Echocardiography: future developments. What is diastole and how to assess it? Impaired left ventricular systolic function.

Epidemiologic data show that diastolic heart failure is responsible for 38% to 54% of all heart failure cases. Left ventricular diastolic function can be characterized invasively in the catheter laboratory and non-invasively by echocardiography. Although echocardiography does not directly measure hemodynamic parameters, it is the most practical routine clinical approach for the evaluation of left ventricular diastolic function with given clinical and experimental evidence supporting its use as well as its safety, versatility, and portability. A set of echocardiographic paramters suitable for the description of diastolic function has been investigated or is still under investigation. Two guideline-papers exist with regard to the assessment of diastolic function, diastolic dysfunction and diastolic heart failure. Mitral inflow pattern, isovolumetric relaxation time, flow propagation velocity, tissue Doppler imaging and pulmonary vein flow pattern are central parameters established for the assessment of diastolic function, estimation of left atrial pressure and left ventricular enddiastolic pressure. Furthermore, calculated parameters, e.g. like E/E´, E/Vp, AR-A, for a more accurate determination of diastolic dysfunction have been evaluated. With respect to recent guidelines and recommendations, this review summarizes the physiology and pathophysiology of diastole, current echocardiographic methods and calculated echocardiographic parameters for the assessment of left ventricular diastolic function and dysfunction. In addition, an overview of the current state of research with regard to the echocardiographic assessment of left ventricular diastolic function will be given.

Serial NT-proBNP measurements for risk stratification of patients with decompensated heart failure.

PURPOSE: NT-proBNP is an important prognostic predictor in patients with heart failure. However, it is unknown whether a change of NT-proBNP plasma levels in the early phase of decompensation might be of additional prognostic value in patients with acute decompensation of heart failure. METHODS AND RESULTS: NT-proBNP plasma levels of 116 patients with decompensated heart failure from ischemic/non-ischemic origin were measured at baseline and at 12, 24 and 48 h after hospital admission. Baseline levels and changes of plasma levels within the first 48 h were correlated with 30-day mortality. In all patients, NT-proBNP 12 h after admission was highest and superior with respect to the prediction of 30-day mortality compared to plasma levels on admission. In total, 38 patients died within the first 30 days. In these patients absolute NT-proBNP plasma levels were significantly higher and the increase within 12 h after admission was more pronounced compared to survivors (p<0.001). NT-proBNP at 12 h after admission also had the highest predictive value for the 30-day mortality rate in patients with acute myocardial infarction. The increase of NT-proBNP plasma levels within 12 h after admission had the highest predictive value in patients suffering from decompensated heart failure. CONCLUSIONS: NT-proBNP is a powerful marker of 30-day mortality in patients with decompensated heart failure of ischemic and non-ischemic origin. Compared with single baseline measurements, serial measurements of NT-proBNP plasma levels within 12 h after hospital admission may be used to increase the predictive value of NT-proBNP with regard to the early identification of patients who are at high risk of mortality.

Comparison of the hepatic clearances of campesterol, sitosterol, and cholesterol in healthy subjects suggests that efflux transporters controlling intestinal sterol absorption also regulate biliary secretion.

BACKGROUND: Recently identified ABCG5/8 transporters are responsible in part for the different absorption rates of campesterol, sitosterol, and cholesterol. These transporters are also expressed in the liver and might regulate biliary sterol secretion. AIMS: This study was therefore conducted to determine the biliary secretion rates and hepatic clearances of campesterol, sitosterol, and cholesterol. SUBJECTS: Six healthy, male volunteers. METHODS: Deuterium labelled sitosterol and campesterol, and unlabelled sitostanol were constantly infused together with a liquid formula using a duodenal perfusion technique. Biliary secretion and hepatic clearance rates were calculated from hourly bile and plasma samples. RESULTS: Plasma concentrations of cholesterol, campesterol, and sitosterol averaged 167.5 (50) mg/dl (SD), 0.50 (0.22) mg/dl, and 0.30 (0.10) mg/dl, respectively. Sitosterol showed a significantly higher biliary secretion rate (1.23 (0.87) mg/h) than campesterol (0.76 (0.54) mg/h, p=0.0321), but both plant sterols had significantly lower biliary secretion rates compared with cholesterol (47.7 (17.5) mg/h; p=0.001 for both). Hepatic clearance of cholesterol (0.31 (0.18) dl/h) was significantly lower compared with campesterol (2.11 (2.51) dl/h) and sitosterol (4.97 (4.70) dl/h; p=0.028 for both), and the clearance of campesterol was significant lower compared with sitosterol (p=0.028). CONCLUSION: The observed inverse relation between hepatic clearance and known intestinal absorption of cholesterol, campesterol, and sitosterol supports the hypothesis that the ABCG5/8 transporters regulating intestinal sterol absorption might also be involved in biliary sterol excretion.

Neuropeptide Y and peptide YY, but not pancreatic polypeptide, substance P, cholecystokinin and gastric inhibitory polypeptide, inhibit the glucagon- and noradrenaline-dependent increase in glucose output in rat liver.

OBJECTIVE: The gastrointestinal peptides neuropeptide Y (NPY), peptide YY (PYY), pancreatic polypeptide (PP), substance P (SP), cholecystokinin (CCK) and gastric inhibitory polypeptide (GIP) are released into the portal vein mainly during the absorptive phase. Their direct actions and their hormone modulatory effects on liver carbohydrate metabolism were investigated. METHODS: Isolated rat liver, single-pass-perfused via both the hepatic artery (120 cm H2O, 30% flow) and the portal vein (20 cm H2O, 70% flow) with a Krebs-Henseleit buffer containing 5 mM glucose, 2 mM lactate and 0.2 mM pyruvate, NPY (5 nM), PYY (5 nM), PP (5 nM), SP (100 nM), CCK (100 nM) and GIP (10 nM) was infused for 10 min via either vessel. In additional experiments, insulin (100 nM), glucagon (1 nM) or noradrenaline (1 microM) were applied for 5 min via the portal vein during a 20 min portovenous infusion of one of the peptides. RESULTS: Under basal conditions, neither arterial nor portal NPY, PYY, PP, SP, CCK or GIP modified hepatic glucose and lactate metabolism. Also, none of the peptides enabled an action of portal insulin in the normally insulin-insensitive isolated perfused rat liver. NPY and PYY, but not PP, SP, CCK or GIP, inhibited the increase in glucose release by glucagon and noradrenaline. Under basal conditions, none of the peptides altered hepatic flow. Only portal NPY and PYY enhanced slightly the noradrenaline-dependent reduction of portal flow. CONCLUSIONS: NPY, PYY, PP, SP, CCK and GIP do not act directly as regulators of basal hepatic carbohydrate metabolism. NPY and PYY act as signal factors of the absorptive phase function as antagonists of the postabsorptive glucose regulatory hormones glucagon and noradrenaline.

The low-dose monoethylglycinexylidide test: assessment of liver function with fewer side effects.

The hepatic metabolism of lidocaine (1 mg/kg intravenously) to its metabolite monoethylglycinexylidide (MEG-X) is the basis of the standard MEG-X test. To reduce the lidocaine-induced side effects, we evaluated the MEG-X formation after 0.5 and 1 mg/kg lidocaine intravenously in subjects with normal (n = 5) and severely impaired liver function (n = 7) (study I). From this study, a low-dose test (MEG-X concentration 30 minutes after 50 mg lidocaine intravenously [MEG-X30min] normalized to standard MEG-X test results) was developed. Sensory side effects from this low dose and from the standard MEG-X test were compared in a double-blind, randomized, cross-over study (study II) comprising 15 individuals with normal liver function and 45 patients with cirrhosis (15 Child A, 15 Child B, and 15 Child C). In study I, MEG-X formation rate was dose-independent in patients with severely impaired liver function. In study II, normalized MEG-X test results (ranging from < or = 4 to 120 microg/L) were virtually identical to the standard test results (mean difference: -1.9 microg/L; 95% confidence interval [CI]: -5.3; 1.5 microg/L). Fewer individuals experienced side effects (30% vs. 53%) with the low-dose test (P = .0013). In a multivariate analysis, the Child-Pugh score was inversely related to the occurrence of side effects. The low-dose MEG-X test gives almost identical results to the standard MEG-X test and is associated with fewer side effects, which occur less often in individuals with more severely compromised liver function.