@article{ChenLiuWeidemannetal.2021, author = {Chen, Menjia and Liu, Dan and Weidemann, Frank and Lengenfelder, Bj{\"o}rn Daniel and Ertl, Georg and Hu, Kai and Frantz, Stefan and Nordbeck, Peter}, title = {Echocardiographic risk factors of left ventricular thrombus in patients with acute anterior myocardial infarction}, series = {ESC Heart Failure}, volume = {8}, journal = {ESC Heart Failure}, number = {6}, doi = {10.1002/ehf2.13605}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261067}, pages = {5248-5258}, year = {2021}, abstract = {Aims This study aimed to identify echocardiographic determinants of left ventricular thrombus (LVT) formation after acute anterior myocardial infarction (MI). Methods and results This case-control study comprised 55 acute anterior MI patients with LVT as cases and 55 acute anterior MI patients without LVT as controls, who were selected from a cohort of consecutive patients with ischemic heart failure in our hospital. The cases and controls were matched for age, sex, and left ventricular ejection fraction. LVT was detected by routine/contrast echocardiography or cardiac magnetic resonance imaging during the first 3 months following MI. Formation of apical aneurysm after MI was independently associated with LVT formation [72.0\% vs. 43.5\%, odds ratio (OR) = 5.06, 95\% confidence interval (CI) 1.65-15.48, P = 0.005]. Echocardiographic risk factors associated with LVT formation included reduced mitral annular plane systolic excursion (<7 mm, OR = 4.69, 95\% CI 1.84-11.95, P = 0.001), moderate-severe diastolic dysfunction (OR = 2.71, 95\% CI 1.11-6.57, P = 0.028), and right ventricular (RV) dysfunction [reduced tricuspid annular plane systolic excursion < 17 mm (OR = 5.48, 95\% CI 2.12-14.13, P < 0.001), reduced RV fractional area change < 0.35 (OR = 3.32, 95\% CI 1.20-9.18, P = 0.021), and enlarged RV mid diameter (per 5 mm increase OR = 1.62, 95\% CI 1.12-2.34, P = 0.010)]. Reduced tricuspid annular plane systolic excursion (<17 mm) significantly associated with increased risk of LVT in anterior MI patients (OR = 3.84, 95\% CI 1.37-10.75, P = 0.010), especially in those patients without apical aneurysm (OR = 5.12, 95\% CI 1.45-18.08, P = 0.011), independent of body mass index, hypertension, anaemia, mitral annular plane systolic excursion, and moderate-severe diastolic dysfunction. Conclusions Right ventricular dysfunction as determined by reduced TAPSE or RV fractional area change is independently associated with LVT formation in acute anterior MI patients, especially in the setting of MI patients without the formation of an apical aneurysm. This study suggests that besides assessment of left ventricular abnormalities, assessment of concomitant RV dysfunction is of importance on risk stratification of LVT formation in patients with acute anterior MI.}, language = {en} } @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{KoepingShehataDielerCebullaetal.2017, author = {K{\"o}ping, Maria and Shehata-Dieler, Wafaa and Cebulla, Mario and Rak, Kristen and Oder, Daniel and M{\"u}ntze, Jonas and Nordbeck, Peter and Wanner, Christoph and Hagen, Rudolf and Schraven, Sebastian}, title = {Cardiac and renal dysfunction is associated with progressive hearing loss in patients with Fabry disease}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0188103}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169961}, pages = {e0188103}, year = {2017}, abstract = {Background Fabry disease (FD) is an X-linked recessive hereditary lysosomal storage disorder which results in the accumulation of globotriaosylceramid (Gb3) in tissues of kidney and heart as well as central and peripheral nervous system. Besides prominent renal and cardiac organ involvement, cochlear symptoms like high-frequency hearing loss and tinnitus are frequently found with yet no comprehensive data available in the literature. Objective To examine hearing loss in patients with FD depending on cardiac and renal function. Material and methods Single-center study with 68 FD patients enrolled between 2012 and 2016 at the Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery of the University of W{\"u}rzburg. Every subject underwent an oto-rhino-laryngological examination as well as behavioral, electrophysiological and electroacoustical audiological testing. High-frequency thresholds were evaluated by using a modified PTA\(_{6}\) (0.5, 1, 2, 4, 6, 8) and HF-PTA (6, 8 kHz). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class. Results Sensorineural hearing loss was detected in 58.8\% of the cohort, which occurred typically in sudden episodes and affected especially high frequencies. Hearing loss is asymmetric, beginning unilaterally and affecting the contralateral ear later. Tinnitus was reported by 41.2\%. Renal and cardiac impairment influenced the severity of hearing loss (p < 0.05). Conclusions High frequency hearing loss is a common problem in patients with FD. Although not life-threatening, it can seriously reduce quality of life and should be taken into account in diagnosis and therapy. Optimized extensive hearing assessment including higher frequency thresholds should be used.}, language = {en} } @article{SalingerHuLiuetal.2018, author = {Salinger, Tim and Hu, Kai and Liu, Dan and Taleh, Scharoch and Herrmann, Sebastian and Oder, Daniel and Gensler, Daniel and M{\"u}ntze, Jonas and Ertl, Georg and Lorenz, Kristina and Frantz, Stefan and Weidemann, Frank and Nordbeck, Peter}, title = {Association between Comorbidities and Progression of Transvalvular Pressure Gradients in Patients with Moderate and Severe Aortic Valve Stenosis}, series = {Cardiology Research and Practice}, journal = {Cardiology Research and Practice}, doi = {10.1155/2018/3713897}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227291}, pages = {3713897, 1-7}, year = {2018}, abstract = {Background. Fast progression of the transaortic mean gradient (P-mean) is relevant for clinical decision making of valve replacement in patients with moderate and severe aortic stenosis (AS) patients. However, there is currently little knowledge regarding the determinants affecting progression of transvalvular gradient in AS patients. Methods. This monocentric retrospective study included consecutive patients presenting with at least two transthoracic echocardiography examinations covering a time interval of one year or more between April 2006 and February 2016 and diagnosed as moderate or severe aortic stenosis at the final echocardiographic examination. Laboratory parameters, medication, and prevalence of eight known cardiac comorbidities and risk factors (hypertension, diabetes, coronary heart disease, peripheral artery occlusive disease, cerebrovascular disease, renal dysfunction, body mass index >= 30 Kg/m(2), and history of smoking) were analyzed. Patients were divided into slow (P-mean < 5 mmHg/year) or fast (P-mean >= 5 mmHg/year) progression groups. Results. A total of 402 patients (mean age 78 +/- 9.4 years, 58\% males) were included in the study. Mean follow-up duration was 3.4 +/- 1.9 years. The average number of cardiac comorbidities and risk factors was 3.1 +/- 1.6. Average number of cardiac comorbidities and risk factors was higher in patients in slow progression group than in fast progression group (3.3 +/- 1.5 vs 2.9 +/- 1.7; P = 0.036). Patients in slow progression group had more often coronary heart disease (49.2\% vs 33.6\%; P = 0.003) compared to patients in fast progression group. LDL-cholesterol values were lower in the slow progression group (100 +/- 32.6 mg/dl vs 110.8 +/- 36.6 mg/dl; P = 0.005). Conclusion. These findings suggest that disease progression of aortic valve stenosis is faster in patients with fewer cardiac comorbidities and risk factors, especially if they do not have coronary heart disease. Further prospective studies are warranted to investigate the outcome of patients with slow versus fast progression of transvalvular gradient with regards to comorbidities and risk factors.}, language = {en} } @article{KoepingShehataDielerSchneideretal.2018, author = {K{\"o}ping, Maria and Shehata-Dieler, Wafaa and Schneider, Dieter and Cebulla, Mario and Oder, Daniel and M{\"u}ntze, Jonas and Nordbeck, Peter and Wanner, Christoph and Hagen, Rudolf and Schraven, Sebastian P.}, title = {Characterization of vertigo and hearing loss in patients with Fabry disease}, series = {Orphanet Journal of Rare Diseases}, volume = {13}, journal = {Orphanet Journal of Rare Diseases}, doi = {10.1186/s13023-018-0882-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222818}, year = {2018}, abstract = {Background Fabry Disease (FD) is an X-linked hereditary lysosomal storage disorder which leads to a multisystemic intralysosomal accumulation of globotriaosylceramid (Gb3). Besides prominent renal and cardiac organ involvement, patients commonly complain about vestibulocochlear symptoms like high-frequency hearing loss, tinnitus and vertigo. However, comprehensive data especially on vertigo remain scarce. The aim of this study was to examine the prevalence and characteristics of vertigo and hearing loss in patients with FD, depending on renal and cardiac parameters and get hints about the site and the pattern of the lesions. Methods Single-center study with 57 FD patients. Every patient underwent an oto-rhino-laryngological examination as well as videonystagmography and vestibular evoked myogenic potentials (VEMPs) and audiological measurements using pure tone audiometry and auditory brainstem response audiometry (ABR). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class. Results More than one out of three patients (35.1\%) complained about hearing loss, 54.4\% about vertigo and 28.1\% about both symptom. In 74\% a sensorineural hearing loss of at least 25 dB was found, ABR could exclude any retrocochlear lesion. Caloric testing showed abnormal values in 71.9\%, VEMPs were pathological in 68\%. A correlation between the side or the shape of hearing loss and pathological vestibular testing could not be revealed. Conclusions Hearing loss and vertigo show a high prevalence in FD. While hearing loss seems due to a cochlear lesion, peripheral vestibular as well as central nervous pathologies cause vertigo. Thus, both the site of lesion and the pathophysiological patterns seem to differ.}, language = {en} } @article{KredelKunzmannSchlegeletal.2017, author = {Kredel, Markus and Kunzmann, Steffen and Schlegel, Paul-Gerhardt and W{\"o}lfl, Matthias and Nordbeck, Peter and B{\"u}hler, Christoph and Lotz, Christopher and Lepper, Philipp M. and Wirbelauer, Johannes and Roewer, Norbert and Muellenbach, Ralf M.}, title = {Double Peripheral Venous and Arterial Cannulation for Extracorporeal Membrane Oxygenation in Combined Septic and Cardiogenic Shock}, series = {American Journal of Case Reports}, volume = {18}, journal = {American Journal of Case Reports}, doi = {10.12659/AJCR.902485}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158193}, pages = {723-727}, year = {2017}, abstract = {Background: The use of venoarterial extracorporeal membrane oxygenation (va-ECMO) via peripheral cannulation for septic shock is limited by blood flow and increased afterload for the left ventricle. Case Report: A 15-year-old girl with acute myelogenous leukemia, suffering from severe septic and cardiogenic shock, was treated by venoarterial extracorporeal membrane oxygenation (va-ECMO). Sufficient extracorporeal blood flow matching the required oxygen demand could only be achieved by peripheral cannulation of both femoral arteries. Venous drainage was performed with a bicaval cannula inserted via the left V. femoralis. To accomplish left ventricular unloading, an additional drainage cannula was placed in the left atrium via percutaneous atrioseptostomy (va-va-ECMO). Cardiac function recovered and the girl was weaned from the ECMO on day 6. Successful allogenic stem cell transplantation took place 2 months later. Conclusions: In patients with vasoplegic septic shock and impaired cardiac contractility, double peripheral venoarterial extracorporeal membrane oxygenation (va-va-ECMO) with transseptal left atrial venting can by a lifesaving option.}, language = {en} } @article{LiuHuLauetal.2021, author = {Liu, Dan and Hu, Kai and Lau, Kolja and Kiwitz, Tobias and Robitzkat, Katharina and Hammel, Clara and Lengenfelder, Bj{\"o}rn Daniel and Ertl, Georg and Frantz, Stefan and Nordbeck, Peter}, title = {Impact of diastolic dysfunction on outcome in heart failure patients with mid-range or reduced ejection fraction}, series = {ESC Heart Failure}, volume = {8}, journal = {ESC Heart Failure}, number = {4}, doi = {10.1002/ehf2.13352}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258894}, pages = {2802-2815}, year = {2021}, abstract = {Aims The role of diastolic dysfunction (DD) in prognostic evaluation in heart failure (HF) patients with impaired systolic function remains unclear. We investigated the impact of echocardiography-defined DD on survival in HF patients with mid-range (HFmrEF, EF 41-49\%) and reduced ejection fraction (HFrEF, EF < 40\%). Methods and results A total of 2018 consecutive hospitalized HF patients were retrospectively included and divided in two groups based on baseline EF: HFmrEF group (n = 951, aged 69 ± 13 years, 74.2\% male) and HFrEF group (n = 1067, aged 68 ± 13 years, 76.3\% male). Clinical data were collected and analysed. All patients completed ≥1 year clinical follow-up. The primary endpoint was defined as all-cause death (including heart transplantation) and cardiovascular (CV)-related death. All-cause mortality (30.8\% vs. 24.9\%, P = 0.003) and CV mortality (19.1\% vs. 13.5\%, P = 0.001) were significantly higher in the HFrEF group than the HFmrEF group during follow-up [median 24 (13-36) months]. All-cause mortality increased in proportion to DD severity (mild, moderate, and severe) in either HFmrEF (17.1\%, 25.4\%, and 37.0\%, P < 0.001) or HFrEF (18.9\%, 30.3\%, and 39.2\%, P < 0.001) patients. The risk of all-cause mortality [hazard ratio (HR) = 1.347, P = 0.015] and CV mortality (HR = 1.508, P = 0.007) was significantly higher in HFrEF patients with severe DD compared with non-severe DD after adjustment for identified clinical and echocardiographic covariates. For HFmrEF patients, severe DD was independently associated with increased all-cause mortality (HR = 1.358, P = 0.046) but not with CV mortality (HR = 1.155, P = 0.469). Conclusions Echocardiography-defined severe DD is independently associated with increased all-cause mortality in patients with HFmrEF and HFrEF.}, language = {en} } @article{WagenhaeuserRickertSommeretal.2022, author = {Wagenh{\"a}user, Laura and Rickert, Vanessa and Sommer, Claudia and Wanner, Christoph and Nordbeck, Peter and Rost, Simone and {\"U}{\c{c}}eyler, Nurcan}, title = {X-chromosomal inactivation patterns in women with Fabry disease}, series = {Molecular Genetics \& Genomic Medicine}, volume = {10}, journal = {Molecular Genetics \& Genomic Medicine}, number = {9}, doi = {10.1002/mgg3.2029}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312795}, year = {2022}, abstract = {Background Although Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene (GLA), women may develop severe symptoms. We investigated X-chromosomal inactivation patterns (XCI) as a potential determinant of symptom severity in FD women. Patients and Methods We included 95 women with mutations in GLA (n = 18 with variants of unknown pathogenicity) and 50 related men, and collected mouth epithelial cells, venous blood, and skin fibroblasts for XCI analysis using the methylation status of the androgen receptor gene. The mutated X-chromosome was identified by comparison of samples from relatives. Patients underwent genotype categorization and deep clinical phenotyping of symptom severity. Results 43/95 (45\%) women carried mutations categorized as classic. The XCI pattern was skewed (i.e., ≥75:25\% distribution) in 6/87 (7\%) mouth epithelial cell samples, 31/88 (35\%) blood samples, and 9/27 (33\%) skin fibroblast samples. Clinical phenotype, α-galactosidase A (GAL) activity, and lyso-Gb3 levels did not show intergroup differences when stratified for X-chromosomal skewing and activity status of the mutated X-chromosome. Conclusions X-inactivation patterns alone do not reliably reflect the clinical phenotype of women with FD when investigated in biomaterial not directly affected by FD. However, while XCI patterns may vary between tissues, blood frequently shows skewing of XCI patterns.}, language = {en} } @article{HeidenreichWengDonhauseretal.2019, author = {Heidenreich, Julius F. and Weng, Andreas M. and Donhauser, Julian and Greiser, Andreas and Chow, Kelvin and Nordbeck, Peter and Bley, Thorsten A. and K{\"o}stler, Herbert}, title = {T1- and ECV-mapping in clinical routine at 3 T: differences between MOLLI, ShMOLLI and SASHA}, series = {BMC Medical Imaging}, volume = {19}, journal = {BMC Medical Imaging}, doi = {10.1186/s12880-019-0362-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201999}, pages = {59}, year = {2019}, abstract = {Background T1 mapping sequences such as MOLLI, ShMOLLI and SASHA make use of different technical approaches, bearing strengths and weaknesses. It is well known that obtained T1 relaxation times differ between the sequence techniques as well as between different hardware. Yet, T1 quantification is a promising tool for myocardial tissue characterization, disregarding the absence of established reference values. The purpose of this study was to evaluate the feasibility of native and post-contrast T1 mapping methods as well as ECV maps and its diagnostic benefits in a clinical environment when scanning patients with various cardiac diseases at 3 T. Methods Native and post-contrast T1 mapping data acquired on a 3 T full-body scanner using the three pulse sequences 5(3)3 MOLLI, ShMOLLI and SASHA in 19 patients with clinical indication for contrast enhanced MRI were compared. We analyzed global and segmental T1 relaxation times as well as respective extracellular volumes and compared the emerged differences between the used pulse sequences. Results T1 times acquired with MOLLI and ShMOLLI exhibited systematic T1 deviation compared to SASHA. Myocardial MOLLI T1 times were 19\% lower and ShMOLLI T1 times 25\% lower compared to SASHA. Native blood T1 times from MOLLI were 13\% lower than SASHA, while post-contrast MOLLI T1-times were only 5\% lower. ECV values exhibited comparably biased estimation with MOLLI and ShMOLLI compared to SASHA in good agreement with results reported in literature. Pathology-suspect segments were clearly differentiated from remote myocardium with all three sequences. Conclusion Myocardial T1 mapping yields systematically biased pre- and post-contrast T1 times depending on the applied pulse sequence. Additionally calculating ECV attenuates this bias, making MOLLI, ShMOLLI and SASHA better comparable. Therefore, myocardial T1 mapping is a powerful clinical tool for classification of soft tissue abnormalities in spite of the absence of established reference values.}, language = {en} } @article{TolstikAliGuoetal.2022, author = {Tolstik, Elen and Ali, Nairveen and Guo, Shuxia and Ebersbach, Paul and M{\"o}llmann, Dorothe and Arias-Loza, Paula and Dierks, Johann and Schuler, Irina and Freier, Erik and Debus, J{\"o}rg and Baba, Hideo A. and Nordbeck, Peter and Bocklitz, Thomas and Lorenz, Kristina}, title = {CARS imaging advances early diagnosis of cardiac manifestation of Fabry disease}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {10}, issn = {1422-0067}, doi = {10.3390/ijms23105345}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284427}, year = {2022}, abstract = {Vibrational spectroscopy can detect characteristic biomolecular signatures and thus has the potential to support diagnostics. Fabry disease (FD) is a lipid disorder disease that leads to accumulations of globotriaosylceramide in different organs, including the heart, which is particularly critical for the patient's prognosis. Effective treatment options are available if initiated at early disease stages, but many patients are late- or under-diagnosed. Since Coherent anti-Stokes Raman (CARS) imaging has a high sensitivity for lipid/protein shifts, we applied CARS as a diagnostic tool to assess cardiac FD manifestation in an FD mouse model. CARS measurements combined with multivariate data analysis, including image preprocessing followed by image clustering and data-driven modeling, allowed for differentiation between FD and control groups. Indeed, CARS identified shifts of lipid/protein content between the two groups in cardiac tissue visually and by subsequent automated bioinformatic discrimination with a mean sensitivity of 90-96\%. Of note, this genotype differentiation was successful at a very early time point during disease development when only kidneys are visibly affected by globotriaosylceramide depositions. Altogether, the sensitivity of CARS combined with multivariate analysis allows reliable diagnostic support of early FD organ manifestation and may thus improve diagnosis, prognosis, and possibly therapeutic monitoring of FD.}, language = {en} }