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Fischer A.,Goethe University Frankfurt | Fischer A.,Institute for Cardiovascular Regeneration | Roxe T.,Goethe University Frankfurt | Roxe T.,Institute for Cardiovascular Regeneration | And 10 more authors.
Circulation: Heart Failure | Year: 2012

Background-Chronic heart failure (CHF) is associated with a 4-fold increased risk for osteoporotic fractures. Therefore, we sought to identify the pathophysiological link between chronic heart failure and catabolic bone remodeling. Methods and Results-In a total cohort of 153 subjects (123 patients with CHF, 30 patients with coronary artery disease and preserved cardiac function) as well as mice with heart failure, bone marrow (BM) plasma levels of the catabolic receptor activator of NF-?B ligand (RANKL), and its antagonist, osteoprotegerin were measured. The osteoclast inducing activity of BM plasma was tested in cell culture. BM plasma levels of RANKL and of the ratio RANKL/osteoprotegerin were significantly elevated in patients with CHF. On multivariate regression analysis, parameters of severity and duration of heart failure were independent determinants of elevated BM plasma RANKL levels. BM plasma levels of RANKL were directly correlated with the systemic marker of bone turnover C-telopeptide of type 1 collagen (r=0.6; P<0.001). Alterations in BM plasma levels of RANKL/osteoprotegerin were confirmed in a mouse model of postinfarction heart failure. Stimulation of human mesenchymal cells with BM plasma obtained from CHF patients increased the formation of osteoclasts, and this effect was blocked by the RANKL inhibition. Conclusions-CHF is associated with a profound and selective elevation of the bone resorption stimulating RANKL within the BM microenvironment. These data for the first time disclose a direct pathophysiological pathway linking CHF with catabolic bone remodeling associated with an increased osteoporotic fracture risk. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifiers: NCT 00289822, NCT 00284713, NCT 00326989, NCT 00962364. © 2012 American Heart Association, Inc. Source

Gutjahr F.T.,University of Wurzburg | Gutjahr F.T.,Comprehensive Heart Failure Center | Kampf T.,University of Wurzburg | Winter P.,University of Wurzburg | And 6 more authors.
Magnetic Resonance in Medicine | Year: 2015

Purpose A method for the quantification of perfusion in murine myocardium is demonstrated. The method allows for the reconstruction of perfusion maps on arbitrary time points in the heart cycle while addressing problems that arise due to the irregular heart beat of mice. Methods A flow-sensitive alternating inversion recovery arterial spin labeling method using an untriggered FLASH-read out with random sampling is used. Look-Locker conditions are strictly maintained. No dummy pulses or mechanism to reduce deviation from Look-Locker conditions are needed. Electrocardiogram and respiratory data are recorded for retrospective gating and triggering. A model-based technique is used to reconstruct missing k-space data to cope with the undersampling inherent in retrospectively gated methods. Acquisition and reconstruction were validated numerically and in phantom measurements before in vivo experimentation. Results Quantitative perfusion maps were acquired within a single slice measurement time of 11 min. Perfusion values are in good accordance to literature values. Myocardial infarction could be clearly visualized and results were confirmed with histological results. Conclusion The proposed method is capable of producing quantitative perfusion maps on arbitrary positions in the heart cycle within a short measurement time. The method is robust against irregular breathing patterns and heart rate changes and can be implemented on all scanners. Magn Reson Med 74:1705-1715, 2015. © 2014 Wiley Periodicals, Inc. Source

Schmid J.,Medical University of Graz | Kaufmann R.,Medical University of Graz | Grubler M.R.,Medical University of Graz | Verheyen N.,Medical University of Graz | And 3 more authors.
Echocardiography | Year: 2016

Purpose: Myocardial strain and strain rate (SR) can be derived from either tissue Doppler (TDI) information or two-dimensional speckle tracking. As conventional TDI analysis (TDI-manual) is time-consuming with poor reproducibility, we developed a faster semiautomated approach (TDI-ST). We aimed to study the comparability of TDI-ST with TDI-manual, an established method for measuring strain and SR. Methods: Forty healthy subjects (mean age 38.3 ± 12.8 years) and 16 patients with FHL-1 cardiomyopathy (CMP) (36.8 ± 14.2 years) were analyzed with TDI-manual and TDI-ST. TDI-ST was performed with commercial software, using speckle tracking for myocardial tracking and TDI information to derive longitudinal strain and SR from high frame rate TDI recordings. Measurements of longitudinal systolic strain (S) and global S (GLS) made with the two methods were compared with Bland-Altman plots and Deming regression. Receiver operating characteristics (ROC) curves were used to compare discrimination between healthy individuals and patients. Results: Mean S was -20.11 ± 4.85% (healthy) and -16.12 ± 4.44% (CMP) with TDI-ST and -21.15 ± 5.68% (healthy) and -16.27 ± 6.44 (CMP) with TDI-manual. Using all measured segments, the mean bias was 0.78% strain toward less negative S with TDI-ST; the Deming regression slope was 0.7 for S and 0.9 for GLS. Intra- and inter-observer CVs were 5.4% and 7.0%, respectively. ROC curves showed no significant differences between the methods. Conclusion: The described S and SR measurements with TDI-ST are comparable to conventional manual analysis. Thus, using TDI-ST, it is possible to quickly and easily extract high-resolution deformation data. © 2015, Wiley Periodicals, Inc. Source

Ramos G.,Martin Luther University of Halle Wittenberg | Hofmann U.,Martin Luther University of Halle Wittenberg | Hofmann U.,Comprehensive Heart Failure Center | Frantz S.,Martin Luther University of Halle Wittenberg
Journal of Molecular and Cellular Cardiology | Year: 2016

Lymphocytes came recently into focus as modulators of non-infectious myocardial diseases. Several lines of experimental evidence now indicate that CD4+ T-cells can influence the healing and scarring processes that follow a myocardial infarction episode. Furthermore, such heart-directed T-cell activity has also been implicated in the pathogenesis cardiac remodeling that develops in response to chronic pressure-overload conditions. Mechanistically, different T-cell subsets can secrete several mediators and growth factors that influence the myocardial molecular milieu and directly interfere with the macrophages' and fibroblasts' activity. Therefore, the present review summarizes the current experimental evidence on the role of T-cells in myocardial scar formation after infarction and myocardial fibrosis as central mechanism of ventricular remodeling. © 2016 Elsevier Ltd. Source

Faller H.,University of Wurzburg | Stork S.,University of Wurzburg | Stork S.,Comprehensive Heart Failure Center | Gelbrich G.,University of Wurzburg | And 6 more authors.
Journal of Psychosomatic Research | Year: 2015

Objective: The prognostic potential of depressive symptoms independent of somatic features of heart failure severity has repeatedly been demonstrated. However, patient-reported functional status has rarely been accounted for in these studies. Thus, it has remained unclear to what extent the predictive power of depressive symptoms may mirror functional status. We therefore aimed to evaluate the prognostic value of depressive symptoms adjusting for patient-reported functional status in a large, well-characterized sample of patients with systolic heart failure. Methods: Eight hundred sixty-three patients, 67 ± 12. years old, 72% men, and 42% with New York Heart Association functional classes III/IV, who participated in the extended Interdisciplinary Network Heart Failure (INH) study were investigated. We assessed depressive symptoms using the Patient Health Questionnaire (PHQ-9) and patient-reported functional status with the Kansas City Cardiomyopathy Questionnaire (KCCQ). Data on survival was obtained after a follow-up of 18. months (100% complete). Results: Depressive symptoms predicted mortality risk (HR per PHQ-9 scale point = 1.07, 95% CI 1.04-1.09, p < .001), even after adjustment for heart failure severity and co-morbidities (HR = 1.04, 95% CI 1.01-1.07, p = .017). However, they were no longer significant predictors (HR = 1.01, 95% CI 0.98-1.05, p = 0.46) after additional adjustment for patient-reported functional status, which proved predictive of mortality risk (HR = 0.90, 95% CI 0.82-0.99, p = .025). Conclusion: Our results suggest that the association of depressive symptoms with functional status may at least partly explain the prognostic potential of depressive symptoms. © 2015 Elsevier Inc. Source

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