@article{WeidemannMaierStoerketal.2016, author = {Weidemann, Frank and Maier, Sebastian K. G. and St{\"o}rk, Stefan and Brunner, Thomas and Liu, Dan and Hu, Kai and Seydelmann, Nora and Schneider, Andreas and Becher, Jan and Canan-K{\"u}hl, Sima and Blaschke, Daniela and Bijnens, Bart and Ertl, Georg and Wanner, Christoph and Nordbeck, Peter}, title = {Usefulness of an implantable loop recorder to detect clinically relevant arrhythmias in patients with advanced fabry cardiomyopathy}, series = {The American Journal of Cardiology}, volume = {118}, journal = {The American Journal of Cardiology}, number = {2}, doi = {10.1016/j.amjcard.2016.04.033}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188093}, pages = {264-274}, year = {2016}, abstract = {Patients with genetic cardiomyopathy that involves myocardial hypertrophy often develop clinically relevant arrhythmias that increase the risk of sudden death. Consequently, guidelines for medical device therapy were established for hypertrophic cardiomyopathy, but not for conditions with only anecdotal evidence of arrhythmias, like Fabry cardiomyopathy. Patients with Fabry cardiomyopathy progressively develop myocardial fibrosis, and sudden cardiac death occurs regularly. Because 24-hour Holier electrocardiograms (ECGs) might not detect clinically important arrhythmias, we tested an implanted loop recorder for continuous heart rhythm surveillance and determined its impact on therapy. This prospective study included 16 patients (12 men) with advanced Fabry cardiomyopathy, relevant hypertrophy, and replacement fibrosis in "loco typico." No patients previously exhibited clinically relevant arrhythmias on Holier ECGs. Patients received an implantable loop recorder and were prospectively followed with telemedicine for a median of 1.2 years (range 0.3 to 2.0 years). The primary end point was a clinically meaningful event, which required a therapy change, captured with the loop recorder. Patients submitted data regularly (14 +/- 11 times per month). During follow-up, 21 events were detected (including 4 asystole, i.e., ECG pauses >= 3 seconds) and 7 bradycardia events; 5 episodes of intermittent atrial fibrillation (>3 minutes) and 5 episodes of ventricular tachycardia (3 sustained and 2 nonsustained). Subsequently, as defined in the primary end point, 15 events leaded to a change of therapy. These patients required therapy with a pacemaker or cardioverter defibrillator implantation and/or anticoagulation therapy for atrial fibrillation. In conclusion, clinically relevant arrhythmias that require further device and/or medical therapy are often missed with Holier ECGs in patients with advanced stage Fabry cardiomyopathy, but they can be detected by telemonitoring with an implantable loop recorder.}, language = {en} } @article{SeydelmannLiuKraemeretal.2016, author = {Seydelmann, Nora and Liu, Dan and Kr{\"a}mer, Johannes and Drechsler, Christiane and Hu, Kai and Nordbeck, Peter and Schneider, Andreas and St{\"o}rk, Stefan and Bijnens, Bart and Ertl, Georg and Wanner, Christoph and Weidemann, Frank}, title = {High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease}, series = {Journal of the American Heart Association}, volume = {5}, journal = {Journal of the American Heart Association}, number = {e002839}, doi = {10.1161/JAHA.115.002839}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165682}, year = {2016}, abstract = {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.}, language = {en} } @article{OderUeceylerLiuetal.2016, author = {Oder, Daniel and {\"U}ceyler, Nurcan and Liu, Dan and Hu, Kai and Petritsch, Bernhard and Sommer, Claudia and Ertl, Georg and Wanner, Christoph and Nordbeck, Peter}, title = {Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y}, series = {BMJ Open}, volume = {6}, journal = {BMJ Open}, doi = {10.1136/bmjopen-2015-010422}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161210}, pages = {e010422}, year = {2016}, abstract = {Objectives: The severity of Fabry disease is dependent on the type of mutation in the α-galactosidase A (AgalA) encoding gene (GLA). This study focused on the impact of the GLA haplotype D313Y on long-term organ involvement and function. Setting and participants: In this monocentric study, all participants presenting with the D313Y haplotype between 2001 and 2015 were comprehensively clinically investigated at baseline and during a 4-year follow-up if available. Five females and one male were included. Primary and secondary outcome measures: Cardiac, nephrological, neurological, laboratory and quality of life data. Results: AgalA enzyme activity in leucocytes (0.3±0.9 nmol/min/mg protein (mean±SD)) and serum lyso-Gb3 (0.6±0.3 ng/mL at baseline) were in normal range in all patients. Cardiac morphology and function were normal (left-ventricular (LV) ejection fraction 66±8\%; interventricular septum 7.7±1.4 mm; LV posterior wall 7.5±1.4 mm; normalised LV mass in MRI 52±9 g/m2; LV global longitudinal strain -21.6±1.9\%) and there were no signs of myocardial fibrosis in cardiac MRI. Cardiospecific biomarkers were also in normal range. Renal function was not impaired (estimated glomerular filtration rate MDRD 103±15 mL/min; serum-creatinine 0.75±0.07 mg/dL; cystatin-c 0.71±0.12 mg/L). One female patient (also carrying a Factor V Leiden mutation) had a transitory ischaemic attack. One patient showed white matter lesions in brain MRI, but none had Fabry-associated pain attacks, pain crises, evoked pain or permanent pain. Health-related quality of life analysis revealed a reduction in individual well-being. At long-term follow-up after 4 years, no significant change was seen in any parameter. Conclusions: The results of the current study suggest that the D313Y genotype does not lead to severe organ manifestations as seen in genotypes known to be causal for classical FD."}, language = {en} } @article{OderVerghoErtletal.2016, author = {Oder, Daniel and Vergho, Dorothee and Ertl, Georg and Wanner, Christoph and Nordbeck, Peter}, title = {Case report of a 45-year old female Fabry disease patient carrying two alpha-galactosidase A gene mutation alleles}, series = {BMC Medical Genetics}, volume = {17}, journal = {BMC Medical Genetics}, number = {46}, doi = {10.1186/s12881-016-0309-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146617}, year = {2016}, abstract = {Background X-chromosomal inheritance patterns and generally rare occurrence of Fabry disease (FD) account for mono-mutational hemizygous male and heterozygous female patients. Female mutation carriers are usually clinically much less severely affected, which has been explained by a suggested mosaicism in cell phenotype due to random allele shutdown. However, clinical evidence is scarce and potential additional effects in female gene carriers, which might account for specific clinical characteristics such as less severe chronic kidney disease, are yet unknown. Case presentation This article reports on a 45 year old female patient carrying the two alpha-galactosidase A gene mutations c.416A > G, p.N139S in exon 3 and c.708G > C, p.W236C in exon 5, but still showing only mild organ manifestations. Conclusion This current case highlights the importance of careful clinical characterization in patients with Fabry disease, who may show additional rare constellations and, therefore, are in need of personalized medicine. The impact of potential additional protective effects exceeding the presence of a non-pathogenic GLA allele in female gene carriers requires further investigation.}, language = {en} } @article{LiuHuNordbecketal.2016, author = {Liu, Dan and Hu, Kai and Nordbeck, Peter and Ertl, Georg and St{\"o}rk, Stefan and Weidemann, Frank}, title = {Longitudinal strain bull's eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy}, series = {European Journal of Medical Research}, volume = {21}, journal = {European Journal of Medical Research}, number = {21}, doi = {10.1186/s40001-016-0216-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146373}, year = {2016}, abstract = {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.}, language = {en} }