Martin Borggrefe

Publications of Martin Borggrefe

• The G534E-polymorphism of the gene encoding the Factor VII-activating protease is a risk factor for venous thrombosis and recurrent events.

  Authors: Parviz Ahmad-Nejad, Carl-Erik Dempfle, Christel Weiss, Peter Bugert, Martin Borggrefe, Michael Neumaier

  Thrombosis research. 03/2012;

  INTRODUCTION: A single nucleotide polymorphism of the factor VII activating protease (FSAP), FSAP Marburg I (rs7080536) has been identified as a risk factor for venous thrombosis, but its clinicalINTRODUCTION: A single nucleotide polymorphism of the factor VII activating protease (FSAP), FSAP Marburg I (rs7080536) has been identified as a risk factor for venous thrombosis, but its clinical role has so far been controversial in part due to small cohort sizes. The aim of the present case-control study was to elucidate the impact of the FSAP Marburg I polymorphism (FSAP-MI) on the development of venous thromboembolic disease (VTE) with other known sequence variations, including Factor V Leiden (rs6025) and Factor II G20210A (rs1799963). MATERIALS AND METHODS: The study included 891 patients (312 male and 579 female) with a history of deep venous thrombosis (DVT) and/or pulmonary embolism (PE) and 1283 healthy blood donors with no history of venous thromboembolic disease. RESULTS: We found that besides to the well-established aforementioned sequence variations of FV and Prothrombin, the FSAP Marburg I (FSAP-MI) polymorphism was significantly associated with the development of DVTs (1.65 (1.16-2.34) OR (95% CI)) and recurrent thromboembolic events (DVT and PE) (2.13 (1.35-3.36) OR (95% CI)). Comparing patients displaying one or more events FSAP-MI was still associated with the development of recurrent thromboembolic events (1.64 (1- 2.69) OR (95% CI)). CONCLUSIONS: We conclude that FSAP Marburg-I genotyping may be used to determine the risk for thromboembolic disorders in patients with suspected thrombophilia and known DVT or PE.

• Tackling myocardial metabolism: One year evaluation of free fatty acids, norephinephrine and NT-proBNP in ventricular fibrillation during STEMI.

  Authors: Michael Behnes, Thorsten Kälsch, Siegfried Lang, Tim Süselbeck, Martin Borggrefe, Elif Elmas

  International journal of cardiology. 01/2012; 155(2):291-3.

• Cellular imaging of human atherosclerotic lesions by intravascular electric impedance spectroscopy.

  Authors: Ines Streitner, Markus Goldhofer, Sungbo Cho, Ralf Kinscherf, Hagen Thielecke, Martin Borggrefe, Tim Süselbeck, Florian Streitner

  PloS one. 01/2012; 7(4):e35405.

  Newer techniques are required to identify atherosclerotic lesions that are prone to rupture. Electric impedance spectroscopy (EIS) is able to provide information about the cellular composition ofNewer techniques are required to identify atherosclerotic lesions that are prone to rupture. Electric impedance spectroscopy (EIS) is able to provide information about the cellular composition of biological tissue. The present study was performed to determine the influence of inflammatory processes in type Va (lipid core, thick fibrous cap) and Vc (abundant fibrous connective tissue while lipid is minimal or even absent) human atherosclerotic lesions on the electrical impedance of these lesions measured by EIS. EIS was performed on 1 aortic and 3 femoral human arteries at 25 spots with visually heavy plaque burden. Severely calcified lesions were excluded from analysis. A highly flexible micro-electrode mounted onto a balloon catheter was placed on marked regions to measure impedance values at 100 kHz. After paraffin embedding, visible marked cross sections (n = 21) were processed. Assessment of lesion types was performed by Movats staining. Immunostaining for CD31 (marker of neovascularisation), CD36 (scavenger cells) and MMP-3 (matrix metalloproteinase-3) was performed. The amount of positive cells was assessed semi-quantitatively. 15 type Va lesions and 6 type Vc lesions were identified. Lesions containing abundant CD36-, CD31- and MMP-3-positive staining revealed significantly higher impedance values compared to lesions with marginal or without positive staining (CD36+455±50 Ω vs. CD36- 346±53 Ω, p = 0.001; CD31+436±43 Ω vs. CD31- 340±55 Ω, p = 0.001; MMP-3+ 400±68 Ω vs. MMP-3- 323±33 Ω, p = 0.03). Atherosclerotic lesions with abundant neovascularisation (CD31), many scavenger receptor class B expressing cells (CD36) or high amount of MMP-3 immunoreactivity reveal significantly higher impedance values compared to lesions with marginal or no detection of immunoreactivity. Findings suggest that inflammatory processes in vulnerable plaques affect the impedance of atherosclerotic lesions and might therefore be detected by EIS.

• Predictors of long-term success after catheter ablation of atriofascicular accessory pathways.

  Authors: Gerold Mönnig, Kristina Wasmer, Peter Milberg, Peter Schulz, Julia Köbe, Stephan Zellerhoff, Simon Kochhäuser, Christian Pott, Gerhard Hindricks, Martin Borggrefe, Günter Breithardt, Lars Eckardt

  Heart rhythm : the official journal of the Heart Rhythm Society. 12/2011;

  BACKGROUND: Electrophysiologic characteristics, mapping strategies, and acute success rates of radiofrequency catheter ablation of atriofascicular accessory pathways are well described. However, dataBACKGROUND: Electrophysiologic characteristics, mapping strategies, and acute success rates of radiofrequency catheter ablation of atriofascicular accessory pathways are well described. However, data on long-term prognosis and predictors for freedom from arrhythmias are lacking. OBJECTIVE: To report our 20-year single-center experience on ablation of atriofascicular fibers. METHOD: Between 1992 and 2010, 34 patients with atriofascicular accessory pathways underwent catheter ablation at our institution because of symptomatic antidromic atrioventricular reentrant tachycardias. Radiofrequency procedures were retrospectively analyzed, and patients were followed for recurrences of tachyarrhythmias. Electrocardiograms (before and after ablation and at follow-up) were analyzed for each patient. RESULTS: Successful catheter ablation of the atriofascicular fiber was achieved in 23 (68%) patients. Mechanical block during mapping occurred in 3 (9%) patients, and in 2 of them ablation was performed at the site of mechanical block. Mere modification of conduction properties of the pathway without complete block was achieved in 5 patients (15%). Fast pathway ablation was performed in 2 (6%) of the patients ablated in the early 1990s. During follow-up of 9.3 ± 5.5 years, 24 patients (71%) remained free of tachyarrhythmias, 7 reported significant improvement, and 3 (9%) had no change in symptoms after ablation. Long-term success was identical between patients from the first (1992-1999) and second (2000-2010) decade (12 of 17 [71%] vs 12 of 17 [71%]). It was 87% in those with complete block of the atriofascicular fiber while all patients with mechanical block during mapping reported recurrences. Fast pathway ablation was complicated by complete atrioventricular block in 1 patient, who required pacemaker implantation 18 years after ablation owing to loss of conduction properties of the atriofascicular fiber over the years. On analyzing patients with preexcitation before ablation (n = 16; 47%), we found that the PR interval after ablation was significantly longer only in those without recurrence (162 ± 21 ms vs 134 ± 21 ms; P = .042). None of the other analyzed electrocardiographic parameters, including PR, QRS duration, and preexcitation, had prognostic impact. CONCLUSION: Acute success of complete ablation of atriofascicular pathways is associated with excellent long-term success (87%). Mere modification of conduction properties of atriofascicular fibers or ablation at the sites of mechanical block are less promising end points of ablation with high recurrence rates. Technical innovations during decades may not further improve long-term outcome in these patients.

• A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na(v)1.5 and K(v)4.3 channel currents.

  Authors: Dan Hu, Hector Barajas-Martínez, Argelia Medeiros-Domingo, Lia Crotti, Christian Veltmann, Rainer Schimpf, Janire Urrutia, Aintzane Alday, Oscar Casis, Ryan Pfeiffer, Elena Burashnikov, Gabriel Caceres, David J Tester, Christian Wolpert, Martin Borggrefe, Peter Schwartz, Michael J Ackerman, Charles Antzelevitch

  Heart rhythm : the official journal of the Heart Rhythm Society. 12/2011;

  BACKGROUND: Cardiac sodium channel β-subunit mutations have been associated with several inherited cardiac arrhythmia syndromes. OBJECTIVE: To identify and characterize variations in SCN1BbBACKGROUND: Cardiac sodium channel β-subunit mutations have been associated with several inherited cardiac arrhythmia syndromes. OBJECTIVE: To identify and characterize variations in SCN1Bb associated with Brugada syndrome (BrS) and sudden infant death syndrome (SIDS). METHODS: All known exons and intron borders of the BrS-susceptibility genes were amplified and sequenced in both directions. Wild type (WT) and mutant genes were expressed in TSA201 cells and studied using co-immunoprecipitation and whole-cell patch-clamp techniques. RESULTS: Patient 1 was a 44-year-old man with an ajmaline-induced type 1 ST-segment elevation in V1 and V2 supporting the diagnosis of BrS. Patient 2 was a 62-year-old woman displaying a coved-type BrS electrocardiogram who developed cardiac arrest during fever. Patient 3 was a 4-month-old female SIDS case. A R214Q variant was detected in exon 3A of SCN1Bb (Na(v)1B) in all three probands, but not in any other gene previously associated with BrS or SIDS. R214Q was identified in 4 of 807 ethnically-matched healthy controls (0.50%). Co-expression of SCN5A/WT + SCN1Bb/R214Q resulted in peak sodium channel current (I(Na)) 56.5% smaller compared to SCN5A/WT + SCN1Bb/WT (n = 11-12, P<0.05). Co-expression of KCND3/WT + SCN1Bb/R214Q induced a Kv4.3 current (transient outward potassium current, I(to)) 70.6% greater compared with KCND3/WT + SCN1Bb/WT (n = 10-11, P<0.01). Co-immunoprecipitation indicated structural association between Na(v)β1B and Na(v)1.5 and K(v)4.3. CONCLUSION: Our results suggest that R214Q variation in SCN1Bb is a functional polymorphism that may serve as a modifier of the substrate responsible for BrS or SIDS phenotypes via a combined loss of function of sodium channel current and gain of function of transient outward potassium current.

• A mobile structure at the entrance of the left atrial appendage in a patient with malignant fibrous histiocytoma.

  Authors: Elif Elmas, Thorsten Kälsch, Martin Borggrefe, Dariush Haghi

  Anadolu kardiyoloji dergisi : AKD = the Anatolian journal of cardiology. 12/2011; 11(8):741-2.

• Molecular genetic and functional association of Brugada and early repolarization syndromes with S422L missense mutation in KCNJ8.

  Authors: Hector Barajas-Martínez, Dan Hu, Tania Ferrer, Carlos G Onetti, Yuesheng Wu, Elena Burashnikov, Madalene Boyle, Tyler Surman, Janire Urrutia, Christian Veltmann, Rainer Schimpf, Martin Borggrefe, Christian Wolpert, Bassiema B Ibrahim, José Antonio Sánchez-Chapula, Stephen Winters, Michel Haïssaguerre, Charles Antzelevitch

  Heart rhythm : the official journal of the Heart Rhythm Society. 11/2011;

  BACKGROUND: Adenosine triphosphate (ATP)-sensitive potassium cardiac channels consist of inward-rectifying channel subunits Kir6.1 or Kir6.2 (encoded by KCNJ8 or KCNJ11) and the sulfonylurea receptorBACKGROUND: Adenosine triphosphate (ATP)-sensitive potassium cardiac channels consist of inward-rectifying channel subunits Kir6.1 or Kir6.2 (encoded by KCNJ8 or KCNJ11) and the sulfonylurea receptor subunits SUR2A (encoded by ABCC9). OBJECTIVE: To examine the association of mutations in KCNJ8 with Brugada syndrome (BrS) and early repolarization syndrome (ERS) and to elucidate the mechanism underlying the gain of function of ATP-sensitive potassium channel current. METHODS: Direct sequencing of KCNJ8 and other candidate genes was performed on 204 BrS and ERS probands and family members. Whole-cell and inside-out patch-clamp methods were used to study mutated channels expressed in TSA201 cells. RESULTS: The same missense mutation, p.Ser422Leu (c.1265C>T) in KCNJ8, was identified in 3 BrS and 1 ERS probands but was absent in 430 alleles from ethnically matched healthy controls. Additional genetic variants included CACNB2b-D601E. Whole-cell patch-clamp studies showed a 2-fold gain of function of glibenclamide-sensitive ATP-sensitive potassium channel current when KCNJ8-S422L was coexpressed with SUR2A-wild type. Inside-out patch-clamp evaluation yielded a significantly greater half maximal inhibitory concentration for ATP in the mutant channels (785.5 ± 2 vs 38.4 ± 3 μM; n = 5; P <.01), pointing to incomplete closing of the ATP-sensitive potassium channels under normoxic conditions. Patients with a CACNB2b-D601E polymorphism displayed longer QT/corrected QT intervals, likely owing to their effect to induce an increase in L-type calcium channel current (I(Ca-L)). CONCLUSIONS: Our results support the hypothesis that KCNJ8 is a susceptibility gene for BrS and ERS and point to S422L as a possible hotspot mutation. Our findings suggest that the S422L-induced gain of function in ATP-sensitive potassium channel current is due to reduced sensitivity to intracellular ATP.

• Comparison of ventricular tachyarrhythmia characteristics in patients with idiopathic dilated or ischemic cardiomyopathy and defibrillators implanted for primary prevention.

  Authors: Florian Streitner, Juergen Kuschyk, Claudia Dietrich, Eva Mahl, Ines Streitner, Christina Doesch, Christian Veltmann, Rainer Schimpf, Christian Wolpert, Martin Borggrefe

  Clinical cardiology. 09/2011; 34(10):604-9.

  Implantable cardioverter-defibrillator (ICD) therapy for primary prevention is well established in ischemic cardiomyopathy (ICM). Data on the role of ICDs in patients with dilated cardiomyopathyImplantable cardioverter-defibrillator (ICD) therapy for primary prevention is well established in ischemic cardiomyopathy (ICM). Data on the role of ICDs in patients with dilated cardiomyopathy (DCM) and no history of ventricular tachyarrhythmia (VT/VF) are more limited. DCM patients with an impaired left ventricular ejection fraction (LVEF) still represent a low arrhythmic risk subgroup in clinical practice. ICD stored data of DCM patients with an LVEF ≤35% was compared to data of ICM patients meeting Multicenter Automatic Defibrillator Implantation Trial (MADIT) eligibility criteria. VT/VF occurrences and electrical storm (ES) events were analyzed. There were 652 patients followed for 50.9 ± 33.9 months. There were 1978 VT and 241 VF episodes analyzed in 66 out of 203 patients (32.5%) with DCM and in 118 out of 449 patients (26.3%, P = 0.209) with ICM. Freedom of appropriate ICD treatment due to VT/VF or ES events did not differ in both patient populations (log-rank, P>0.05). In patients presenting with VT/VF episodes, mean event rates were comparable in both patient populations (3.2 ± 14.1 for DCM and VT vs 3 ± 13.9 for ICM and VT [P = 0.855], 0.4 ± 1.3 for DCM and VF vs 0.4 ± 1.8 for ICM and VF [P = 0.763], and 0.2 ± 0.7 for DCM and ES vs 0.2 ± 1 for ICM and ES [P = 0.666]). DCM patients with prophylactic ICDs implanted due to heart failure and patients fulfilling MADIT criteria reveal comparable patterns of VT/VF/ES events during long-term follow-up. Incidence, mean number of events, and time to first event did not differ significantly. Findings support the current guidelines for prophylactic ICD therapy in DCM patients with heart failure.

• From ECG to mutation: programmed ventricular stimulation providing a link to genetics of cardiac channelopathies.

  Authors: Rainer Schimpf, Martin Borggrefe

  Heart rhythm : the official journal of the Heart Rhythm Society. 08/2011; 8(10):1553-4.

• Long-term follow-up of patients with short QT syndrome.

  Authors: Carla Giustetto, Rainer Schimpf, Andrea Mazzanti, Chiara Scrocco, Philippe Maury, Olli Anttonen, Vincent Probst, Jean-Jacques Blanc, Pascal Sbragia, Paola Dalmasso, Martin Borggrefe, Fiorenzo Gaita

  Journal of the American College of Cardiology. 08/2011; 58(6):587-95.

  The aim of this study was to investigate the clinical characteristics and the long-term course of a large cohort of patients with short QT syndrome (SQTS). SQTS is a rare channelopathy characterizedThe aim of this study was to investigate the clinical characteristics and the long-term course of a large cohort of patients with short QT syndrome (SQTS). SQTS is a rare channelopathy characterized by an increased risk of sudden death. Data on the long-term outcome of SQTS patients are not available. Fifty-three patients from the European Short QT Registry (75% males; median age: 26 years) were followed up for 64 ± 27 months. A familial or personal history of cardiac arrest was present in 89%. Sudden death was the clinical presentation in 32%. The average QTc was 314 ± 23 ms. A mutation in genes related to SQTS was found in 23% of the probands; most of them had a gain of function mutation in HERG (SQTS1). Twenty-four patients received an implantable cardioverter defibrillator, and 12 patients received long-term prophylaxis with hydroquinidine (HQ), which was effective in preventing the induction of ventricular arrhythmias. Patients with a HERG mutation had shorter QTc at baseline and a greater QTc prolongation after treatment with HQ. During follow-up, 2 already symptomatic patients received appropriate implantable cardioverter defibrillator shocks and 1 had syncope. Nonsustained polymorphic ventricular tachycardia was recorded in 3 patients. The event rate was 4.9% per year in the patients without antiarrhythmic therapy. No arrhythmic events occurred in patients receiving HQ. SQTS carries a high risk of sudden death in all age groups. Symptomatic patients have a high risk of recurrent arrhythmic events. HQ is effective in preventing ventricular tachyarrhythmia induction and arrhythmic events during long-term follow-up.

• Platelet and monocyte activation in acute ischemic stroke--is there a correlation with stroke etiology?

  Authors: Tom Oberheiden, Xuan Duc Nguyen, Marc Fatar, Elif Elmas, Christian Blahak, Nicole Morper, Carl Erik Dempfle, Michael Hennerici, Martin Borggrefe, Thorsten Kälsch

  Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 07/2011; 18(1):87-91.

  An upregulation of platelet CD40 ligand (CD40L) and CD62P has been described in atherosclerotic cardiovascular diseases and among patients with acute cerebral ischemia. Correlation between plateletAn upregulation of platelet CD40 ligand (CD40L) and CD62P has been described in atherosclerotic cardiovascular diseases and among patients with acute cerebral ischemia. Correlation between platelet and monocyte activation and the etiology of ischemic stroke were examined in 41 patients with acute ischemic stroke. Compared to 10 controls, all patients with stroke showed a significantly elevated platelet expression of CD40L (P < .001) and had significantly higher amounts of platelet-monocyte aggregates (P = .002). Plasma levels of interleukin 7 were significantly lower in patients with stroke compared to controls (P = .006). Patients with small artery disease had a significantly higher platelet CD40L expression than patients with cardioembolic stroke (P = .029). Plasma levels of soluble CD40L were significantly higher in patients with large artery disease compared to patients with cardioembolic stroke (P = .047). In conclusion, patients with acute ischemic stroke show an upregulation of platelet CD40L and an activation of cellular coagulation with highest activation in the large artery disease subgroup.

• A comparative evaluation of electrical velocimetry and inert gas rebreathing for the non-invasive assessment of cardiac output.

  Authors: Frederik Trinkmann, Manuel Berger, Ursula Hoffmann, Martin Borggrefe, Jens J Kaden, Joachim Saur

  Clinical research in cardiology : official journal of the German Cardiac Society. 07/2011; 100(10):935-43.

  When assessing the function of the cardiovascular system, cardiac output (CO) is a substantial parameter. For its determination, numerous non-invasive techniques have been proposed in the recentWhen assessing the function of the cardiovascular system, cardiac output (CO) is a substantial parameter. For its determination, numerous non-invasive techniques have been proposed in the recent years including inert gas rebreathing (IGR) and impedance cardiography (ICG). The aim of our study was to evaluate whether a novel ICG algorithm (electrical velocimetry) and IGR can be used interchangeably in the clinical setting. A total of 120 consecutive stable patients were included resulting in two pairs of repeated non-invasive cardiac output measurements. The mean CO was 5.0 ± 1.2 l/min (range 2.6-8.6 l/min) using IGR and 4.4 ± 1.1 l/min (1.7-7.4 l/min) using ICG, respectively. Bland-Altman analysis revealed an acceptable agreement with a mean bias of 0.6 ± 1.2 l/min. We found a high reproducibility with a mean bias of 0.2 ± 0.7 l/min for IGR and 0.0 ± 0.3 l/min for ICG (p < 0.001), respectively. There was a statistically significant difference for unphysiological circulatory conditions represented by values of 2.6-4.1 l/min and 5.6-8.6 l/min. Both non-invasive techniques are associated with low operating costs and require only a few expendable items for the rapid determination of cardiac function. We found an acceptable agreement between IGR and ICG as well as a high reproducibility, which was statistically significant higher for ICG. For cardiac output states exceeding the physiological range, we found a statistically significant difference. Consequently, values of cardiac function determined by either method should not be used interchangeably in the clinical setting.

• Effects of nicotinic acid on endothelial cells and platelets.

  Authors: Ksenija Stach, Friederike Zaddach, Xuan Duc Nguyen, Elif Elmas, Stefan Kralev, Christel Weiß, Martin Borggrefe, Thorsten Kälsch

  Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. 05/2011; 21(2):89-95.

  BACKGROUND: Interactions between platelets and endothelial cells under inflammatory conditions lead to an increased expression of various activity markers of atherosclerosis in the vessel wall. TheBACKGROUND: Interactions between platelets and endothelial cells under inflammatory conditions lead to an increased expression of various activity markers of atherosclerosis in the vessel wall. The purpose of this study was to investigate possible protective effects of nicotinic acid in an in vitro endothelial cell model. METHODS: After a 24-hour incubation period with nicotinic acid (1 mmol/l), human umbilical vein endothelial cells were stimulated for 1 h with lipopolysaccharide and were then incubated in direct contact with activated platelets. Following this incubation, the expression of CD40L and CD62P on platelets and the expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, uPAR, and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analyzed by ELISA for soluble MCP-1 and MMP-1. RESULTS: The increased expression of VCAM-1 on endothelial cells by proinflammatory stimulation with activated platelets was significantly reduced through preincubation with nicotinic acid (P<.05). Furthermore, platelets in direct contact with preincubated endothelial cells showed a significant reduction in their CD62P and CD40L expression when compared to platelets incubated with untreated endothelial cells (P<.05). Treatment with nicotinic acid did not have a significant effect on ICAM-1, uPAR, and MT1-MMP expression on endothelial cells. Levels of soluble MCP-1 and MMP-1 in supernatants were lower after preincubation with nicotinic acid. CONCLUSION: Nicotinic acid inhibits platelet activation after platelets contacted nicotinic acid treated endothelial cells and inhibits VCAM-1 expression on human endothelial cells under inflammatory conditions. These findings suggest a possible pleiotropic therapeutic relevance of nicotinic acid in atherosclerosis.

• No evidence for an association between the rs2824292 variant at chromosome 21q21 and ventricular fibrillation during acute myocardial infarction in a German population.

  Authors: Peter Bugert, Elif Elmas, Ksenija Stach, Christel Weiss, Thorsten Kälsch, Dobromir Dobrev, Martin Borggrefe

  Clinical chemistry and laboratory medicine : CCLM / FESCC. 05/2011; 49(7):1237-9.

  In a recently published genome-wide association study (GWAS), three single nucleotide polymorphisms (SNPs) (rs2824292, rs1353342, rs12090554) were significantly associated with increasedIn a recently published genome-wide association study (GWAS), three single nucleotide polymorphisms (SNPs) (rs2824292, rs1353342, rs12090554) were significantly associated with increased susceptibility for ventricular fibrillation (VF) during acute myocardial infarction (AMI). The association of rs2824292 could be confirmed in a second cohort. Both cohorts were from the Netherlands. We aimed to replicate this association in a German cohort of AMI patients with or without VF. We included a German cohort of 90 individuals with AMI and VF (cases) and 167 AMI individuals without VF and used Taqman assays for SNP typing. None of the loci showed evidence for a statistically significant association with VF. The observed genotype frequencies of the three loci were in Hardy-Weinberg equilibrium, which essentially excludes genotyping errors. In contrast to the data from the Netherlands, we could not detect a significant association of the rs2824292 locus and risk of VF during AMI in our German cohort. Differences in recruitment and clinical phenotypes between the Dutch and German cohorts may underlie different genotype associations.

• Global and regional myocardial function quantification in Takotsubo cardiomyopathy in comparison to acute anterior myocardial infarction using two-dimensional (2D) strain echocardiography.

  Authors: Felix Heggemann, Karsten Hamm, Thorsten Kaelsch, Tim Sueselbeck, Theano Papavassiliu, Martin Borggrefe, Dariusch Haghi

  Echocardiography (Mount Kisco, N.Y.). 05/2011; 28(7):715-9.

  This study sought to compare global and regional myocardial function in Takotsubo cardiomyopathy (TC) to that in acute anterior myocardial infarction (AMI) using 2D strain imaging. Twelve consecutiveThis study sought to compare global and regional myocardial function in Takotsubo cardiomyopathy (TC) to that in acute anterior myocardial infarction (AMI) using 2D strain imaging. Twelve consecutive patients with TC (ten women, two men) and 12 patients with AMI (four women, eight men) underwent 2D echocardiography at initial presentation. 2D strain images were analyzed to measure longitudinal and radial strain. Global strain was calculated as the average longitudinal strain of the segments of two-, three-, and four-chamber views. Biplane ejection fraction was assessed using Simpson's biplane method. Significant differences in radial strain (TC vs. AMI) were found in lateral (13.5 ± 10.1% vs. 25.1 ± 11.2%, P = 0.035), posterior (15.2 ± 14.5% vs. 51.4 ± 14.2%, P < 0.001), and inferior (17.9 ± 15.5% vs. 49.4 ± 16.9%, P = 0.002) segments. Longitudinal strain was significantly lower in TC in basal-inferior (-15.8 ± 9.2% vs. -22.7 ± 3.8%, P = 0.037), midinferior (-8.3 ± 9.2% vs. -16.8 ± 3.0%, P = 0.004), basal-posterior (-12.2 ± 9.4% vs. -21.6 ± 4.4%, P = 0.016), midposterior (-4.4 ± 8.0% vs. -15.4 ± 3.5%, P = 0.002), apical-posterior (2.3 ± 6.7% vs. -6.4 ± 10.1%, P = 0.023), and midlateral (-3.4 ± 6.9% vs. -9.5 ± 5.8%, P = 0.028) segments. Global strain and ejection fraction were significantly higher in patients with AMI (-3.5 ± 8.2% vs. -10.3 ± 8.4%, P < 0.001 and 37 ± 11% vs. 46 ± 11%, P = 0.045). In TC, strain was reduced around the entire mid left-ventricular circumference, whereas in AMI it was predominantly reduced in the anterior and anteroseptal wall. These observed differences confirm the notion that TC affects myocardium beyond the territory of a single coronary artery. They may allow noninvasive distinction between both entities.

• Midregional pro-atrial natriuretic peptide: a novel marker of myocardial fibrosis in patients with hypertrophic cardiomyopathy.

  Authors: Elif Elmas, Christina Doesch, Stephan Fluechter, Miriam Freundt, Christel Weiss, Siegfried Lang, Thorsten Kälsch, Dariush Haghi, Jana Papassotiriou, Jan Kunde, Stefan O Schoenberg, Martin Borggrefe, Theano Papavassiliu

  The international journal of cardiovascular imaging. 04/2011; 27(4):547-56.

  We aimed to determine the diagnostic performance of biomarkers in predicting myocardial fibrosis assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) inWe aimed to determine the diagnostic performance of biomarkers in predicting myocardial fibrosis assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) in patients with hypertrophic cardiomyopathy (HCM). LGE CMR was performed in 40 consecutive patients with HCM. Left and right ventricular parameters, as well as the extent of LGE were determined and correlated to the plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), carboxy-terminal pro-vasopressin (CT-proAVP), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8). Myocardial fibrosis was assumed positive, if CMR indicated LGE. LGE was present in 26 of 40 patients with HCM (65%) with variable extent (mean: 14%, range: 1.3-42%). The extent of LGE was positively associated with MR-proANP (r = 0.4; P = 0.01). No correlations were found between LGE and MR-proADM (r = 0.1; P = 0.5), CT-proET-1 (r = 0.07; P = 0.66), CT-proAVP (r = 0.16; P = 0.3), MMP-9 (r = 0.01; P = 0.9), TIMP-1 (r = 0.02; P = 0.85), and IL-8 (r = 0.02; P = 0.89). After adjustment for confounding factors, MR-proANP was the only independent predictor associated with the presence of LGE (P = 0.007) in multivariate analysis. The area under the ROC curve (AUC) indicated good predictive performance (AUC = 0.882) of MR-proANP with respect to LGE. The odds ratio was 1.268 (95% confidence interval 1.066-1.508). The sensitivity of MR-proANP at a cut-off value of 207 pmol/L was 69%, the specificity 94%, the positive predictive value 90% and the negative predictive value 80%. The results imply that MR-proANP serves as a novel marker of myocardial fibrosis assessed by LGE CMR in patients with HCM.

• Arrhythmias: a ‘Schwartz score’ for short QT syndrome.

  Authors: Christian Veltmann, Martin Borggrefe

  Nature reviews. Cardiology. 03/2011; 8(5):251-2.

• Platelet and monocyte activity markers and mediators of inflammation in Takotsubo cardiomyopathy.

  Authors: Rainer Pirzer, Elif Elmas, Dariusch Haghi, Christiane Lippert, Stefan Kralev, Siegfried Lang, Martin Borggrefe, Thorsten Kälsch

  Heart and vessels. 03/2011;

  Patients with Takotsubo cardiomyopathy (TC) often present with symptoms similar to those of myocardial infarction (MI). We analyzed blood concentrations of mediators of inflammation and platelet- andPatients with Takotsubo cardiomyopathy (TC) often present with symptoms similar to those of myocardial infarction (MI). We analyzed blood concentrations of mediators of inflammation and platelet- and monocyte-activity markers in patients with TC and MI for significant differences. Clinical data of patients with TC (n = 16) and acute MI (n = 16) were obtained. Serial blood samples were taken at the time of hospital admission (t (0)), after 2-4 days (t (1)) and after 4-7 weeks (t (2)), respectively. Plasma concentrations of interleukin (IL)-6, IL-7, soluble CD40 ligand (sCD40L), and monocyte chemotactic protein 1 (MCP-1) were determined with an ELISA. Tissue factor binding on monocytes, platelet-activation marker CD62P, platelet CD40-ligand (CD40L), and platelet-monocyte aggregates were measured using flow cytometry. Expression of CD62P on platelets and IL-6 plasma levels were significantly lower in patients with TC compared to MI at the time of hospital admission. IL-7 plasma levels were significantly elevated in patients with TC compared to patients with MI at 2-4 days after hospital admission. No significant differences were observed concerning sCD40L and MCP-1 plasma levels, tissue factor binding on monocytes, CD40L expression on platelets, and platelet-monocyte aggregates at any point in time. Our results indicate that inflammatory mediators and platelet-activity markers contribute to the differences in the pathogenesis of MI and TC.

• Sudden cardiac death in a patient with lamin A/C mutation in the absence of dilated cardiomyopathy or conduction disease.

  Authors: Philipp Ehlermann, Stephanie Lehrke, Theano Papavassiliu, Benjamin Meder, Martin Borggrefe, Hugo A Katus, Rainer Schimpf

  Clinical research in cardiology : official journal of the German Cardiac Society. 02/2011; 100(6):547-51.

• Incidence and severity of coronary artery disease in patients with atrial fibrillation undergoing first-time coronary angiography.

  Authors: Stefan Kralev, Kathrin Schneider, Siegfried Lang, Tim Süselbeck, Martin Borggrefe

  PloS one. 01/2011; 6(9):e24964.

  In standard reference sources, the incidence of coronary artery disease (CAD) in patients with atrial fibrillation (AF) ranged between 24 and 46.5%. Since then, the incidence of cardiovascular riskIn standard reference sources, the incidence of coronary artery disease (CAD) in patients with atrial fibrillation (AF) ranged between 24 and 46.5%. Since then, the incidence of cardiovascular risk factors (CRF) has increased and modern treatment strategies ("pill in the pocket") are only applicable to patients without structural heart disease. The aim of this study was to investigate the incidence and severity of CAD in patients with AF. From January 2005 until December 2009, we included 261 consecutive patients admitted to hospital with paroxysmal, persistent or permanent AF in this prospective study. All patients underwent coronary angiography and the Framingham risk score (FRS) was calculated. Patients with previously diagnosed or previously excluded CAD were excluded. The overall incidence of CAD in patients presenting with AF was 34%; in patients >70 years, the incidence of CAD was 41%. The incidence of patients undergoing a percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) was 21%. Patients with CAD were older (73±8 years vs 68±10 years, p = 0.001), had significantly more frequent hypercholesterolemia (60% vs 30%, p<0.001), were more frequent smokers (26% vs 13%, p = 0.017) and suffered from angina more often (37% vs 2%, p<0.001). There was a significant linear trend among the FRS categories in percentage and the prevalence of CAD and PCI/CABG (p<0.0001). The overall incidence of CAD in patients presenting with AF was relatively high at 34%; the incidence of PCI/CABG was 21%. Based upon increasing CRF in the western world, we recommend a careful investigation respecting the FRS to either definitely exclude or establish an early diagnosis of CAD--which could contribute to an early and safe therapeutic strategy considering type Ic antiarrhythmics and oral anticoagulation.