In vivo thrombin generation and activity during and after intravenous infusion of heparin or recombinant hirudin in patients with unstable angina pectoris.

In patients with unstable angina, intravenous heparin reduces thrombin activity but does not influence thrombin generation. Recombinant hirudin, a direct thrombin inhibitor, may be more effective in inhibiting both thrombin generation and activity. We measured the plasma levels of prothrombin fragment 1+2 (a marker of thrombin generation) and fibrinopeptide A (a marker of thrombin activity) in 67 patients with unstable angina enrolled in the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) IIb trial who were receiving either recombinant hirudin (31 patients) or heparin (36 patients). Blood samples were obtained at baseline (before any treatment), after 3 to 5 days of study drug infusion (immediately before discontinuation), and 1 month later. In the patients receiving recombinant hirudin, the prothrombin fragment 1+2 levels measured immediately before drug discontinuation were significantly lower than at baseline (P:=0.0014), whereas they had not changed in the patients receiving heparin; at this time point, the difference between patients receiving hirudin and those receiving heparin was statistically significant (P:=0.032). One month later, the prothrombin fragment 1+2 levels in both groups were similarly persistently high and did not differ from baseline. Fibrinopeptide A plasma levels at the end of infusion were significantly lower than at baseline in both treatment groups (P:=0. 0005 for hirudin and P:=0.042 for heparin) and remained lower after 1 month (P:=0.0001 for both hirudin and heparin). The fibrinopeptide A plasma levels were not different between patients treated with hirudin versus heparin at baseline, at the end of infusion, and after 1 month. Thus, in patients with unstable angina, in vivo thrombin generation and activity are reduced during intravenous infusion of recombinant hirudin. However, the inhibition of thrombin generation is not sustained, and after 1 month, the majority of patients have biochemical signs of increased thrombin generation.

Evaluation of regional left ventricular wall motion with color kinesis: comparison with two-dimensional echocardiography in patients after acute myocardial infarction.

BACKGROUND: Color kinesis (CK) is a new echocardiographic technique for the assessment of left ventricular (LV) wall motion based on acoustic quantification. Using integrated backscatter data, this technique identifies the pixel value transitions from blood to myocardial tissue throughout systole and tracks endocardial motion in real time. The color-encoded images, built on a frame-by-frame basis by adding one color at a time, provide an integrated display of the timing and amplitude of endocardial motion in a single end-systolic frame. Recent studies have shown that CK is a promising clinical tool for quantitative assessment of regional LV function. OBJECTIVES: The aim of this study was to evaluate the feasibility and accuracy of CK in identifying the regional wall-motion abnormalities diagnosed by conventional two-dimensional (2-D) echocardiography in patients after acute myocardial infarction (AMI). METHODS: The end-systolic color overlays were analyzed using a method to quantify the regional timing and amplitude of endocardial systolic excursion (ESE) based on the count of the numbers of colors. At this point, the total duration (ESE timing) and distance (ESE amplitude) of endocardial excursion from end-diastolic to end-systolic color-frame was calculated in each segment. In 54 patients after AMI, we compared the feasibility and ability of CK superimposed on 2-D superimposed on 2-D superimposed on 2-D echocardiographic images and visual 2-D echo analysis to evaluate the endocardial border excursion in parasternal short-axis (SAX) and apical four-(AP4CH) and two-(AP2CH) chamber views. In 20 normal subjects, the end-systolic color overlays were used to evaluate the variability of the measurements of ESE timing (msec) and amplitude (cm) and to define the reference values. Image quality was considered adequate if at least 12 of 16 segments could be evaluated for systolic function by conventional visual 2-D echo. Among 54 patients, 35 with adequate studies were selected to determine the accuracy of quantitative analysis of CK images in identifying regional wall-motion abnormalities. RESULTS: The SAX view was obtained in 36 of 54 patients; of the possible 216 segments, 210 (97%) were adequately visualized by 2-D echocardiography and 207 (96%) by CK. Apical views were obtained in 50 patients (93%); of the possible 300 segments, 93% were visualized by 2-D echocardiography and 90% by CK in the AP4CH view and 94% and 92%, respectively, were visualized by the two methods in the AP2CH view. In normal subjects, measurements of ESE timing and amplitude were found to be consistent and the mean values were 346 msec (range 280-360) and 0.99 cm (range 0.72-1.26) respectively. In the 35 selected patients, 2-D echocardiography identified 355 normokinetic segments in which ESE timing and amplitude were similar to the reference values. In 83 hypokinetic segments and 108 akinetic segments, ESE timing and amplitude were significantly inferior to values of normokinetic segments (p < 0.001). An ESE timing below the reference values of 280 msec identified all of the 191 asynergic segments (sensitivity and specificity = 100%) and an ESE amplitude of less than 0.70 cm identified 188 asynergic segments (sensitivity = 98% and specificity = 99%). CONCLUSIONS: CK showed good feasibility and diagnostic accuracy in identifying regional wall motion abnormalities in patients with acute myocardial infarction. The model used in our study for the quantitative analysis of color kinesis images, which provided easy and feasible indices of timing and amplitude of endocardial excursion, enabled fast and objective evaluation of LV regional wall motion.