@article{GramGenslerAlbertovaetal.2022,
  author    = {Gram, Maximilian and Gensler, Daniel and Albertova, Petra and Gutjahr, Fabian Tobias and Lau, Kolja and Arias-Loza, Paula-Anahi and Jakob, Peter Michael and Nordbeck, Peter},
  title     = {Quantification correction for free-breathing myocardial T1ρ mapping in mice using a recursively derived description of a T\(_{1p}\)\(^{*}\) relaxation pathway},
  series = {Journal of Cardiovascular Magnetic Resonance},
  volume    = {24},
  journal   = {Journal of Cardiovascular Magnetic Resonance},
  number    = {1},
  doi       = {10.1186/s12968-022-00864-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300491},
  year      = {2022},
  abstract  = {Background Fast and accurate T1ρ mapping in myocardium is still a major challenge, particularly in small animal models. The complex sequence design owing to electrocardiogram and respiratory gating leads to quantification errors in in vivo experiments, due to variations of the T\(_{1p}\) relaxation pathway. In this study, we present an improved quantification method for T\(_{1p}\) using a newly derived formalism of a T\(_{1p}\)\(^{*}\) relaxation pathway. Methods The new signal equation was derived by solving a recursion problem for spin-lock prepared fast gradient echo readouts. Based on Bloch simulations, we compared quantification errors using the common monoexponential model and our corrected model. The method was validated in phantom experiments and tested in vivo for myocardial T\(_{1p}\) mapping in mice. Here, the impact of the breath dependent spin recovery time T\(_{rec}\) on the quantification results was examined in detail. Results Simulations indicate that a correction is necessary, since systematically underestimated values are measured under in vivo conditions. In the phantom study, the mean quantification error could be reduced from - 7.4\% to - 0.97\%. In vivo, a correlation of uncorrected T\(_{1p}\) with the respiratory cycle was observed. Using the newly derived correction method, this correlation was significantly reduced from r = 0.708 (p < 0.001) to r = 0.204 and the standard deviation of left ventricular T\(_{1p}\) values in different animals was reduced by at least 39\%. Conclusion The suggested quantification formalism enables fast and precise myocardial T\(_{1p}\) quantification for small animals during free breathing and can improve the comparability of study results. Our new technique offers a reasonable tool for assessing myocardial diseases, since pathologies that cause a change in heart or breathing rates do not lead to systematic misinterpretations. Besides, the derived signal equation can be used for sequence optimization or for subsequent correction of prior study results.},
  language  = {en}
}
@article{LauUeceylerCairnsetal.2022,
  author    = {Lau, Kolja and {\"U}{\c{c}}eyler, Nurcan and Cairns, Tereza and Lorenz, Lora and Sommer, Claudia and Schindeh{\"u}tte, Magnus and Amann, Kerstin and Wanner, Christoph and Nordbeck, Peter},
  title     = {Gene variants of unknown significance in Fabry disease: Clinical characteristics of c.376AG (p.Ser126Gly)},
  series = {Molecular Genetics \& Genomic Medicine},
  volume    = {10},
  journal   = {Molecular Genetics \& Genomic Medicine},
  number    = {5},
  doi       = {10.1002/mgg3.1912},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312817},
  year      = {2022},
  abstract  = {Background Anderson-Fabry disease (FD) is an X-linked lysosomal storage disorder with varying organ involvement and symptoms, depending on the underlying mutation in the alpha-galactosidase A gene (HGNC: GLA). With genetic testing becoming more readily available, it is crucial to precisely evaluate pathogenicity of each genetic variant, in order to determine whether there is or might be not a need for FD-specific therapy in affected patients and relatives at the time point of presentation or in the future. Methods This case series investigates the clinical impact of the specific GLA gene variant c.376A>G (p.Ser126Gly) in five (one heterozygous and one homozygous female, three males) individuals from different families, who visited our center between 2009 and 2021. Comprehensive neurological, nephrological and cardiac examinations were performed in all cases. One patient received a follow-up examination after 12 years. Results Index events leading to suspicion of FD were mainly unspecific neurological symptoms. However, FD-specific biomarkers, imaging examinations (i.e., brain MRI, heart MRI), and tissue-specific diagnostics, including kidney and skin biopsies, did not reveal evidence for FD-specific symptoms or organ involvement but showed normal results in all cases. This includes findings from 12-year follow-up in one patient with renal biopsy. Conclusion These findings suggest that p.Ser126Gly represents a benign GLA gene variant which per se does not cause FD. Precise clinical evaluation in individuals diagnosed with genetic variations of unknown significance should be performed to distinguish common symptoms broadly prevalent in the general population from those secondary to FD.},
  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}
}