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January 2009 - present
Publications
Publications (111)
Cardiac device therapy provides not only treatment options for bradyarrhythmia but also advanced treatment for heart failure and preventive measures against sudden cardiac death. In heart failure treatment it enables synergistic reverse remodelling and reduces pharmacological side effects. Cardiac resynchronization therapy (CRT) has revolutionized...
Background
Electroanatomical mapping (EAM)-guided stereotactic arrhythmia radioablation (STAR) is a novel noninvasive therapy option for patients with monomorphic ventricular tachycardia (VT) refractory to antiarrhythmic drugs and/or urgent catheter ablation (CA). Data on success rates in an emergency situation such as electrical storm (ES) are rar...
Background
Single-session cardiac stereotactic radiation therapy (SBRT) has demonstrated promising results for patients with refractory ventricular tachycardia (VT). However, the full safety profile of this novel treatment remains unknown and very limited data from prospective clinical multicenter trials are available.
Methods
The prospective mult...
Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): RAVENTA is part of the EU-Horizon-2020 STOPSTORM project.
Background
Ventricular arrhythmias are a leading cause of morbidity and mortality in patients with structural heart disease. Non-invasive stereotactic single-fraction arrhythmia radioabla...
Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): The multicenter RAdiosurgery for VENtricular TAchycardia (RAVENTA) study (NCT03867747) is part of the STOPSTORM.eu consortium project
Background
Stereotactic Arrhythmia Radioablation (STAR) has been shown to be a promising treatment option for r...
Funding Acknowledgements
Type of funding sources: None.
Background
The safety and efficacy of the subcutaneous implantable cardioverter-defibrillator (S-ICD) has been proven in various clinical trials. Due to intermuscular device placement, higher shock energy is required for effective treatment of ventricular tachyarrhythmia. High shock impedance...
The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a po...
Background:
A variant in the SLC4A3 anion exchanger has been identified as a novel cause of short QT syndrome (SQTS), but the clinical importance of SLC4A3 as a cause of SQTS or sudden cardiac death (SCD) remains unknown.
Objective:
To investigate the prevalence of potential disease-causing variants using gene panels including SLC4A3.
Methods:...
A novel quality assurance process for electroanatomical mapping (EAM)-to-radiotherapy planning imaging (RTPI) target transport was assessed within the multi-center multi-platform framework of the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial. A stand-alone software (CARDIO-RT) was developed to enable platform independent registration of...
A novel quality assurance process for electroanatomical mapping (EAM)-to-radiotherapy planning imaging (RTPI) target transport was assessed within a multi-center multi-platform framework. A stand-alone software (CARDIO-RT) was developed to enable platform independent registration of EAM and RTPI of the left ventricle (LV), based on pre-generated ra...
We hypothesized that myocardial septal scarring, assessed by cardiac magnetic resonance (CMR) using late gadolinium enhancement (LGE), at the site of cardiac contractility modulation (CCM) lead placement may predict treatment response. Eligible heart failure (HF) patients underwent LGE CMR imaging before CCM device implantation. The response to CCM...
Background
Ventricular tachycardia (VT) is a potentially life-threatening heart rhythm disorder originating in heterogeneous conduction velocity in the ventricular myocardium, e.g. by scar formation in ischaemic or dilated cardiomyopathy. Current guideline-directed medical therapy comprises implantable cardioverter defibrillator (ICD), antiarrhythm...
Background
Cardiac contractility modulation (CCM) is an FDA-approved device therapy for patients with medication refractory systolic heart failure and normal QRS width. Pivotal trials have been performed primarily in patients with advanced heart failure (NYHA class III or ambulatory IV). As observed in clinical practice, CCM might also be beneficia...
Background
Cardiac contractility modulation (CCM) is an FDA-approved device therapy for patients with refractory systolic heart failure and normal QRS width. Randomized trials demonstrated benefits of CCM primarily for patients with severe heart failure (> NYHA class II).PurposeTo better understand individualized indication in clinical practice, we...
Background
Males with X-linked recessive spinobulbar muscular atrophy (SBMA) are reported to die suddenly and a Brugada electrocardiography (ECG) pattern may be present. A hallmark of this pattern is the presence of ST segment elevations in right precordial leads associated with an increased risk of sudden cardiac death.
Objective
We aimed to dete...
Purpose
In the beam penumbra of stereotactic body radiotherapy volumes, dose rate effects in implantable cardioverter–defibrillators (ICDs) may be the predominant cause for failures in the absence of neutron-generating photon energies. We investigate such dose rate effects in ICDs and provide evidence for safe use of lung tumor stereotactic radioab...
Purpose
Cardiac radioablation is a novel treatment option for patients with refractory ventricular tachycardia (VT) unsuitable for catheter ablation. The quality of treatment planning depends on dose specifications, platform capabilities, and experience of the treating staff. To harmonize the treatment planning, benchmarking of this process is nece...
Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and ident...
Background:
Cardiac contractility modulation (CCM), being reserved for patients with symptomatic chronic heart failure (HF) and narrow QRS complex under guideline directed medical therapy, can recover initially reduced left ventricular ejection fraction (LVEF); however, the influence of pre-implantation LVEF on long-term outcomes is not fully unde...
Aims:
The aim of this study was to evaluate the prognostic value of feature tracking (FT) derived cardiac magnetic resonance (CMR) strain parameters of the left ventricle (LV)/right ventricle (RV) in ischaemic cardiomyopathy (ICM) patients treated with an implantable cardioverter-defibrillator (ICD). Current guidelines suggest a LV-ejection fracti...
Background:
Ventricular tachycardia (VT) is a potentially lethal complication of structural heart disease. Despite optimal management, a subgroup of patients continue to suffer from recurrent VT. Recently, cardiac stereotactic body radiotherapy (CSBRT) has been introduced as a treatment option in patients with VT refractory to antiarrhythmic drugs...
Background:
Cardiac contractility modulation (CCM) is an FDA-approved device-based therapy for patients with systolic heart failure and normal QRS complex who are symptomatic despite optimal drug therapy. The purpose of this study was to compare the long-term therapeutic effects of CCM in patients with ischemic (ICM) compared to non-ischemic cardi...
BACKGROUND
This study evaluated the prognostic significance of cardiac magnetic resonance myocardial feature tracking (CMR-FT) in patients with Brugada syndrome (BrS) to detect subclinical alterations and predict major adverse events (MAE).
METHODS
CMR was performed in 106 patients with BrS and 25 healthy controls. Biventricular global strain anal...
Background
Cardiac radioablation is a novel treatment option for therapy-refractory ventricular tachycardia (VT) ineligible for catheter-ablation. Three-dimensional clinical target volume (CTV) definition is a key step and this complex interdisciplinary procedure includes VT-substrate identification based on electroanatomical mapping (EAM) and its...
Background
Only a minority of patients who receive an implantable cardioverter defibrillator (ICD) based on left ventricular ejection fraction (LVEF) receive appropriate ICD therapy. Peri-infarct scar zone assessed by late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) is possible substrate for ventricular tachyarrhytmias (VTA)....
Background
Single-session high-dose stereotactic radiotherapy (radiosurgery) is a new treatment option for otherwise untreatable patients suffering from refractory ventricular tachycardia (VT). In the initial single-center case studies and feasibility trials, cardiac radiosurgery has led to significant reductions of VT burden with limited toxicitie...
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 Patholog...
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 Patholog...
Background
Inherited arrhythmia syndromes and genetic cardiomyopathies attribute in a significant proportion to sudden cardiac death. Implantable cardioverter defibrillators (ICDs) are the cornerstone in the prevention of sudden death in high-risk patients. However, ICD therapy is also associated with high rates of inappropriate shocks and/or devic...
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...
Background:Thromboembolic complications such as ischemic stroke or peripheral arterial thromboembolism are known complications in hypertrophic cardiomyopathy (HCM). We sought to assess the clinical and cardiovascular magnetic resonance (CMR) characteristics of patients with HCM suffering from thromboembolic events and analyzed the predictors of the...
Aims:
Inappropriate shocks (IAS) remain a challenge for patients and physicians after implantation of the subcutaneous implantable cardioverter-defibrillator (S-ICD). The aims were to assess and characterize different patterns of IAS.
Methods and results:
Two hundred and thirty-nine patients were implanted with an S-ICD between 2010 and 2018 for...
Brugada syndrome (BrS) is a rare channelopathy associated with sudden cardiac death (SCD). Although outcome data of adult cohorts are well known, information on children are lacking. The aim of the present study was to analyze the clinical profile, treatment approach and long-term outcome of children affected with BrS. After a systematic review of...
Background and purpose:
Providing evidence for radiotherapy (RT)-induced effects on cardiac implantable electric devices (CIEDs) with focus on flattening filter free-volumetric modulated arc therapy (FFF-VMAT) at 6 and 10 MV as well as 3D-conformal radiotherapy (3D-CRT) at 18 MV.
Materials and methods:
68 CIEDs (64 implantable cardioverter-defib...
Background:
Brugada Syndrome is a genetic arrhythmogenic disease with a variable clinical spectrum. The role of clinical and ECG parameters in the risk stratification is still uncertain.
Aims:
In a large cohort of Brugada patients we analysed clinical and ECG features to determine the variables with prognostic value for the occurrence of a first...
Background
Short QT syndrome (SQTS) is associated with sudden cardiac death and implantable cardioverter-defibrillator (ICD) implantation is recommended in this rare disease. However, only a few SQTS families have been reported in literature with limited follow-up data.
Objectives
In the recent study, we describe the outcome data of 57 SQTS patien...
Background:
Defibrillation threshold (DFT) testing is commonly performed in patients undergoing subcutaneous defibrillator (S-ICD) implantation. There is a growing evidence that successful DFT testing correlates with implantation technique of the defibrillation lead and the pulse generator. However, in patients undergoing S-ICD pulse generator rep...
Aims:
Brugada syndrome (BrS) is associated with a pronounced risk to develop sudden cardiac death (SCD). Up to 21% of patients are related to mutations in SCN5A. Studies identified SCN10A as a contributor of BrS. However, the investigation of the human cellular phenotype of BrS in the presence of SCN10A mutations remains lacking. The objective of...
Purpose:
Dronedarone is a multichannel-blocking antiarrhythmic drug for the treatment of atrial fibrillation. Observational data hypothesized a cardioprotective effect. In an in vitro endothelial cell-platelet model, we evaluated the molecular atheroprotective effects of dronedarone.
Methods:
Following a 24-h incubation of human umbilical vein e...
Background
Short QT syndrome (SQTS) is a rare inheritable disease associated with sudden cardiac death. Data on long‐term outcomes of families with SQTS are limited.
Methods and Results
Seventeen patients with SQTS in 7 independent families (48% men; median age, 42.4 years; corrected QT interval, 324.9±40.8 ms) were followed up for 13.5±2.5 years....
Background:
Irreversible electroporation (IRE) is a novel tumor ablative therapy technique, using electric fields to induce apoptosis in target tissues. It is unclear whether these electric pulses of high field strength can cause cardiac damage and/or ablation induced arrhythmias.
Objective:
To systematically evaluate the safety of ECG gated IRE...
Figure S1 S‐ICD report of patient with one inappropriate shock: non‐sustained VT for 11 s, followed by a phase of T‐Wave oversensing for 15 s. T‐Wave oversensing leads to the inappropriate shock.
Background:
The wearable cardioverter-defibrillator (WCD) has emerged as a valuable tool to temporarily protect patients at risk for sudden cardiac death (SCD). The aim of this study was to determine the value of the WCD for therapy optimization of heart failure patients.
Methods:
One hundred five consecutive patients that received WCD between 4...
Hypertrophic cardiomyopathy (HCM) has a low risk for sudden cardiac death (SCD). The ESC clinical risk prediction model estimates the risk of SCD using clinical and echocardiographical parameters without taking into account cardiac magnetic resonance (CMR) parameters. Therefore, we compared the CMR characteristics of 149 patients with low, intermed...
Background
Cardiac contractility modulation (CCM) is an electrical‐device therapy for patients with heart failure with reduced ejection fraction (HFrEF). Patients with left ventricular ejection fraction (LVEF) ≤35% also have indication for an implantable cardioverter‐defibrillator (ICD), and in some cases subcutaneous ICD (S‐ICD) is selected.
Hypo...
Background
Up to 40% of patients with transvenous implantable cardioverter‐defibrillator (ICD) experience lead‐associated complications and may suffer from high complication rates when lead extraction is indicated. Subcutaneous ICD may represent a feasible alternative; however, the efficacy of the subcutaneous ICD in the detection and treatment of...
Sudden cardiac death (SCD) remains a major public health burden despite revolutionary progress in the last three decades in the treatment of ventricular tachyarrhythmia with the use of implantable cardioverter defibrillator (ICD) therapy. Survivors of sudden cardiac arrest are at high risk for recurrent tachyarrhythmia events. Early recognition of...
Sudden cardiac death and chronic heart failure are among the main contributors to persisting high mortality rates in Germany. In addition to removal of causal factors and guideline-conform pharmacological therapy, therapy with cardiac implantable electronic devices (CIED) is of undisputed importance. Subcutaneous defibrillators have the advantage t...
Aims Overlap syndromes of long QT 3 syndrome (LQT3) and the Brugada syndrome (BrS) have been reported. Identification of patients with an overlapping phenotype is crucial before initiation of Class I antiarrhythmic drugs for LQT3. Aim of the present study was to elucidate the yield of ajmaline challenge in unmasking the Brugada phenotype in patient...
Video S2. LAO projection of the reconstructed 3D heart model in a control, without overt ECG abnormalities is shown. Different voltage gradients between the epicardium and endocardium are color coded from +28.3 (red) to −28.3 mV (purple) and shown in slow motion, based on 1 heartbeat (depolarization and repolarization). During the terminal portion...
Video S3. LAO projection of the reconstructed 3D heart model in a patient with a typical RBBB is shown. Different voltage gradients between the epicardium and endocardium are color coded from +12 (red) to −12 mV (purple) and shown in slow motion, based on 1 heartbeat (depolarization and repolarization). During the terminal portion of the QRS, a pos...
Data S1. Supplemental methods.
Table S1. Demographic Data of Patients With Bundle Branch Block
Table S2. Demographic Data of Control Subjects
Table S3. Morphology of Local Unipolar EGs in Control Subjects
Table S4. Morphology of Local Unipolar EGs in BrS Patients With Type 1 ECG
Table S5. Comparison of Electrograms Obtained in the Right Ventri...
Video S1. LAO projection of the reconstructed 3D heart model in a patient with a spontaneous type 1 Brugada ECG is shown. Different voltage gradients between the epicardium and endocardium are color coded from +11.4 (red) to −11.4 mV (purple) and shown in slow motion, based on 1 heartbeat (depolarization and repolarization). During the terminal por...
Introduction
Fever can increase the susceptibility to supraventricular and ventricular arrhythmias, in which sodium channel dysfunction has been implicated. Whether fever influences the efficacy of sodium channel blocking drugs is unknown. The current study was designed to investigate the temperature dependent effects of distinct sodium channel blo...
Electrophysiological characterizations of hiPSC-CMs.
(A) Schematic diagram of an action potential (AP) trace recorded by patch-clamp in a hiPSC-CM, showing how AP parameters were analyzed. RP, resting potential; Vmax, maximal depolarization velocity; APA, amplitude of AP; APD50 and APD90, the AP duration at 50 and 90% repolarization. (B) Averaged v...
Effects of lidocaine and ranolazine on peak INa at the holding potential of -120 mV.
(A) Representaive traces of INa evoked by 100 ms pulses from -120 mV to -40 mV in absence (Ctr) and presence of 100 μM lidocaine at 36°C and 40°C. (B) Representaive traces of INa in absence (Ctr) and presence of 10 μM ranolazine at 36°C and 40°C. (C) Averaged value...
Action potential properties of hiPS-CMs paced at 1Hz.
(DOCX)
Use-dependent block of peak INa by lidocaine and ranolazine at 36°C and 40°C.
From holding potential of -80 mV, 40 pulses with the duration of 100 ms were applied to -30 mV at intervals of 300 ms. Peak INa evoked by every pulse (Ipn) was subtracted from that evoked by the first pulse (Ip1) normalized to Ip1 (Ip1-Ipn/Ifirst). The normalized values o...
TTX blocked INa and the effects of drugs on INa.
Shown are representaive INa traces recorded at -40 mV with the holding potential of -80 mV. 20 μM TTX inhibited both peak (A) and late (B) INa, and also prevented the effects of 30 μM flecainide (C), 100 μM lidocaine (D), 30 μM ajmaline (E) and 100 μM ranolazine on late INa.
(TIF)
Properties of INa-kinetics in iPS-CMs at 22°C, 36°C and 40°C.
(DOC)
Background. The underlying mechanisms of Brugada syndrome (BrS) are not completely understood. Recent studies provided evidence that the electrophysiological substrate, leading to electrocardiogram abnormalities and/or ventricular arrhythmias, is located in the right ventricular outflow tract (RVOT). The purpose of this study was to examine abnorma...
Introduction: Brugada syndrome (BrS) and Long QT 3 syndrome (LQT3) are caused by mutations in the SCN5A gene. The most common LQT3 causing mutation is SCN5A-E1784K, accounting for slightly over 10% of all genotyped unrelated LQT3 patients. Overlapping phenotypes of BrS, LQT3 and cardiac conduction disease have been reported for distinct mutations....
Objectives and Background: Atrial fibrillation (AF) is associated with clinical deterioration, stroke and disability in patients with hypertrophic cardiomyopathy (HCM). Therefore, the objective of this study was to evaluated cardiac magnetic resonance (CMR)-derived determinants for the occurrence of AF in patients with HCM.
Methods: 98 Patients wit...
Aims
The early repolarization pattern (ERP) has been shown to be associated with arrhythmias in patients with short QT syndrome, Brugada syndrome, and ischaemic heart disease. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome and related to malignant ventricular tachyarrhythmias in a structurally norma...
Aims
The purpose of the this study was to evaluate a possible genotype–phenotype correlation in BrS patients and to analyze possible associations with clinical events in affected patients. SCN5A gene encodes the alpha-subunit of the voltage-gated sodium channel NaV1.5. Its mutations are associated with a broad spectrum of hereditary arrhythmias suc...
Subcutaneous implantable cardioverter-defibrillator (S-ICD) is an implantable device for antiarrhythmic therapy with no intravascular leads.
We describe the technical feasibility of combining the S-ICD with other cardiac implantable electronic devices (CIEDs), including pacemakers with trans-venous or epicardial electrodes. We also provide the firs...
In the last few decades, defibrillator therapy has revolutionized treatment of patients at risk for sudden cardiac death. Multiple clinical trials have shown the benefit of implantable cardioverter-defibrillators (ICD) for primary and secondary prevention of sudden cardiac death. Being an entirely subcutaneous system, the S-ICD® avoids important pe...
Hypertrophic cardiomyopathy (HCM) causes various degrees of fibrosis resulting in left ventricular function impairment, which can be measured using mitral annular plane systolic excursion (MAPSE).
To determine the values for septal, lateral and average MAPSE using cardiovascular magnetic resonance (CMR) in healthy controls and patients with HCM; an...
This handout describes the simulation dataset KIT-20-PVC_Simulation-1906-10-30, which was contributed by the Karlsruhe Institute of Technology (KIT) to the Experimental Data and Geometric Analysis Repository (EDGAR) database.
To analyze long-term efficacy and survival in patients with chronic heart failure treated with cardiac contractility modulation.
81 patients implanted with a CCM device between 2004 and 2012 were included in this retrospective analysis. Changes in NYHA class, ejection fraction (EF), Minnesota Living with Heart Failure Questionnaire, NT-proBNP and p...
Aim
To compare cardiovascular magnetic resonance (CMR)-derived right ventricular fractional shortening (RVFS), tricuspid annular plane systolic excursion with a reference point within the right ventricular apex (TAPSEin) and with one outside the ventricle (TAPSEout) with the standard volumetric approach in patients with hypertrophic cardiomyopathy...
Background
Patients with a short QT syndrome (SQTS) have an increased risk for atrial, ventricular tachyarrhythmias and/or sudden cardiac death. PQ segment depression (PQD) is related to atrial fibrillation and carries a poor prognosis in the setting of acute inferior myocardial infarction and is a well defined ECG marker of acute pericarditis.
Ob...
