Effect of spironolactone on endothelial function in patients with congestive heart failure on conventional medical therapy.

We prospectively studied the effect of spironolactone, an aldosterone antagonist, on endothelial function in patients with advanced congestive heart failure (CHF) using the brachial artery reactivity method. Twenty patients optimized on conventional CHF therapy were treated with spironolactone, and brachial artery flow- mediated dilation was measured at baseline and at 4 and 8 weeks. Spironolactone improved endothelial function at 4 weeks, and sustained the improvement at 8 weeks, in patients with CHF on conventional medical therapy, presumably due to reversal of aldosterone impairment of endothelial nitric oxide activity.

Novel indices for left-ventricular dyssynchrony characterization based on highly automated segmentation from real-time 3-d echocardiography.

Cardiac resynchronization therapy (CRT) using a biventricular pacemaker is an invasive and expensive treatment option for left ventricular mechanical dyssynchrony (LVMD). The CRT candidate selection is a crucial issue due to the unreliability of the current standard CRT indicators. Real-time three-dimensional (3-D) echocardiography (RT3DE) provides four-dimensional (4-D) (3-D+time) information about the LV and is suitable for LVMD assessment. In this article, the complex left ventricle (LV) shape and motion of 50 RT3DE datasets are represented by novel 4-D descriptors - 4-D sphericity, volume and shape, from which novel indices were derived by principal component analysis (PCA) and subsequently analyzed by a support vector machine (SVM) classifier to assess their capability of LVMD characterization and CRT outcome prediction. These novel indices outperformed clinical indices and have promising capabilities in disease characterization and great potential in CRT outcome prediction. To enable efficient quantitative RT3DE analysis, a segmentation method was developed to combine the powers of active shape models and optimal graph search. Various aspects of the method were designed to handle varying RT3DE image quality among datasets and LV segments. An application with graphical user interface was developed to provide the user with simple and intuitive control. The developed method was robust to inter-observer variability and produced very good accuracy - 3.2±1.1 mm absolute surface positioning error, <1 mm mean signed error and <5% mean volume difference. The computer method's classification performance was compared with the independent standard, showing that the 4-D shape modal indices were not only the most capable of all tested options when employed for disease characterization but also the least sensitive to segmentation imperfections.

Increased vascular alpha1-adrenergic sensitivity in patients with renal failure: receiving recombinant erythropoeitin.

End stage renal disease (ESRD) is associated with altered hemodynamic regulation as a result of the pathophysiology or treatment of renal failure. Hypertension, common among dialysis patients, is a recognized complication of recombinant human erythropoietin (rHuEPO) therapy. We determined vascular adrenergic and nitric-oxide-mediated responsiveness in 7 patients with established ESRD on rHuEPO treatment and in 13 healthy volunteers using the dorsal hand vein technique. Sensitivity to the alpha1-adrenergic selective agonist phenylephrine was significantly increased in patients with ESRD on rHuEPO. The mean dose of phenylephrine producing 50% venoconstriction (ED50) was 38 +/- 1.6 ng/min in patients with ESRD and 135 +/- 1.3 ng/min in healthy volunteers-almost a 4-fold increase in dose, P = 0.01. In contrast, maximal venodilation mediated by bradykinin, an endothelium-dependent vasodilator, was not different in the 2 groups. To determine whether rHuEPO has a direct vasoconstrictor effect, we studied venous responsiveness to local infusions of rHuEPO in healthy volunteers. Increasing concentrations of rHuEPO produced no vasoconstriction in hand veins of healthy volunteers. These results suggest that vascular responsiveness to alpha-adrenergic stimulation in patients with ESRD on rHuEPO is increased whereas bradykinin-mediated venodilation remains intact. This increase in vascular alpha-adrenergic responsiveness may contribute to the increased peripheral vascular resistance and hypertension seen in patients with ESRD on rHuEPO.

Validity of revised Doppler echocardiographic algorithms and composite clinical and angiographic data in diagnosis of diastolic dysfunction.

BACKGROUND: Commonly used echocardiographic indices for grading diastolic function predicated on mitral inflow Doppler analysis have a poor diagnostic concordance and discriminatory value. Even when combined with other indices, significant overlap prevents a single group assignment for many subjects. We tested the relative validity of echocardiographic and clinical algorithms for grading diastolic function in patients undergoing cardiac catheterization. METHOD: Patients (n = 115), had echocardiograms immediately prior to measuring left ventricular (LV) diastolic (pre-A, mean, end-diastolic) pressures. Diastolic function was classified into the traditional four stages, and into three stages using a new classification that obviates the pseudonormal class. Summative clinical and angiographic data were used in a standardized fashion to classify each patient according to the probability for abnormal diastolic function. Measured LV diastolic pressure in each patient was compared with expected diastolic pressures based on the clinical and echocardiographic classifications. RESULT: The group means of the diastolic pressures were identical in patients stratified by four-stage or three-stage echocardiographic classifications, indicating that both classifications schemes are interchangeable. When severe diastolic dysfunction is diagnosed by the three-stage classification, 88% and 12%, respectively, were clinically classified as high and intermediate probability, and the mean LV pre-A pressures was >12 mmHg (P < 0.005). Conversely, the mean LV pre-A pressure in the clinical low probability or echocardiographic normal groups was <11 mmHg. CONCLUSION: Use of a standardized clinical algorithm to define the probability of diastolic function identifies patients with elevated LV filing pressure to the same extent as echocardiographic methods.