Publications by authors named "Johannes Steinfurt"

21 Publications

  • Page 1 of 1

Catheter ablation of short-coupled variant of torsade de pointes.

Clin Res Cardiol 2021 Mar 26. Epub 2021 Mar 26.

Department of Cardiology and Angiology, Märkische Kliniken GmbH, Klinikum Luedenscheid, Luedenscheid, Germany.

Background: The short-coupled variant of torsade de pointes (sc-TdP) is a malignant arrhythmia that frequently presents with ventricular fibrillation (VF) electrical storm. Verapamil is considered the first-line therapy of sc-TdP while catheter ablation is not widely adopted. The aim of this study was to determine the origin of sc-TdP and to assess the outcome of catheter ablation using 3D-mapping.

Methods And Results: We retrospectively analyzed five patients with sc-TdP who underwent 3D-mapping and ablation of sc-TdP at five different institutions. Four patients initially presented with sudden cardiac arrest, one patient experienced recurrent syncope as the first manifestation. All patients demonstrated a monomorphic premature ventricular contraction (PVC) with late transition left bundle branch block pattern, superior axis, and a coupling interval of less than 300 ms. triggering recurrent TdP and VF. In four patients, the culprit PVC was mapped to the free wall insertion of the moderator band (MB) with a preceding Purkinje potential in two patients. Catheter ablation using 3D-mapping and intracardiac echocardiography eliminated sc-TdP in all patients, with no recurrence at mean 2.7 years (range 6 months to 8 years) of follow-up.

Conclusion: 3D-mapping and intracardiac echocardiography demonstrate that sc-TdP predominantly originates from the MB free wall insertion and its Purkinje network. Catheter ablation of the culprit PVC at the MB free wall junction leads to excellent short- and long-term results and should be considered as first-line therapy in recurrent sc-TdP or electrical storm.
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http://dx.doi.org/10.1007/s00392-021-01840-zDOI Listing
March 2021

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

Mahaim pathway potential revealed by high-resolution three-dimensional mapping.

Herzschrittmacherther Elektrophysiol 2020 Dec 28;31(4):437-440. Epub 2020 Sep 28.

Department of Cardiology and Angiology, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.

Mapping and ablation of atriofascicular fibers can be highly challenging due to the complex and dynamic anatomy of the tricuspid valve annulus. This case highlights the utility of a multi-electrode catheter three-dimensional mapping approach to localize the Mahaim pathway along the tricuspid annulus in order to guide catheter ablation.
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http://dx.doi.org/10.1007/s00399-020-00721-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683446PMC
December 2020

Impact of Preprocedural Aortic Valve Calcification on Conduction Disturbances after Transfemoral Aortic Valve Replacement.

Cardiology 2021 23;146(2):228-237. Epub 2020 Sep 23.

University Heart Center Freiburg, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Aim: The present study analyzes in depth the impact of different calcification patterns on disturbances of the conduction system in transcatheter aortic valve replacement (TAVR) patients.

Methods And Results: A total of 169 preprocedural TAVR multislice computed tomography scans from consecutive transfemoral (TF) TAVRs performed between 2014 and 2017 using either Edwards SAPIEN or Medtronic Evolut R valves were retrospectively evaluated. The volume, distribution, and orientation of annular and valvular aortic valve calcification were measured and their impact on postoperative conduction disturbances was determined using linear and logistic regression analyses. The total volume of calcification and distribution at the aortic annulus or valve did not influence the conduction system. Oval calcification of the left aortic cusp was independently associated with an elevated risk for an increase in atrioventricular block degree (+0.6, p = 0.03). Moreover, orthogonal calcifications at the level of the aortic annulus were associated with an increased risk for QRS prolongation (+26 ms, p = 0.004) and an increased risk for permanent pacemaker implantation (OR 4.3, p = 0.03) after TF TAVR. This was more pronounced in patients undergoing TF TAVR using a balloon-expandable Edwards SAPIEN 3 valve (QRS +38.195 ms, p < 0.001; OR permanent pacemaker 15.48, p = 0.013).

Conclusion: Orthogonal annular calcification confers an increased risk for conduction disturbances after TAVR. This is even more pronounced after implantation of balloon-expandable valves.
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http://dx.doi.org/10.1159/000509389DOI Listing
September 2020

Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

Genet Med 2021 Jan 7;23(1):47-58. Epub 2020 Sep 7.

Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.

Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.

Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.

Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.

Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
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http://dx.doi.org/10.1038/s41436-020-00946-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790744PMC
January 2021

One-Year Course of Periprocedural Anticoagulation in Atrial Fibrillation Ablation: Results of a German Nationwide Survey.

Cardiology 2020 27;145(10):676-681. Epub 2020 Aug 27.

Cardiac Arrhythmia Service, Division of Cardiology, Pulmonology and Vascular Medicine, Faculty of Medicine, Heinrich-Heine University, Düsseldorf, Germany.

Introduction: Periprocedural oral anticoagulation (OAC) strategies for atrial fibrillation (AF) ablation procedures are changing rapidly.

Objective: To assess the management and course of periprocedural OAC for AF ablation procedures in experienced electrophysiology (EP) centers in Germany over the last 12 months.

Methods: The data are based on an electronic questionnaire, which was sent to 35 experienced EP centers in September 2018 and then exactly 1 year later. Participants provided information on their periprocedural OAC management, the handling with dual therapy (OAC plus single antiplatelet therapy), the availability of specific antidotes, the transseptal puncture approach, and noteworthy complications.

Results: Responses were received from all 35 centers and represent 10,010 AF ablation procedures annually. In 2018, the administration of vitamin K antagonist (VKA) was continued throughout the procedure at all centers (100%). In contrast, the majority of centers used minimally interrupted periprocedural non-vitamin K antagonist oral anticoagulants (NOAC) (54.3%), 13 centers (37.2%) completely interrupted NOAC, and only 3 centers (8.5%) continued NOAC throughout the procedure. At the 1-year follow-up survey, 32 centers were found to have continued their previous strategy of periprocedural OAC and 3 changed from a minimally interrupted to a continued NOAC strategy. Of note, 30 centers (85.7%) performed transseptal puncture fluoroscopically without additional cardiac imaging. In the setting of uninterrupted periprocedural OAC management, no relevant complications were noted.

Conclusion: Our survey shows marked heterogeneous periprocedural OAC management at experienced EP centers in Germany. Whereas continuation of VKA has already been integrated into clinical practice, the majority of centers still use a minimally interrupted NOAC strategy.
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http://dx.doi.org/10.1159/000509399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592950PMC
August 2020

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome.

Circulation 2020 Jul 20;142(4):324-338. Epub 2020 May 20.

Masonic Medical Research Institute, Utica, NY (R.P.).

Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility.

Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score.

Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (<5×10) near , , and , and 1 missense variant in (p.Asp85Asn) at the suggestive threshold (<10). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation ( 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r=0.40; =3.2×10). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (<0.005).

Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.045956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382531PMC
July 2020

Extracellular HtrA2 Induces Apoptosis in Human Umbilical Vein Endothelial Cells.

Int J Mol Sci 2019 Oct 31;20(21). Epub 2019 Oct 31.

Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg 79106, Germany.

The serine protease high-temperature-required protein A2 (HtrA2) has been identified as a key intracellular molecule promoting apoptosis in cells during ischemia reperfusion (IR) injury. IR injury in ST-segment elevation myocardial infarction (STEMI) contributes to overall myocardial damage. HtrA2 has further been shown to be significantly increased in the serum of patients with STEMI. In the present pilot study, we use human umbilical vein endothelial cells (HUVECs) to investigate whether extracellular HtrA2 induces apoptosis using Annexin V staining. Furthermore, we examine whether HtrA2 is released extracellularly after staurosporine-induced apoptosis using ELISA. We find that HtrA2 is released upon induction of apoptosis by staurosporine into the cell culture medium. Furthermore, treatment of HUVECs with extracellular HtrA2-induces apoptosis, while the addition of anti-HtrA2 antibodies reduces both HtrA2- and staurosporine-induced endothelial cell apoptosis. In conclusion, we show here that extracellular HtrA2 induces apoptosis in human endothelial cells, although the exact molecular mechanisms have to be investigated in future.
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http://dx.doi.org/10.3390/ijms20215446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862081PMC
October 2019

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

[Pacemaker and ICD electrocardiograms].

Herzschrittmacherther Elektrophysiol 2019 Mar 1;30(1):11-23. Epub 2019 Mar 1.

Universitäres Herzzentrum Hamburg (UHZ), Klinik für Kardiologie mit Schwerpunkt Elektrophysiologie, Universitätsklinikum Hamburg Eppendorf, Hamburg, Deutschland.

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http://dx.doi.org/10.1007/s00399-019-0610-6DOI Listing
March 2019

Transgenic short-QT syndrome 1 rabbits mimic the human disease phenotype with QT/action potential duration shortening in the atria and ventricles and increased ventricular tachycardia/ventricular fibrillation inducibility.

Eur Heart J 2019 03;40(10):842-853

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

Aims: Short-QT syndrome 1 (SQT1) is an inherited channelopathy with accelerated repolarization due to gain-of-function in HERG/IKr. Patients develop atrial fibrillation, ventricular tachycardia (VT), and sudden cardiac death with pronounced inter-individual variability in phenotype. We generated and characterized transgenic SQT1 rabbits and investigated electrical remodelling.

Methods And Results: Transgenic rabbits were generated by oocyte-microinjection of β-myosin-heavy-chain-promoter-KCNH2/HERG-N588K constructs. Short-QT syndrome 1 and wild type (WT) littermates were subjected to in vivo ECG, electrophysiological studies, magnetic resonance imaging, and ex vivo action potential (AP) measurements. Electrical remodelling was assessed using patch clamp, real-time PCR, and western blot. We generated three SQT1 founders. QT interval was shorter and QT/RR slope was shallower in SQT1 than in WT (QT, 147.8 ± 2 ms vs. 166.4 ± 3, P < 0.0001). Atrial and ventricular refractoriness and AP duration were shortened in SQT1 (vAPD90, 118.6 ± 5 ms vs. 154.4 ± 2, P < 0.0001). Ventricular tachycardia/fibrillation (VT/VF) inducibility was increased in SQT1. Systolic function was unaltered but diastolic relaxation was enhanced in SQT1. IKr-steady was increased with impaired inactivation in SQT1, while IKr-tail was reduced. Quinidine prolonged/normalized QT and action potential duration (APD) in SQT1 rabbits by reducing IKr. Diverse electrical remodelling was observed: in SQT1, IK1 was decreased-partially reversing the phenotype-while a small increase in IKs may partly contribute to an accentuation of the phenotype.

Conclusion: Short-QT syndrome 1 rabbits mimic the human disease phenotype on all levels with shortened QT/APD and increased VT/VF-inducibility and show similar beneficial responses to quinidine, indicating their value for elucidation of arrhythmogenic mechanisms and identification of novel anti-arrhythmic strategies.
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http://dx.doi.org/10.1093/eurheartj/ehy761DOI Listing
March 2019

A novel LMNA nonsense mutation causes two distinct phenotypes of cardiomyopathy with high risk of sudden cardiac death in a large five-generation family.

Europace 2018 12;20(12):2003-2013

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

Aims: Characterization of the cardiac phenotype associated with the novel LMNA nonsense mutation c.544C>T, p.Q182*, which we have identified in a large five-generation family.

Methods And Results: A family tree was constructed. Clinical data [arrhythmia, syncope, sudden cardiac death (SCD), New York Heart Association (NYHA) class] were collected from living and deceased family members. DNA of 23 living family members was analysed for mutations in LMNA. Additionally, dilated cardiomyopathy multi-gene-panel testing and whole exome sequencing were performed in some family members to identify potential phenotype-modifiers. In this five-generation family (n = 65), 17 SCDs occurred at 49.3 ± 10.0 years. Furthermore, we identified eight additional mutation-carriers, seven symptomatic (44 ± 13 years), and one asymptomatic (44 years). First signs of disease [sinus bradycardia with atrioventricular (AV)-block I°] occurred at 36.5 ± 8.1 years. Paroxysmal atrial fibrillation (AF) (onset at 41.8 ± 5.7 years) rapidly progressed to permanent AF (46.2 ± 9.8 years). Subsequently, AV-conduction worsened, syncope, pacemaker-dependence, and non-sustained ventricular tachycardia (43.3 ± 8.2 years) followed. Ventricular arrhythmia caused SCD in patients without implantable cardioverter-defibrillator (ICD). Patients protected by ICD developed rapidly progressive heart failure (45.2 ± 10.6 years). A different phenotype was seen in a sub-family in three patients with early onset of rapidly decompensating heart failure and only minor prior arrhythmia-related symptoms. One patient received high-urgency heart transplantation (HTX) at 32 years, while two died prior to HTX. One of them developed lethal peripartum-associated heart failure. Possible disease-modifiers were identified in this 'heart failure sub-family'.

Conclusion: The novel LMNA nonsense mutation c.544C>T causes a severe arrhythmogenic phenotype manifesting with high incidence of SCD in most patients; and in one sub-family, a distinct phenotype with fast progressing heart failure, indicating the need for early consideration of ICD-implantation and listing for heart-transplantation.
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http://dx.doi.org/10.1093/europace/euy127DOI Listing
December 2018

Catheter Ablation of Brugada Syndrome: Importance of Repeated Administration of Ajmaline to Unmask the Entire Epicardial Substrate.

JACC Clin Electrophysiol 2017 Nov 26;3(11):1330-1332. Epub 2017 Apr 26.

Department of Internal Medicine and Cardiology, Unfallkrankenhaus Berlin, Berlin, Germany.

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http://dx.doi.org/10.1016/j.jacep.2017.02.014DOI Listing
November 2017

Staphylococcus aureus bacteremia with iliac artery endarteritis in a patient receiving ustekinumab.

BMC Infect Dis 2016 10 20;16(1):586. Epub 2016 Oct 20.

Division of Infectious Diseases, Department of Medicine II, University Medical Center Freiburg, Hugstetter Str. 55, Freiburg, 79106, Germany.

Background: Ustekinumab (Stelara®), a human monoclonal antibody targeting the p40-subunit of interleukin (IL)-12 and IL-23, is indicated for moderate to severe plaque psoriasis and psoriatic arthritis. In large multicenter, prospective trials assessing efficacy and safety of ustekinumab increased rates of severe infections have not been observed so far.

Case Presentation: Here, we report the case of a 64-year old woman presenting with chills, pain and swelling of her right foot with dark maculae at the sole, and elevated inflammatory markers. She had received a third dose of ustekinumab due to psoriatic arthritis three days before admission. Blood cultures revealed growth of Staphylococcus aureus and imaging showed a thickening of the aortic wall ventral the bifurcation above the right internal iliac artery, resembling an acute bacterial endarteritis. Without the evidence of aneurysms and in absence of foreign bodies, the decision for conservative management was made. The patient received four weeks of antibiotic therapy with intravenous flucloxacillin, followed by an oral regime with levofloxacin and rifampicin for an additional four weeks. Inflammatory markers resolved promptly and the patient was discharged in good health.

Conclusion: To our knowledge, this is the first report of a severe S. aureus infection in a patient receiving ustekinumab. Albeit ustekinumab is generally regarded as a safe drug, severe bacterial infections should always be included in the differential diagnosis of elevated inflammatory markers in patients receiving biologicals as these might present with nonspecific symptoms and fever might be absent. Any effort to detect deep-seated or metastatic infections should be made to prevent complications and to secure appropriate treatment. Although other risk factors for an invasive staphylococcal infection like psoriasis, recent corticosteroid injection, or prior hospitalisations were present, and therefore a directive causative link between the S. aureus bacteraemia and ustekinumab can not be drawn, we considered the reporting of this case worthwhile to alert clinicians as we believe that ongoing pharmacovigilance to detect increased risks for rare but severe infections beyond phase II and phase III trials in patients treated with biologicals is essential.
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http://dx.doi.org/10.1186/s12879-016-1912-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072319PMC
October 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.
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http://dx.doi.org/10.3238/arztebl.2015.0394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498009PMC
June 2015

High-dose flecainide with low-dose β-blocker therapy in catecholaminergic polymorphic ventricular tachycardia: A case report and review of the literature.

J Cardiol Cases 2015 Jan 26;11(1):10-13. Epub 2014 Sep 26.

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

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by recurrent syncopes and sudden cardiac death triggered by sympathetic activation in young individuals without structural heart disease and a normal baseline electrocardiogram. There is reason to question whether the current expert consensus treatment recommendation, tolerated β-blockade alone or in combination with low-dose flecainide, is the antiarrhythmic treatment strategy in CPVT, as high doses of β-blockers may eventually lead to adverse side effects and β-blocker discontinuation. Indeed, β-blocker non-compliance accounts for around 5% of sudden cardiac deaths in CPVT patients.

Case Report: Differing from the current recommendation, we present the first report of a CPVT patient successfully treated with high-dose flecainide and β-blockade. This combination resulted in complete suppression of ventricular arrhythmias during exercise stress tests and Holter monitoring and was well tolerated without any side effects. We review the current literature on β-blocker non-compliance-related sudden cardiac death in CPVT, summarize the and data on flecainide therapy in CPVT, and discuss the rationale of our antiarrhythmic approach.< This case illustrates typical features of CPVT including the therapeutic management of a young CPVT patient with poor β-blocker tolerance at normal dosages. In this setting, high-dose flecainide combined with β-blockade may (1) result in complete antiarrhythmic response and may (2) improve the antiarrhythmic drug-compliance thereby reducing the risk of non-compliance-related sudden cardiac death.>.
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http://dx.doi.org/10.1016/j.jccase.2014.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279992PMC
January 2015

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:

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

[Pareses, myalgias, and massive CK elevation: a severe neurological disorder?].

Med Klin (Munich) 2010 Jul 30;105(7):496-500. Epub 2010 Jul 30.

Abteilung für Innere Medizin, Loretto-Krankenhaus, Freiburg, Germany.

Case Report: The authors report on a 51-year-old patient with transient pareses, myalgias, and a massive creatine kinase elevation which had led to an intensive neurological work-up by the general practitioner. Despite refractory hypertension, primary aldosteronism was not excluded. At the authors' clinic, the patient was diagnosed to have Conn's syndrome. Laparoscopic adrenalectomy revealed a big adenoma of the left adrenal gland.

Conclusion: Transient pareses, myalgias, and creatine kinase elevation can indicate primary aldosteronism among hypertensive patients. If clinically suspected, the aldosterone-renin ratio should be determined.
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http://dx.doi.org/10.1007/s00063-010-1084-9DOI Listing
July 2010

Autonomic modulation and antiarrhythmic therapy in a model of long QT syndrome type 3.

Cardiovasc Res 2010 Jul 28;87(1):60-72. Epub 2010 Jan 28.

Department of Cardiology and Angiology, University Hospital Münster, Albert-Schweitzer-Street 33, D-48129 Münster, Germany.

Aims: Clinical observations in patients with long QT syndrome carrying sodium channel mutations (LQT3) suggest that bradycardia caused by parasympathetic stimulation may provoke torsades de pointes (TdP). Beta-adrenoceptor blockers appear less effective in LQT3 than in other forms of the disease.

Methods And Results: We studied effects of autonomic modulation on arrhythmias in vivo and in vitro and quantified sympathetic innervation by autoradiography in heterozygous mice with a knock-in deletion (DeltaKPQ) in the Scn5a gene coding for the cardiac sodium channel and increased late sodium current (LQT3 mice). Cholinergic stimulation by carbachol provoked bigemini and TdP in freely roaming LQT3 mice. No arrhythmias were provoked by physical stress, mental stress, isoproterenol, or atropine. In isolated, beating hearts, carbachol did not prolong action potentials per se, but caused bradycardia and rate-dependent action potential prolongation. The muscarinic inhibitor AFDX116 prevented effects of carbachol on heart rate and arrhythmias. beta-Adrenoceptor stimulation suppressed arrhythmias, shortened rate-corrected action potential duration, increased rate, and minimized difference in late sodium current between genotypes. Beta-adrenoceptor density was reduced in LQT3 hearts. Acute beta-adrenoceptor blockade by esmolol, propranolol or chronic propranolol in vivo did not suppress arrhythmias. Chronic flecainide pre-treatment prevented arrhythmias (all P < 0.05).

Conclusion: Cholinergic stimulation provokes arrhythmias in this model of LQT3 by triggering bradycardia. beta-Adrenoceptor density is reduced, and beta-adrenoceptor blockade does not prevent arrhythmias. Sodium channel blockade and beta-adrenoceptor stimulation suppress arrhythmias by shortening repolarization and minimizing difference in late sodium current.
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http://dx.doi.org/10.1093/cvr/cvq029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883895PMC
July 2010