TY - JOUR A1 - Wagner, Martin A1 - Krämer, Johannes A1 - Blohm, Elisabeth A1 - Vergho, Dorothee A1 - Weidemann, Frank A1 - Breunig, Frank A1 - Wanner, Christoph T1 - Kidney function as an underestimated factor for reduced health related quality of life in patients with Fabry disease N2 - Background: Impairments of health related quality of life (HRQoL) are frequently observed in Fabry disease (FD) and are known to be related to neuropathic pain and cardiovascular events. This study aimed to explore the role of chronic kidney disease (CKD) in a large cohort of patients with FD. Methods: In 96 patients (53% female; age 40 ± 12 yrs) with genetically proven FD, HRQoL was assessed by the Medical Outcomes Study (SF-36) questionnaire. All patients were naïve to enzyme replacement therapy. Three categories for kidney dysfunction were chosen, eGFR ≥/<60 ml/min/1.73 m2 or need of renal replacement therapy (RRT). Minor (e.g. arrhythmia, angina pectoris, etc.) and major (e.g. myocardial infarction, coronary artery bypass, stroke or implantable cardioverter-defibrillator) vascular events as well as pain and pain therapy were considered in linear regression analyses with the dimensions of HRQoL. Results: Ten patients (10%) had impaired kidney function and a further nine were on RRT (9.4%). Kidney function and pain emerged as the main factors associated with lower scores on the SF 36, in particular on physical components (PCS beta-coefficients for CKD −6.2, for RRT −11.8, for pain −9.1, p < 0.05, respectively), while controlling for gender, vascular event and pain-therapy. Relationships were found for mental aspects of HRQoL. Age and history of vascular events were not related to HRQoL. Conclusion: Cardiovascular events and pain are important factors related to HRQoL, social functioning and depression. Our study highlights impaired chronic kidney disease, in particular after initiation of RRT, as a strong determinant of reduced HRQoL in FD. KW - Quality of life KW - SF-36 KW - Chronic kidney disease KW - Fabry disease Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111159 UR - http://www.biomedcentral.com/1471-2369/15/188 ER - TY - JOUR A1 - Seydelmann, Nora A1 - Liu, Dan A1 - Krämer, Johannes A1 - Drechsler, Christiane A1 - Hu, Kai A1 - Nordbeck, Peter A1 - Schneider, Andreas A1 - Störk, Stefan A1 - Bijnens, Bart A1 - Ertl, Georg A1 - Wanner, Christoph A1 - Weidemann, Frank T1 - High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease JF - Journal of the American Heart Association N2 - Background High‐sensitivity troponin (hs‐TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs‐TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow‐up study to assess longitudinal hs‐TNT changes relative to fibrosis and cardiomyopathy progression. Methods and Results For the prospective analysis, hs‐TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry‐associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs‐TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs‐TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95% CI, 3.56–302.59]; P=0.002); patients with elevated baseline hs‐TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1–3.3] %; follow‐up, 3.2 [2.3–4.9] %; P<0.001) and slightly elevated hs‐TNT (baseline, 44.7 [30.1–65.3] ng/L; follow‐up, 49.1 [27.6–69.5] ng/L; P=0.116) during follow‐up. Left ventricular wall thickness and EF of patients with elevated hs‐TNT were decreased during follow‐up, indicating potential cardiomyopathy progression. Conclusions hs‐TNT is an accurate, easily accessible clinical blood biomarker for detecting replacement fibrosis in patients with Fabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs‐TNT could be helpful for staging and follow‐up of Fabry patients. KW - biomarker KW - cardiomyopathy KW - fabry disease KW - myocardial fibrosis KW - troponin T Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165682 VL - 5 IS - e002839 ER - TY - JOUR A1 - Liu, Dan A1 - Hu, Kai A1 - Nordbeck, Peter A1 - Ertl, Georg A1 - Störk, Stefan A1 - Weidemann, Frank T1 - Longitudinal strain bull's eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy JF - European Journal of Medical Research N2 - Despite substantial advances in the imaging techniques and pathophysiological understanding over the last decades, identification of the underlying causes of left ventricular hypertrophy by means of echocardiographic examination remains a challenge in current clinical practice. The longitudinal strain bull’s eye plot derived from 2D speckle tracking imaging offers an intuitive visual overview of the global and regional left ventricular myocardial function in a single diagram. The bull’s eye mapping is clinically feasible and the plot patterns could provide clues to the etiology of cardiomyopathies. The present review summarizes the longitudinal strain, bull’s eye plot features in patients with various cardiomyopathies and concentric left ventricular hypertrophy and the bull’s eye plot features might serve as one of the cardiac workup steps on evaluating patients with left ventricular hypertrophy. KW - speckle tracking imaging KW - bull’s eye plot KW - cardiomyopathy KW - left ventricular hypertrophy Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146373 VL - 21 IS - 21 ER - TY - JOUR A1 - Üçeyler, Nurcan A1 - Homola, György A. A1 - González, Hans Guerrero A1 - Kramer, Daniela A1 - Wanner, Christoph A1 - Weidemann, Frank A1 - Solymosi, László A1 - Sommer, Claudia T1 - Increased Arterial Diameters in the Posterior Cerebral Circulation in Men with Fabry Disease N2 - A high load of white matter lesions and enlarged basilar arteries have been shown in selected patients with Fabry disease, a disorder associated with an increased stroke risk. We studied a large cohort of patients with Fabry disease to differentially investigate white matter lesion load and cerebral artery diameters. We retrospectively analyzed cranial magnetic resonance imaging scans of 87 consecutive Fabry patients, 20 patients with ischemic stroke, and 36 controls. We determined the white matter lesion load applying the Fazekas score on fluid-attenuated inversion recovery sequences and measured the diameters of cerebral arteries on 3D-reconstructions of the time-of-flight-MR-angiography scans. Data of different Fabry patient subgroups (males – females; normal – impaired renal function) were compared with data of patients with stroke and controls. A history of stroke or transient ischemic attacks was present in 4/30 males (13%) and 5/57 (9%) females with Fabry disease, all in the anterior circulation. Only one man with Fabry disease showed confluent cerebral white matter lesions in the Fazekas score assessment (1%). Male Fabry patients had a larger basilar artery (p<0.01) and posterior cerebral artery diameter (p<0.05) compared to male controls. This was independent of disease severity as measured by renal function and did not lead to changes in arterial blood flow properties. A basilar artery diameter of >3.2 mm distinguished between men with Fabry disease and controls (sensitivity: 87%, specificity: 86%, p<0.001), but not from stroke patients. Enlarged arterial diameters of the posterior circulation are present only in men with Fabry disease independent of disease severity. KW - Arterial Diameters KW - ischemic stroke KW - magnetic resonance imaging KW - stroke KW - cerebral arteries KW - renal system KW - central nervous system KW - blood flow KW - lesions Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112614 ER - TY - JOUR A1 - Gassenmaier, Tobias A1 - Petritsch, Bernhard A1 - Kunz, Andreas S. A1 - Gkaniatsas, Spyridon A1 - Gaudron, Philipp D. A1 - Weidemann, Frank A1 - Nordbeck, Peter A1 - Beer, Meinrad T1 - Long term evolution of MRI characteristics in a case of atypical left lateral wall hypertrophic cardiomyopathy JF - World Journal of Cardiology N2 - We are reporting a long-time magnetic resonance imaging (MRI) follow-up in a rare case of cardiac left lateral wall hypertrophy. Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder and a significant cause of sudden cardiac death. Cardiac magnetic resonance (CMR) imaging can be a valuable tool for assessment of detailed information on size, localization, and tissue characteristics of hypertrophied myocardium. However, there is still little knowledge of long-term evolution of HCM as visualized by magnetic resonance imaging. Recently, our group reported a case of left lateral wall HCM as a rare variant of the more common forms, such as septal HCM, or apical HCM. As we now retrieved an old cardiac MRI acquired in this patient more than 20 years ago, we are able to provide the thrilling experience of an ultra-long MRI follow-up presentation in this rare case of left lateral wall hypertrophy. Furthermore, this case outlines the tremendous improvements in imaging quality within the last two decades of CMR imaging. KW - cardiac magnetic resonance imaging KW - hypertrophic cardiomyopathy KW - follow-up KW - atypical KW - left lateral wall Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124934 VL - 7 IS - 6 ER - TY - JOUR A1 - Weidemann, Frank A1 - Sanchez-Nino, Maria D. A1 - Politei, Juan A1 - Oliveira, João-Paulo A1 - Wanner, Christoph A1 - Warnock, David G. A1 - Oritz, Alberto T1 - Fibrosis: a key feature of Fabry disease with potential therapeutic implications JF - Orphanet Journal of Rare Diseases N2 - Fabry disease is a rare X-linked hereditary disease caused by mutations in the AGAL gene encoding the lysosomal enzyme alpha-galactosidase A. Enzyme replacement therapy (ERT) is the current cornerstone of Fabry disease management. Involvement of kidney, heart and the central nervous system shortens life span, and fibrosis of these organs is a hallmark of the disease. Fibrosis was initially thought to result from tissue ischemia secondary to endothelial accumulation of glycosphingolipids in the microvasculature. However, despite ready clearance of endothelial deposits, ERT is less effective in patients who have already developed fibrosis. Several potential explanations of this clinical observation may impact on the future management of Fabry disease. Alternative molecular pathways linking glycosphingolipids and fibrosis may be operative; tissue injury may recruit secondary molecular mediators of fibrosis that are unresponsive to ERT, or fibrosis may represent irreversible tissue injury that limits the therapeutic response to ERT. We provide an overview of Fabry disease, with a focus on the assessment of fibrosis, the clinical consequences of fibrosis, and recent advances in understanding the cellular and molecular mechanisms of fibrosis that may suggest novel therapeutic approaches to Fabry disease. KW - Fabry KW - fibrosis KW - podocyte KW - Lyso-Gb3 KW - kidney KW - enzyme replacement therapy KW - alpha-galactosidase-A KW - focal semental glomerulosclerosis KW - cardiovascular magnetic-resonance KW - left-ventricular hypertrophy KW - biopsy findings KW - agalsidase-beta KW - natural-history data KW - cardiac energy metabolism KW - randomized controlled trial Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124773 SN - 1750-1172 VL - 8 IS - 116 ER - TY - JOUR A1 - Liu, Dan A1 - Hu, Kai A1 - Pelzer, Heinz-Theo A1 - Störk, Stefan A1 - Weidemann, Frank T1 - Journey of a patient with chronic thromboembolic pulmonary hypertension JF - European Journal of Medical Research N2 - Right ventricle (RV) dysfunction is a key outcome determinant and a leading cause of death for patients with chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we followed the 5-year clinical journey of a patient with CTEPH. The tricuspid pressure gradient was significantly increased in the early phase of CTEPH and “normalized” at the late phase of this patient’s clinical journey, but this “normalized” gradient is not a positive treatment response but rather an ominous sign of advancing right heart failure owing to an exhaustion of RV contractile function. Thus, appropriate interpretation of the tricuspid pressure gradient change is of importance for assessing RV dysfunction and treatment outcome during follow-up in patients with CTEPH. Besides systolic pulmonary artery pressure (SPAP), other RV functional parameters such as tricuspid annular plane systolic excursion, RV fractional area change, and RV longitudinal strain, together with clinical markers, may provide additional guidance regarding functional improvement or progression in patients with CTEPH. KW - tricuspid pressure gradient KW - chronic thromboembolic pulmonary hypertension Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125009 VL - 20 IS - 20 ER - TY - JOUR A1 - Liu, Dan A1 - Hu, Kai A1 - Niemann, Markus A1 - Herrmann, Sebastian A1 - Cikes, Maja A1 - Störk, Stefan A1 - Beer, Meinrad A1 - Gaudron, Philipp Daniel A1 - Morbach, Caroline A1 - Knop, Stefan A1 - Geissinger, Eva A1 - Ertl, Georg A1 - Bijnens, Bart A1 - Weidemann, Frank T1 - Impact of Regional Left Ventricular Function on Outcome for Patients with AL Amyloidosis JF - PLoS ONE N2 - Objectives The aim of this study was to explore the left ventricular (LV) deformation changes and the potential impact of deformation on outcome in patients with proven light-chain (AL) amyloidosis and LV hypertrophy. Background Cardiac involvement in AL amyloidosis patients is associated with poor outcome. Detecting regional cardiac function by advanced non-invasive techniques might be favorable for predicting outcome. Methods LV longitudinal, circumferential and radial peak systolic strains (Ssys) were assessed by speckle tracking imaging (STI) in 44 biopsy-proven systemic AL amyloidosis patients with LV hypertrophy (CA) and in 30 normal controls. Patients were divided into compensated (n = 18) and decompensated (n = 26) group based on clinical assessment and followed-up for a median period of 345 days. Results Ejection fraction (EF) was preserved while longitudinal Ssys (LSsys) was significantly reduced in both compensated and decompensated groups. Survival was significantly reduced in decompensated group (35% vs. compensated 78%, P = 0.001). LSsys were similar in apical segments and significantly reduced in basal segments between two patient groups. LSsys at mid-segments were significantly reduced in all LV walls of decompensated group. Patients were further divided into 4 subgroups according to the presence or absence of reduced LSsys in no (normal), only basal (mild), basal and mid (intermediate) and all segments of the septum (severe). This staging revealed continuously worse prognosis in proportion to increasing number of segments with reduced LSsys (mortality: normal 14%, mild 27%, intermediate 67%, and severe 64%). Mid-septum LSsys<11% suggested a 4.8-fold mortality risk than mid-septum LSsys≥11%. Multivariate regression analysis showed NYHA class and mid-septum LSsys were independent predictors for survival. Conclusions Reduced deformation at mid-septum is associated with worse prognosis in systemic amyloidosis patients with LV hypertrophy. KW - regression analysis KW - ejection fraction KW - echocardiography KW - cardiac transplantation KW - deformation KW - amyloidosis KW - prognosis KW - stem cell transplantation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130293 VL - 8 IS - 3 ER - TY - JOUR A1 - Liu, Dan A1 - Hu, Kai A1 - Störk, Stefan A1 - Herrmann, Sebastian A1 - Kramer, Bastian A1 - Cikes, Maja A1 - Gaudron, Philipp Daniel A1 - Knop, Stefan A1 - Ertl, Georg A1 - Bijnens, Bart A1 - Weidemann, Frank T1 - Predictive Value of Assessing Diastolic Strain Rate on Survival in Cardiac Amyloidosis Patients with Preserved Ejection Fraction JF - PLOS ONE N2 - Objectives: Since diastolic abnormalities are typical findings of cardiac amyloidosis (CA), we hypothesized that speckle-tracking-imaging (STI) derived longitudinal early diastolic strain rate (LSRdias) could predict outcome in CA patients with preserved left ventricular ejection fraction (LVEF >50%). Background: Diastolic abnormalities including altered early filling are typical findings and are related to outcome in CA patients. Reduced longitudinal systolic strain (LSsys) assessed by STI predicts increased mortality in CA patients. It remains unknown if LSRdias also related to outcome in these patients. Methods: Conventional echocardiography and STI were performed in 41 CA patients with preserved LVEF (25 male; mean age 65±9 years). Global and segmental LSsys and LSRdias were obtained in six LV segments from apical 4-chamber views. Results: Nineteen (46%) out of 41 CA patients died during a median of 16 months (quartiles 5–35 months) follow-up. Baseline mitral annular plane systolic excursion (MAPSE, 6±2 vs. 8±3 mm), global LSRdias and basal-septal LSRdias were significantly lower in non-survivors than in survivors (all p<0.05). NYHA class, number of non-cardiac organs involved, MAPSE, mid-septal LSsys, global LSRdias, basal-septal LSRdias and E/LSRdias were the univariable predictors of all-cause death. Multivariable analysis showed that number of non-cardiac organs involved (hazard ratio [HR] = 1.96, 95% confidence interval [CI] 1.17–3.26, P = 0.010), global LSRdias (HR = 7.30, 95% CI 2.08–25.65, P = 0.002), and E/LSRdias (HR = 2.98, 95% CI 1.54–5.79, P = 0.001) remained independently predictive of increased mortality risk. The prognostic performance of global LSRdias was optimal at a cutoff value of 0.85 S−1 (sensitivity 68%, specificity 67%). Global LSRdias <0.85 S−1 predicted a 4-fold increased mortality in CA patients with preserved LVEF. Conclusions: STI-derived early diastolic strain rate is a powerful independent predictor of survival in CA patients with preserved LVEF. KW - diagnostic medicine KW - echocardiography KW - prognosis KW - calcium imaging KW - ejection fraction KW - death rates KW - amyloidosis KW - deformation Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-118024 SN - 1932-6203 VL - 9 IS - 12 ER - TY - JOUR A1 - Üçeyler, Nurcan A1 - Kahn, Ann-Kathrin A1 - Kramer, Daniela A1 - Zeller, Daniel A1 - Casanova-Molla, Jordi A1 - Wanner, Christoph A1 - Weidemann, Frank A1 - Katsarava, Zaza A1 - Sommer, Claudia T1 - Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case–control study JF - BMC Neurology N2 - Background Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP). Methods In this case–control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function. Results All Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients. Conclusion Small fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction. KW - Fabry disease KW - Pain-related evoked potentials KW - Small fiber neuropathy KW - A-delta fibers Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96527 UR - http://www.biomedcentral.com/1471-2377/13/47 ER -