German Cardiovascular Research Center

München, Germany

German Cardiovascular Research Center

München, Germany
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Conti S.,Southlake Regional Health Center | Reiffel J.A.,Columbia University | Gersh B.J.,Mayo Medical School | Kowey P.R.,Lankenau Institute for Medical Research | And 6 more authors.
Journal of Atrial Fibrillation | Year: 2017

Given the high prevalence and risk of stroke associated with atrial fibrillation (AF), detection strategies have important public health implications. The ongoing prospective, single-arm, open-label, multicenter REVEAL AF trial is evaluating the incidence of previously undetected AF using an insertable cardiac monitor (ICM) in patients without prior AF or device implantation, but who could be at risk for AF due to their demographic characteristics, +/-non-specific but compatible symptoms. Enrollment required an elevated AF risk profile defined as CHADS2≥3 or CHADS2=2 plus one or more of the following: coronary artery disease, renal impairment, sleep apnea or chronic obstructive pulmonary disease. Exclusions included stroke or transient ischemic attack occurring in the previous year. Of 450 subjects screened, 399 underwent a device insertion attempt, and 395 were included in the final analysis (Reveal XT: n=122; Reveal LINQ: n=273; excluded: n=4). Participants were primarily identified by demographic characteristics and the presence of nonspecific symptoms, but without prior documentation of "overt" AF. The most common symptoms were palpitations (51%), dizziness/lightheadedness/pre-syncope (36%), and shortness of breath (36%). Over 100 subjects were enrolled in each pre-defined CHADS2 subgroup (2, 3 and.4). AF risk factors not included in the CHADS2 score were well represented (prevalence.15%). Procedure and/or device related serious adverse events were low, with the miniaturized Reveal LINQ ICM having a more favorable safety profile than the predicate Reveal XT (all: n=13 [3.3%]; LINQ: n=6 [2.2%]; XT: n=7 [5.7%]). These data demonstrate that REVEAL AF was successful in enrolling its target population, high risk patients were willing to undergo ICM monitoring for AF screening, and ICM use in this group is becoming increasingly safe with advancements in technology. A clinically meaningful incidence of device detected AF in this study will inform clinical decisions regarding ICM use for AF screening in patients at risk.

Jenewein T.,Goethe University Frankfurt | Beckmann B.M.,Ludwig Maximilians University of Munich | Beckmann B.M.,German Cardiovascular Research Center | Rose S.,Goethe University Frankfurt | And 10 more authors.
Forensic Science International | Year: 2017

Mutations in the cardiac sodium channel gene SCN5A may result in various arrhythmia syndromes such as long QT syndrome type 3 (LQTS), Brugada syndrome (BrS), sick sinus syndrome (SSS), cardiac conduction diseases (CCD) and possibly dilated cardiomyopathy (DCM). In most of these inherited cardiac arrhythmia syndromes the phenotypical expression may range from asymptomatic phenotypes to sudden cardiac death (SCD). A 16-year-old female died during sleep. Autopsy did not reveal any explanation for her death and a genetic analysis was performed. A variant in the SCN5A gene (E1053K) that was previously described as disease causing was detected. Family members are carriers of the same E1053K variant, some even in a homozygous state, but surprisingly did not exhibit any pathological cardiac phenotype. Due to the lack of genotype-phenotype correlation further genetic studies were performed. A novel deletion in the promoter region of SCN5A was identified in the sudden death victim but was absent in other family members. These findings demonstrate the difficulties in interpreting the results of a family-based genetic screening and underline the phenotypic variability of SCN5A mutations. © 2017 Elsevier B.V.

Sohns J.M.,University of Gottingen | Sohns J.M.,German Cardiovascular Research Center | Staab W.,University of Gottingen | Staab W.,German Cardiovascular Research Center | And 14 more authors.
Journal of Magnetic Resonance Imaging | Year: 2014

Purpose: To investigate the presence of relevant vascular and incidental extravascular findings in patients undergoing magnetic resonance angiography (MRA) of the thoracic aorta and origin of the great vessels. Materials and Methods: In all, 165 consecutive patients (mean age 61612 years) underwent 1.5 T MRA of the thorax. Two researchers identified vascular and incidental extravascular findings. Clinically relevant vascular findings were defined. Extravascular findings were categorized as minor (Group A, without change in patient treatment), intermediate (Group B, unclear clinical relevance, requiring additional investigations), and major (Group C, causing a change in patient treatment). Results: A total of 306 relevant vascular findings were found in our cohort. A total of 397 extravascular findings were observed among the patients and were classified as Group A findings in 81.9% (325/397 findings, observed in 146 of 165 patients), as Group B findings in 15.4% (61/397 findings, observed in 52 of 165 patients), and as Group C in 2.8% of findings (11/397). The clinically relevant Group C findings were observed in 6.7% of patients (11/165), comprising eight previously unknown neoplasms (4.8% of 165), two patients with hemodynamically relevant pericardial effusion (1.2% of 165), and one patient with spondylodiscitis (0.6% of 165) detected by MRA. Conclusion: Relevant vascular and extravascular findings were found in patients referred for thoracic MRA. Most extravascular findings can be categorized by MRA as minor, while others required further diagnostics since they may be malignant or otherwise clinically relevant.. © 2013 Wiley Periodicals, Inc.

Rosenkranz S.,University of Cologne | Gibbs J.S.R.,Imperial College London | Gibbs J.S.R.,Hammersmith Hospital London | Wachter R.,University of Gottingen | And 4 more authors.
European Heart Journal | Year: 2016

In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequent and have important impact on disease progression, morbidity, and mortality, and therefore warrant clinical attention. Pulmonary hypertension related to left heart disease (LHD) by far represents the most common form of PH, accounting for 65-80% of cases. The proper distinction between pulmonary arterial hypertension and PH-LHD may be challenging, yet it has direct therapeutic consequences. Despite recent advances in the pathophysiological understanding and clinical assessment, and adjustments in the haemodynamic definitions and classification of PH-LHD, the haemodynamic interrelations in combined post- and pre-capillary PH are complex, definitions and prognostic significance of haemodynamic variables characterizing the degree of pre-capillary PH in LHD remain suboptimal, and there are currently no evidence-based recommendations for the management of PH-LHD. Here, we highlight the prevalence and significance of PH and RV dysfunction in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), and provide insights into the complex pathophysiology of cardiopulmonary interaction in LHD, which may lead to the evolution from a 'left ventricular phenotype' to a 'right ventricular phenotype' across the natural history of HF. Furthermore, we propose to better define the individual phenotype of PH by integrating the clinical context, non-invasive assessment, and invasive haemodynamic variables in a structured diagnostic work-up. Finally, we challenge current definitions and diagnostic short falls, and discuss gaps in evidence, therapeutic options and the necessity for future developments in this context. © 2015 The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Zhang L.,Ludwig Maximilians University of Munich | Zhang L.,TU Munich | Orban M.,Ludwig Maximilians University of Munich | Orban M.,TU Munich | And 33 more authors.
Journal of Experimental Medicine | Year: 2012

Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P-S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia. © 2012 Zhang et al.

Mayer F.,University of Duisburg - Essen | Stahrenberg R.,University of Gottingen | Groschel K.,University of Gottingen | Groschel K.,University of Mainz | And 12 more authors.
Clinical Research in Cardiology | Year: 2013

Background and purpose: Prolonged Holter monitoring of patients with cerebral ischemia increases the detection rate of paroxysmal atrial fibrillation (PAF); this leads to improved antithrombotic regimens aimed at preventing recurrent ischemic strokes. The aim of this study was to compare a 7-day-Holter monitoring (7-d-Holter) alone or in combination with prior selection via transthoracic echocardiography (TTE) to a standard 24-h-Holter using a cost-utility analysis. Methods: Lifetime cost, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were estimated for a cohort of patients with acute cerebral ischemia and no contraindication to oral anticoagulation. A Markov model was developed to simulate the long-term course and progression of cerebral ischemia considering the different diagnostic algorithms (24-h-Holter, 7-d-Holter, 7-d-Holter after preselection by TTE). Clinical data for these algorithms were derived from the prospective observational Find-AF study (ISRCTN 46104198). Results: Predicted lifelong discounted costs were 33,837 € for patients diagnosed by the 7-d-Holter and 33,852 € by the standard 24-h-Holter. Cumulated QALYs were 3.868 for the 7-d-Holter compared to 3.844 for the 24-h-Holter. The 7-d-Holter dominated the 24-h-Holter in the base-case scenario and remained cost-effective in extensive sensitivity analysis of key input parameter with a maximum of 8,354 €/QALY gained. Preselecting patients for the 7-d-Holter had no positive effect on the cost-effectiveness. Conclusions: A 7-d-Holter to detect PAF in patients with cerebral ischemia is cost-effective. It increases the detection which leads to improved antithrombotic regimens; therefore, it avoids recurrent strokes, saves future costs, and decreases quality of life impairment. Preselecting patients by TTE does not improve cost-effectiveness. © 2013 The Author(s).

Sohns J.M.,University of Gottingen | Sohns J.M.,German Cardiovascular Research Center | Staab W.,University of Gottingen | Dabir D.,University of Bonn | And 4 more authors.
Clinical Imaging | Year: 2014

Purpose: Aim of this study was to investigate the incidence of relevant biliary and extrabiliary findings in patients undergoing magnetic resonance cholangiopancreatography (MRCP). Materials and Methods: Three hundred eighty-four patients underwent 1.5-Tesla MRCP, and relevant biliary and extra-biliary findings were identified. Results: Four hundred twenty-two biliary findings were identified in 384 patients (75%; 1.1 per patient). Ninety-five patients were free of any relevant biliary finding (25%). Incidental extrabiliary findings were observed in 763 patients (1.98/patient). Conclusion: Most of the findings can be diagnosed by MRCP, while others require further examination. Interdisciplinary involvement is recommended to optimize clinical categorization, management, and treatment of these incidental findings. © 2014 Elsevier Inc.

Hellenkamp K.,University of Gottingen | Schwung J.,University of Gottingen | Rossmann H.,Johannes Gutenberg University Mainz | Kaeberich A.,Johannes Gutenberg University Mainz | And 7 more authors.
European Respiratory Journal | Year: 2015

The prognostic value of copeptin, the C-terminal fragment of the precursor protein of vasopressin which is released upon stress, and hypotension in pulmonary embolism is unknown, especially if combined with biomarkers reflecting different pathophysiological axes such as myocardial injury (highsensitivity troponin T (hsTnT)) and stretch (N-terminal pro-brain natriuretic peptide (NT-proBNP)). We prospectively studied 268 normotensive pulmonary embolism patients included in a single-centre cohort study. Patients with an adverse 30-day outcome (5.6%) had higher copeptin levels than patients with a favourable course (median (interquartile range) 51.8 (21.6-90.8) versus 13.2 (5.9-39.3) pmol·L-1; p=0.020). Patients with copeptin levels above the calculated optimal cut-off value of 24 pmol·L-1 had a 5.4-fold increased risk for an adverse outcome (95% CI 1.68-17.58; p=0.005). We developed a strategy for risk stratification based on biomarkers. None of 141 patients (52.6%) with hsTnT <14 pg·mL-1 or NT-proBNP <600 pg·mL-1 had an adverse outcome (low risk). Copeptin ≥24 pmol·L-1 stratified patients with elevated hsTnT and NT-proBNP as intermediate-low and intermediate-high risk (5.6% and 20.0% adverse outcome, respectively). Compared to the algorithm proposed by the 2014 European Society of Cardiology guideline, more patients were classified as low risk (52.8% versus 17.5%, p<0.001) and more patients in the intermediate-high risk group had an adverse outcome (20.0% versus 11.6%). Copeptin might be helpful for risk stratification of normotensive patients with pulmonary embolism, especially if integrated into a biomarker-based algorithm. Copyright © ERS 2015.

Wakili R.,Ludwig Maximilians University of Munich | Wakili R.,German Cardiovascular Research Center | Siebermair J.,Ludwig Maximilians University of Munich | Fichtner S.,Ludwig Maximilians University of Munich | And 11 more authors.
Europace | Year: 2016

Aims Pulmonary vein isolation (PVI) is an established therapy for atrial fibrillation (AF). However, PVI remains a time-consuming procedure. A novel multipolar irrigated radiofrequency (RF) ablation catheter (nMARQ™) is aiming to improve PVI. We investigated the influence on procedural parameters and assessed clinical outcomes after PVI using this novel catheter. Methods and results Fifty-eight consecutive patients with paroxysmal AF were equally allocated (n = 29/group) to PVI treatment with (i) the novel multipolar ablation catheter (nMARQ™) and (ii) a standard single-tip ablation catheter (SAC). Study endpoints included procedure time, fluoroscopy time, radiation dose, RF time, number of energy applications, and clinical outcome defined as freedom from AF after a single procedure. Successful PVI was confirmed by a separate circular, multipolar mapping catheter in all patients treated with the nMARQ™. Pulmonary vein isolation was achieved in 100% in the SAC group. In the nMARQ™ group, PVI was suggested in all patients. However, confirmatory mapping revealed persistent pulmonary vein (PV) conduction in 19 out of 29 nMARQ™ patients. These patients underwent further ablation, which still failed to achieve PVI in 5 of the 29 nMARQ™ patients, mainly due to significant temperature rise in the oesophagus and device-related limitations reaching the right inferior PV. Mean fluoroscopy time (31 ± 12 vs. 23 ± 10 min, P < 0.05) and (132 ± 37 vs. 109 ± 30 min, P < 0.05) were longer in nMARQ™ vs. SAC patients. Radiofrequency time was shorter in nMARQ™ vs. SAC group (21 ± 9 vs. 35 ± 12 min, P < 0.001). Radiation dose and the number of energy applications did not differ between both groups. Clinical outcome analysis revealed no significant differences (nMARQ™: 72 vs. SAC: 72%) after a mean follow-up of 373 ± 278 days. Conclusion The use of the nMARQ™ catheter is associated with important device-related limitations to achieve successful PVI. However, clinical outcomes were equivalent in nMARQ™- and SAC-treated patients. © 2016 Published on behalf of the European Society of Cardiology. All rights reserved.

Frahm J.,Biomedizinische Nmr Forschungs Gmbh Am Max Planck Institute For Biophysikalische Chemie | Frahm J.,German Cardiovascular Research Center | Schatz S.,Biomedizinische Nmr Forschungs Gmbh Am Max Planck Institute For Biophysikalische Chemie | Untenberger M.,Biomedizinische Nmr Forschungs Gmbh Am Max Planck Institute For Biophysikalische Chemie | And 9 more authors.
Open Medical Imaging Journal | Year: 2014

Purpose: To evaluate the temporal accuracy of a self-consistent nonlinear inverse reconstruction method (NLINV) for real-time MRI using highly undersampled radial gradient-echo sequences and to present an open source framework for the motion assessment of real-time MRI methods. Methods: Serial image reconstructions by NLINV combine a joint estimation of individual frames and corresponding coil sensitivities with temporal regularization to a preceding frame. The temporal fidelity of the method was determined with a phantom consisting of water-filled tubes rotating at defined angular velocity. The conditions tested correspond to real-time cardiac MRI using SSFP contrast at 1.5 T (40 ms resolution) and T1 contrast at 3.0 T (33 ms and 18 ms resolution). In addition, the performance of a post-processing temporal median filter was evaluated. Results: NLINV reconstructions without temporal filtering yield accurate estimations as long as the speed of a small moving object corresponds to a spatial displacement during the acquisition of a single frame which is smaller than the object itself. Faster movements may lead to geometric distortions. For small objects moving at high velocity, a median filter may severely compromise the spatiotemporal accuracy. Conclusion: NLINV reconstructions offer excellent temporal fidelity as long as the image acquisition time is short enough to adequately sample ("freeze") the object movement. Temporal filtering should be applied with caution. The motion framework emerges as a valuable tool for the evaluation of real-time MRI methods. © Frahm et al.

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