Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction.

BACKGROUND: The pathophysiology of heart failure with normal ejection fraction (HFNEF) is still under discussion. Here we report the influence of cardiac inflammation on extracellular matrix (ECM) remodeling in patients with HFNEF. METHODS AND RESULTS: We investigated left ventricular systolic and diastolic function in 20 patients with HFNEF and 8 control patients by conductance catheter methods and echocardiography. Endomyocardial biopsy samples were also obtained, and ECM proteins as well as cardiac inflammatory cells were investigated. Primary human cardiac fibroblasts were outgrown from the endomyocardial biopsy samples to investigate the gene expression of ECM proteins after stimulation with transforming growth factor-ß. Diastolic dysfunction was present in the HFNEF patients compared with the control patients. In endomyocardial biopsy samples from HFNEF patients, we found an accumulation of cardiac collagen, which was accompanied by a decrease in the major collagenase system (matrix metalloproteinase-1) in the heart. Moreover, a subset of inflammatory cells, which expressed the profibrotic growth factor transforming growth factor-ß, could be documented in the HFNEF patients. Stimulation of primary human cardiac fibroblasts from HFNEF patients with transforming growth factor-ß resulted in transdifferentiation of fibroblasts to myofibroblasts, which produced more collagen and decreased the amount of matrix metalloproteinase-1, the major collagenase in the human heart. A positive correlation between cardiac collagen, as well as the amount of inflammatory cells, and diastolic dysfunction was evident and suggests a direct influence of inflammation on fibrosis triggering diastolic dysfunction. CONCLUSIONS: Cardiac inflammation contributes to diastolic dysfunction in HFNEF by triggering the accumulation of ECM.

[The role of whole body spiral CT in the primary work-up of polytrauma patients--comparison with conventional radiography and abdominal sonography]. / Die Rolle der Granzköper-Spiral-CT bei der Primärdiagnostik polytraumatisierter Patienten -- Vergleich mit konventioneller Radiographie und Abdomensonographie.

PURPOSE: To evaluate the role of routine "whole body spiral CT"in the primary work-up of polytrauma patients for injuries of the thorax, abdomen and spine, and to compare the results with those of conventional radiography of the chest and spine and abdominal ultrasound. MATERIALS AND METHODS: Fifty consecutive polytrauma patients underwent contrast-enhanced single slice spiral CT (5 mm collimation) from the vertex to the floor of the pelvis as part of the primary work-up after emergency room admission. Overlapping high resolution sections and sagittal reformations of the spine were obtained. Reports of additional chest radiographs (n=43), abdominal ultrasound examinations(n = 47) and spine radiographs (n = 36) performed in the emergency room were available for retrospective comparison. The "final diagnoses," which served as the standard of reference, were taken from the patients' records using all information that be-came available until discharge or death, such as findings from further imaging, surgery and autopsy. RESULTS: CT showed 109(97%) of 112 thoracic and abdominal soft-tissue injuries. Relevant injuries missed were an early splenic laceration and an early pelvic hematoma, both of which became clinically apparent several hours later. There were 4 false positive CT findings. Conventional chest radiography demonstrated only 20% of thoracic and sonography 22% of abdominal injuries. Chest radiography and sonography produced 2 false-positive findings each. CT showed 66 (87%) of 76 vertebral fractures including all 19 unstable ones.CT missed 5 anterior vertebral body and 5 spinous/transverse process fractures. Conventional radiography found 71 % of vertebral fractures including only 50 % of the unstable ones. CONCLUSION: Routine performance of whole body spiral CT as part of the primary work-up of polytrauma patients provides a fast and comprehensive survey and detects almost all soft tissue injuries of the chest and abdomen. It is clearly superior to chest radiography and abdominal sonography. All spinal injuries relevant for the acute management were also seen on CT, but not on conventional radiography.