote storage.

• Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia.

  Authors: Wilhelm Roell, Thorsten Lewalter, Philipp Sasse, Yvonne N Tallini, Bum-Rak Choi, Martin Breitbach, Robert Doran, Ulrich M Becher, Seong-min Hwang, Toktam Bostani [......] Shaun Reining, Britta Eiberger, Bethann Gabris, Alexander Pfeifer, Armin Welz, Klaus Willecke, Guy Salama, Jan W Schrickel, Michael I Kotlikoff, Bernd K Fleischmann

  Nature. 01/2008; 450(7171):819-24.

  Ventricular tachyarrhythmias are the main cause of sudden death in patients after myocardial infarction. Here we show that transplantation of embryonic cardiomyocytes (eCMs) in myocardial infarctsVentricular tachyarrhythmias are the main cause of sudden death in patients after myocardial infarction. Here we show that transplantation of embryonic cardiomyocytes (eCMs) in myocardial infarcts protects against the induction of ventricular tachycardia (VT) in mice. Engraftment of eCMs, but not skeletal myoblasts (SMs), bone marrow cells or cardiac myofibroblasts, markedly decreased the incidence of VT induced by in vivo pacing. eCM engraftment results in improved electrical coupling between the surrounding myocardium and the infarct region, and Ca2+ signals from engrafted eCMs expressing a genetically encoded Ca2+ indicator could be entrained during sinoatrial cardiac activation in vivo. eCM grafts also increased conduction velocity and decreased the incidence of conduction block within the infarct. VT protection is critically dependent on expression of the gap-junction protein connexin 43 (Cx43; also known as Gja1): SMs genetically engineered to express Cx43 conferred a similar protection to that of eCMs against induced VT. Thus, engraftment of Cx43-expressing myocytes has the potential to reduce life-threatening post-infarct arrhythmias through the augmentation of intercellular coupling, suggesting autologous strategies for cardiac cell-based therapy.

• Morphology-enhanced atrial event classification improves sensing in pacemakers.

  Authors: Thorsten Lewalter, Ype Tuininga, Gerd Fröhlig, Susann Remerie, Frank Eberhardt, Jörg Schmidt, Chris Van Groeningen, Peter Wohlgemuth

  Pacing and clinical electrophysiology : PACE. 12/2007; 30(12):1455-63.

  BACKGROUND: In atrial-based pacing, appropriate therapy and reliable diagnostics depend on detection and discrimination of atrial signals. Accurate classification of atrial events is mainlyBACKGROUND: In atrial-based pacing, appropriate therapy and reliable diagnostics depend on detection and discrimination of atrial signals. Accurate classification of atrial events is mainly confounded by oversensing of ventricular far-field R-wave signals (FFRW), but attempts to reject FFRWs by manipulating atrial sensitivity and/or postventricular atrial blanking period (PVAB) may result in undersensing (especially of atrial fibrillation, AF) or in 2:1 atrial flutter detection. The objective of this study is therefore to evaluate if such methods can be improved by morphology-enhanced atrial event classification (MORPH). METHODS: Twenty-four-hour ambulatory atrial electrograms were recorded from continuous telemetry of digital pacemakers. Half of the recording was used for collecting two individual morphology parameters that discriminated P-waves from FFRWs in every patient (learning phase). The other half was used to test the MORPH algorithm against traditional methods (classification phase). RESULTS: In 44/48 patients, data were suitable for analysis. Average P and FFRW amplitudes were 1.96 mV versus 0.61 mV (P < 0.001). The interval between ventricular events and FFRW oversensing (VA interval) averaged at 14 ms during sensing and at 118 ms during pacing in the ventricle. Compared to nominal ("Factory") settings, the MORPH algorithm improved the sensitivity for P-wave recognition from 97.2% to 99.2%, the specificity from 91.9% to 99.96%, and the accuracy from 95.3% to 99.4% (P < 0.01 for all). CONCLUSIONS: By improving atrial signal discrimination, morphology analysis of atrial electrograms allows for high atrial sensitivity settings, and potentially improves the reliability of atrial arrhythmia diagnostics in heart rhythm devices.

• Enhanced heterogeneity of myocardial conduction and severe cardiac electrical instability in annexin A7-deficient mice.

  Authors: Jan W Schrickel, Klara Brixius, Claudia Herr, Christoph S Clemen, Philipp Sasse, Kathrin Reetz, Christian Grohé, Rainer Meyer, Klaus Tiemann, Rolf Schröder, Wilhelm Bloch, Georg Nickenig, Bernd K Fleischmann, Angelika A Noegel, Robert H G Schwinger, Thorsten Lewalter

  Cardiovascular research. 11/2007; 76(2):257-68.

  OBJECTIVES: Annexin A7 is involved in cardiomyocyte membrane organization and Ca(2+)-dependent signalling processes. We investigated the impact of annexin A7 on cardiac electrophysiologicalOBJECTIVES: Annexin A7 is involved in cardiomyocyte membrane organization and Ca(2+)-dependent signalling processes. We investigated the impact of annexin A7 on cardiac electrophysiological properties using an annexin A7-deficient mouse strain (annexin A7(-/-)). METHODS: Nineteen adult annexin A7(-/-) and 14 wild-type mice were examined electrophysiologically in vivo by transvenous catheterization. Hearts were additionally perfused by the Langendorff method and epicardial activation mapping was performed. RESULTS: The susceptibility to induction of atrial fibrillation was elevated in annexin A7(-/-) mice. Ten deficient animals showed atrial fibrillation (AF) episodes > or =1 min and sustained AF > or =30 min was observed in 4 annexin A7(-/-) mice, but in none of the wild-type mice. The incidence of ventricular tachycardia (VT) was higher in annexin A7(-/-) mice and VT duration was prolonged. Epicardial mapping showed elevated anisotropy and inhomogeneity of conduction, leading to conduction blocks in the deficient mice. Besides alterations of intracellular calcium homeostasis, electron microscopy showed a homogeneous, electron-dense material that filled the myocardial intercellular compartments and accumulated at the basement membranes. This led to expansion of the extracellular spaces, which was the most probable substrate factor responsible for the disturbances of electrical communication. CONCLUSIONS: Annexin A7 deficiency causes severe electrical instability in the murine heart, including conduction disturbances and anisotropy of impulse propagation, which is accompanied by disturbed calcium handling and intercellular deposits.

• Automatic p wave analysis over 24 hours in patients with paroxysmal or persistent atrial fibrillation.

  Authors: Alexander Bitzen, Karsten Sternickel, Thorsten Lewalter, Jörg Otto Schwab, Alexander Yang, Jan Wilko Schrickel, Markus Linhart, Christian Wolpert, Werner Jung, Peter David, Berndt Lüderitz, Georg Nickenig, Lars Lickfett

  Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 10/2007; 12(4):306-15.

  BACKGROUND: Patients with atrial fibrillation (AF) often exhibit abnormalities of P wave morphology during sinus rhythm. We examined a novel method for automatic P wave analysis in theBACKGROUND: Patients with atrial fibrillation (AF) often exhibit abnormalities of P wave morphology during sinus rhythm. We examined a novel method for automatic P wave analysis in the 24-hour-Holter-ECG of 60 patients with paroxysmal or persistent AF and 12 healthy subjects. METHODS: Recorded ECG signals were transferred to the analysis program where 5-10 P and R waves were manually marked. A wavelet transform performed a time-frequency decomposition to train neural networks. Afterwards, the detected P waves were described using a Gauss function optimized to fit the individual morphology and providing amplitude and duration at half P wave height. RESULTS: >96% of P waves were detected, 47.4 +/- 20.7% successfully analyzed afterwards. In the patient population, the mean amplitude was 0.073 +/- 0.028 mV (mean variance 0.020 +/- 0.008 mV(2)), the mean duration at half height 23.5 +/- 2.7 ms (mean variance 4.2 +/- 1.6 ms(2)). In the control group, the mean amplitude (0.105 +/- 0.020 ms) was significantly higher (P < 0.0005), the mean variance of duration at half height (2.9 +/- 0.6 ms(2)) significantly lower (P < 0.0085). CONCLUSIONS: This method shows promise for identification of triggering factors of AF.