An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study).

Maximal benefits of coronary reperfusion after acute myocardial infarction (AMI) with ST-segment elevation may be attenuated by neutrophil-mediated reperfusion injury. Inflammatory mediators released from potentially viable myocytes cause activation of neutrophils, which traverse the endothelium and enter the myocardium. This process involves interaction between the neutrophil-expressed CD11/CD18 and endothelial-expressed intercellular adhesion molecule-1 (ICAM-1). Preclinical studies have shown that monoclonal antibodies (MAb) to CD18 can limit infarct size and preserve left ventricular function. We sought to determine the initial clinical safety and tolerability of Hu23F2G (LeukArrest), a humanized MAb to CD11/CD18, in patients with AMI who underwent percutaneous transluminal coronary angioplasty (PTCA). Sixty patients with AMI were randomized to low- (0.3 mg/kg) or high-dose (1.0 mg/kg) Hu23F2G or to placebo immediately before PTCA. We found no clinically significant differences in vital signs, physical examination, laboratory evaluation, or need for subsequent cardiac interventions. In Hu23F2G treatment groups, serum concentration of Hu23F2G increased rapidly to 3,234 +/- 1,298 microg/L (low-dose group) and 15,558 +/- 4409 microg/L (high-dose group) between 5 and 60 minutes, then declined over 72 hours to near-baseline values. Myocardial single-photon emission computed tomographic imaging 120 to 260 hours after PTCA showed no statistically significant differences in final left ventricular defect size. Hu23F2G was well tolerated, with no increase in adverse events, including infections. Thus, Hu23F2G appears safe and well tolerated in patients undergoing PTCA for AMI.

Ultrasonic tissue characterization with integrated backscatter. Acute myocardial ischemia, reperfusion, and stunned myocardium in patients.

We have previously shown in studies of experimental animals that myocardium exhibits a cardiac cycle-dependent variation of integrated backscatter that reflects regional myocardial contractile performance and that is blunted promptly after arterial occlusion and recovers after reperfusion. To define the clinical utility of ultrasonic tissue characterization with integrated backscatter for detection of acute myocardial infarction and reperfusion, 21 patients (14 men and seven women) were studied in the cardiac care unit within the first 24 hours (mean time, 11.3 hours; range, 3.5-23.8 hours) after the onset of symptoms indicative of acute myocardial infarction with conventional two-dimensional and M-mode echocardiography and with analysis of integrated backscatter. The magnitude of cyclic variation of integrated backscatter was measured from several sites within acute infarct regions and normal regions remote from the infarct zone for each patient. The average magnitude of cyclic variation among all patients (n = 21) was 4.8 +/- 0.5 dB in normal regions compared with 0.8 +/- 0.3 dB in infarct regions (p less than 0.05) within the first 24 hours after the onset of symptoms. Among the patients who had two studies, 15 (mean, 7.1 days; range, 2-31 days for second study) underwent coronary arteriography to define vessel patency. In patients with vessels with documented patency (n = 10), the magnitude of cyclic variation in infarct regions increased over time from 1.3 +/- 0.6 to 2.5 +/- 0.5 dB from the initial to final study (p less than 0.05). Patients with occluded infarct-related arteries (n = 5) exhibited no significant recovery of cyclic variation (0.3 +/- 0.3-0.6 +/- 0.3 dB). A blinded analysis of standard two-dimensional echocardiographic images revealed no significant recovery of wall thickening in either group over the same time intervals. Ultrasonic tissue characterization promptly detects acute myocardial infarction and may delineate potential beneficial effects of coronary artery reperfusion manifest by restoration of cyclic variation of integrated backscatter in the presence of severe wall motion abnormalities.

Ultrasound integrated backscatter tissue characterization of remote myocardial infarction in human subjects.

To determine whether quantitative ultrasound tissue characterization differentiates normal myocardial regions from segments of remote infarction, 32 consecutive patients with a diagnosis of previous myocardial infarction were evaluated. Images were obtained in real time with a modified two-dimensional ultrasound system capable of providing continuous signals in proportion to the logarithm of integrated backscatter along each A line. In 15 patients, adequate parasternal long-axis images that delineated both normal and infarct segments were obtained with standard time-gain compensation. Image data were analyzed to yield both magnitude and delay (electrocardiographic R wave to nadir normalized for the QT interval) of the cyclic variation of backscatter. Cyclic variation was present in 55 of 56 normal myocardial sites, averaging (mean +/- SEM) 3.2 +/- 0.2 dB in magnitude and exhibiting a mean normalized delay of 0.87 +/- 0.03. The magnitude of cyclic variation in infarct segments was significantly reduced to 1.1 +/- 0.2 dB (42 sites), and the delay was markedly increased to 1.47 +/- 0.12 (21 sites) (p less than 0.0001 for both). In 20 of 42 infarct sites, no cyclic variation was detectable. Thus, ultrasound tissue characterization quantitatively differentiated infarct segments from normal myocardium in patients with remote myocardial infarction.

Hemodynamic monitoring and pacing with one catheter: a pilot study.

Attempts to incorporate the monitoring of central pressures and pacing into one catheter have heretofore been unsuccessful. Recently, a new catheter for monitoring central hemodynamic pressures, which has a right ventricular port (Chandler pacing port), has been devised, which has been reported to allow for simultaneous acquisition of hemodynamic data and reliable pacemaker function as well. To assess the reliability of this catheter, we studied ten consecutive Swan-Ganz catheterizations utilizing this new catheter system. In all instances, hemodynamic monitoring was established without difficulty. In three instances, because of right heart enlargement, fluoroscopy was necessary to position the pacing probe at the right ventricular apex. In all ten instances, a threshold of less than 2.5 mV was obtained. Isolated PVCs and nonsustained ventricular tachycardia were common during insertion. After initial placement, the threshold for sensing and pacing was assessed every 6 hr. Malfunction occurred in three patients. In all, repositioning was accomplished without marked difficulty; in one it required fluoroscopy. In three instances, the Swan-Ganz pacing catheter system malfunctioned. These data are similar to data utilizing other modalities of temporary pacing and suggest that this catheter may be capable of providing hemodynamic monitoring and pacing from a single percutaneous procedure.