Hypertrophic cardiomyopathy in cardiac CT: a validation study on the detection of intramyocardial fibrosis in consecutive patients.

Hypertrophic Cardiomyopathy (HCM) confers a 4-5 %/year-risk for sudden cardiac death. Intramyocardial fibrosis (IF) is associated with this risk. The gold standard of IF visualization is cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE-CMR). In view of a number of CMR-limitations the hypothesis of this study was that late enhanced multi-slice computed tomography (leMDCT) enables demonstration of late enhancement (LE) indicating IF. In a prospective single-center validation study leMDCT research-scans were exclusively performed for IF-imaging in HCM-patients not including non-invasive coronary angiography during first-pass (64-slice; 80 kV; Iopromide, 150 mL, injected 7 min before scanning). Applying a 17-segment-polar-map short cardiac axis views (multiplanar reformations; 5 mm slice thickness) were analysed in order to exclude/detect, localize and measure LE practicing the manual quantification method if present. Finally, leMDCT and LGE-CMR data were unblinded for intermodal correlation. We included n = 24 patients consecutively (64.0 ± 14.5 years of age). LE was demonstrated by LGE-CMR in n = 14/24 patients (prevalence 58 %). Patient- and segment-based sensitivity in leMDCT was 100 and 68 %, respectively. In leMDCT tissue density of LE was 142 ± 51 versus 89.9 ± 19.3 HU in remote myocardium (p < 0.001). Signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR) appeared to be 7.3 ± 3.3 and 2.3 ± 1, respectively. Sizing of LE-area gave 2.2 ± 1.4 cm(2) in leMDCT versus 2.9 ± 2.4 cm(2) in LGE-CMR (r = 0.93). Intra-/interobserver variability was assessed with an accuracy of 0.36 cm(2) (r = 0.91) and 0.47 cm(2) (r = 0.82), respectively. In consecutive HCM patients leMDCT can reliably detect intramyocardial fibrosis marked by LE. In view of a comparatively low SNR and CNR leMDCT may alternatively be applied in case of CMR contraindications.

The cardiac Fas (APO-1/CD95) Receptor/Fas ligand system : relation to diastolic wall stress in volume-overload hypertrophy in vivo and activation of the transcription factor AP-1 in cardiac myocytes.

BACKGROUND: Fas (APO-1/CD95) is a transmembrane receptor belonging to the tumor necrosis factor receptor superfamily. Cross-linking of Fas by Fas ligand (FasL), a tumor necrosis factor-alpha-related cytokine, promotes apoptosis and/or transcription factor activation in a highly cell-type-specific manner. The biological consequences of Fas activation in cardiomyocytes and the regulation of Fas and FasL abundance in the myocardium in vivo remain largely unknown. METHODS AND RESULTS: As shown by immunohistochemistry, Fas was expressed on the sarcolemma of cardiomyocytes in left ventricular tissue sections. Moreover, FasL was constitutively expressed in the myocardium and in isolated cardiomyocytes, as revealed by reverse transcription polymerase chain reaction and Western blotting. Left ventricular abundance of Fas but not FasL was upregulated in a rat model of compensated volume-overload hypertrophy and was closely related to diastolic but not systolic wall stress as determined by MRI. Cardiomyocyte apoptosis was not enhanced in volume-overload hypertrophy despite the increased expression of Fas and the presence of FasL in the myocardium. Moreover, injection of mice with an agonistic anti-Fas antibody promoted hepatocyte but not cardiomyocyte apoptosis in vivo. Stimulation of isolated cardiomyocytes with recombinant FasL promoted an activation of the transcription factor AP-1 as shown by electrophoretic mobility shift assays but did not induce cell death. CONCLUSIONS: Fas and FasL are constitutively expressed in the myocardium and in cardiomyocytes. Myocardial expression of Fas is closely related to diastolic loading conditions in vivo. Signaling pathways emanating from Fas are coupled to an activation of the transcription factor AP-1 in cardiomyocytes.