Acute aortic dissection presents with a wide range of manifestations, and classic findings are often absent. A high clinical index of suspicion is necessary. Despite recent advances, in-hospital mortality rates remain high. Our data support the need for continued improvement in prevention, diagnosis, and management of acute aortic dissection.

Background: Multi-marker risk scores accurately predict prognosis in heart failure patients but calculation is complex. Aims: To compare the prognostic accuracy of the Seattle Heart Failure Survival Score (SHFS) and a model derived from the CHARM programme, with laboratory parameters NT-proBNP and glomerular filtration rate (GFR). Methods and results:In a sample of 290 heart failure patients, 39 patients died, 22 were hospitalised with acute heart failure and 4 underwent urgent cardiac transplantation during a median follow-up of 498 days. NT-proBNP, GFR, CHARM and SHFS showed an AUC for an endpoint during 1-year of 0.80, 0.72, 0.79 and 0.69, respectively. The hazard ratio for an endpoint during follow-up was 2.1, 2.6, 1.9 and 2.1 per 1 SD increase of log NT-proBNP and CHARM and per 1 SD decrease of GFR and SHFS, respectively. In multivariate analysis, log NTproBNP and GFR added independent prognostic information to CHARM and SHFS, respectively. Conclusion: NT-proBNP and GFR independently predicted endpoint-free survival in systolic heart failure patients, with NT-proBNP being superior and equally predictive to the SHFS and CHARM score, respectively. Assessment of both laboratory markers can simplify prognostic stratification, addition to multi-marker scores should be evaluated.

Background: Cardiac hypertrophy may initiate progression to a compromised cardiac function. While the clinical consequences of hypertrophy are well understood, only little is known about the underlying molecular pathways. As reported from animal experiments, the Ca -calmodulin activated phosphatase calcineurin and its downstream transcriptional effector NFAT have been 2q implicated as transducers of the hypertrophic response. Methods and results: To study whether the calcineurin pathway is activated in human heart failure, we investigated samples of human left ventricular myocardium from patients with dilated (idiopathic) cardiomyopathy (DCM, NYHA IV, ns8) in comparison with non-failing controls (NF, ns8). We not only analyzed the pathway by measuring the calcineurin activity, but also by determination of the protein expression of the calcineurin B subunit and additional key markers of the calcineurin signaling cascade (NFAT-3, GATA-4). Calcineurin enzymatic activity was increased by 80% in human dilated cardiomyopathy compared with non-failing human hearts (135.424"11.69 and 83.484"1.81 nmol Piymin per ml). This was in line with increased protein expression of calcineurin B in DCM (71.18q9.11 vs. 46.41"11.23 densitometric units (DU)ymg protein). In order to verify the activated calcineurin pathway as described in animal models, we compared the protein expression of NFAT-3 in homogenates within nuclear extracts. In nuclear extracts the protein level of NFAT-3 was increased in dilated cardiomyopathy compared with non-failing myocardium (104.01"8.85 vs. 71.47"8.79 DUymg protein). In contrast, in homogenates the expression of NFAT-3 was higher in the non-failing tissue indicating subcellular redistribution (19.56"3.36 vs. 25.84"3.16 DUymg protein). The protein expression of GATA-4 was increased in DCM (43.14"2.89 vs. 29.87"2.17 DUymg protein). Conclusions: In human heart failure (DCM) the calcineurin signaling pathway is activated not only by an increased activity of calcineurin and expression of GATA-4, but also by the shift from dephosphorylated NFAT-3 to the nucleus indicating subcellular redistribution and regulatory activation.

Pressure overload is the major stimulus for cardiac hypertrophy. Accumulating evidence suggests an important role for calcium-induced activation of calcineurin in mediating hypertrophic signaling. Hypertrophy is an important risk factor for cardiovascular morbidity and mortality. We therefore employed an in vitro mechanical stretch model of cultured neonatal cardiomyocytes to evaluate proposed mechanisms of calcium-induced calcineurin activation in terms of inhibition of calcineurin activity and hypertrophy. The protein/DNA ratio and ANP gene expression were used as markers for stretch-induced hypertrophy. Stretch increased the calcineurin activity, MCIP1 gene expression and DNA binding of NFATc as well as the protein/DNA ratio and ANP mRNA in a significant manner. The specific inhibitor of calcineurin, cyclosporin A, inhibited the stretch-induced increase in calcineurin activity, MCIP1 gene expression and hypertrophy. The L-type Ca²⁺ channel blocker nifedipine and a blocker of the Na⁺/H⁺ exchanger (cariporide) both suppressed stretch-dependent enhanced calcineurin activity and hypertrophy. Also application of a blocker of the Na⁺/Ca²⁺ exchanger (KB-R7943) was effective in preventing calcineurin activation and increases in the protein/DNA ratio. Inhibition of capacitative Ca²⁺ entry with SKF 96365 was also sufficient to abrogate calcineurin activation and hypertrophy. The blocker of stretch-activated ion channels, streptomycin, was without effect on stretch-induced hypertrophy and calcineurin activity. The present work suggests that of the proposed mechanisms for the calcium-induced activation of calcineurin (L-type Ca²⁺ channels, capacitative Ca²⁺ entry, Na⁺/H⁺ exchanger, Na⁺/Ca²⁺ exchanger and stretch-activated channels) all but stretch-activated channels are possible targets for the inhibition of hypertrophy.

Background: Spinal cord electrical stimulation (SCS) has shown to be a treatment option for patients suffering from angina pectoris CCS III-IV although being on optimal medication and not suitable for conventional treatment strategies, e.g. CABG or PTCA. Although many studies demonstrated a clear symptomatic relief under SCS therapy, there are only a few short-term studies that investigated alterations in cardiac ischemia. Therefore doubts remain whether SCS has a direct effect on myocardial perfusion.