Exercise echocardiography predicts development of left ventricular dysfunction in medically and surgically treated patients with asymptomatic severe aortic regurgitation.

OBJECTIVE: To assess resting and exercise echocardiography for prediction of left ventricular dysfunction in patients with significant asymptomatic aortic regurgitation. DESIGN: Cohort study of patients with aortic regurgitation. SETTING: Tertiary referral centre specialising in valvar surgery. PATIENTS: 61 patients (38 men, 23 women; mean (SD) age 53 (14) years) with asymptomatic or minimally symptomatic aortic regurgitation and no known coronary artery disease; 35 were treated medically and 26 had aortic valve replacement. INTERVENTIONS: Exercise echocardiography was used to evaluate ejection fraction, which was measured on the resting and post-stress images using the modified Simpson method. Patients with an increment of ejection fraction after exercise were denoted as having contractile reserve (CR+); those without an increment were labelled CR-. MAIN OUTCOME MEASURES: Standard univariate and multivariate methods and receiver operating characteristic analyses were used to assess the ability of contractile reserve to predict follow up ejection fraction. RESULTS: In the 35 medically treated patients, 13 of 21 (62%) with CR+ (mean (SD) ejection fraction increment 7 (3)%) had preserved ejection fraction on follow up. In the 14 patients with CR- (ejection fraction decrement 8 (4)%), 13 (93%) had a decrement of ejection fraction on follow up from 60 (5)% at baseline to 54 (3)% on follow up (p = 0.005). Age, resting left ventricular dimensions, medical treatment, aortic regurgitation severity, exercise capacity, and rate-pressure product were similar in both CR+ and CR- groups. Among the 26 surgical patients, 13 showed CR+ (ejection fraction increase 9 (5)%), all of whom had an increase in ejection fraction on follow up (from 49% to 59%). Of 13 surgical patients with CR- (ejection fraction decrease 7 (5)%), 10 (77%) showed the same or worse ejection fraction on postoperative follow up. CONCLUSIONS: Contractile reserve on exercise echocardiography is a better predictor of left ventricular decompensation than resting indices in asymptomatic patients with aortic regurgitation. In patients undergoing aortic valve replacement, contractile reserve had a better correlation with resting ejection fraction on postoperative follow up. Measurement of contractile reserve may be useful to monitor the early development of myocardial dysfunction in asymptomatic patients with aortic regurgitation, and may help to optimise the timing of surgery.

Color coding of digitized echocardiograms: description of a new technique and application in detecting and correcting for cardiac translation.

Color coding is a new software application for digitized echocardiograms that displays a reference image of end diastole throughout the cardiac cycle. With color-coded digitized echocardiograms, we determined the frequency of, and corrected for cardiac translation in 21 bicycle stress echocardiograms in patients who were known to be without significant coronary artery disease or wall motion abnormalities. Translation was present in 4%, 40%, and 74% of rest, postexercise, and peak exercise images, respectively, and was noted most frequently in the apical views, 59% of four-chamber views and 40% of two-chamber views. Interobserver and intraobserver agreement for detection of translation was 81% and 86%, respectively. Translation was corrected by shifting digitized images to eliminate transverse displacement of the mitral valve anulus and restore normal basal-to-apical shortening. Ventricular contraction was assessed as normal in 92% of the images in which correction for translation was performed. In the remaining images, poor image quality (3%) and apparent wall motion abnormalities (5%) prevented the studies from being graded as normal. We conclude that color coding of digitized echocardiograms is a useful new technique that can be applied to detect and correct for cardiac translation.

Receptors for C3b on the neutrophil surface associate with the cytoskeleton-containing cell residue subsequent to cell lysis with non-ionic detergent. Cytoskeletal-CR1 interactions.

Radioiodinated Fab' and F(ab')2 fragments were prepared from 57F monoclonal antibody which is specific for the C3b receptor (CR1) on human cells. We find that both Fab' and F(ab')2 fragments bind to CR1 on human neutrophils and then dissociate, at 0 degree C, with half-lives of 172 and 35 min, respectively. In addition to binding to cell surface CR1, both antibody fragments bind specifically to the isolated non-ionic detergent-insoluble cellular residue (NDIR) which remains after cell lysis and solubilization in Triton X-100. We also find that Fab' and F(ab')2 antibody fragments remain associated with the NDIR after the radiolabeled antibody fragments are allowed to bind to cell surface CR1, the unbound fragments removed, and the cells subsequently lysed in non-ionic detergent. Because the cytoskeletal matrix (together with the cell nucleus) makes up a substantial portion of the NDIR, these results suggest that some fraction of cell surface CR1 may be associated in vivo with the cytoskeletal matrix. However, post-lysis association of cell surface-CR1-antibody fragment complexes to the NDIR occurs. Examination of the binding kinetics of this interaction reveals that less than 10% of cell surface CR1 exists bound to the NDIR prior to cell lysis. While the nature of post-cell lysis association of CR1 with the NDIR is unknown, several modulating effects are noted. For example, binding of bivalent cross-linking agents to CR1 on cells followed by a 37 degrees C incubation is known to induce internalization of cell surface CR1. We find that binding of F(ab')2 antibody fragments under these conditions causes a 50% decrease in association of this 57F fragment to the NDIR. Pretreatment of the cells at 37 degrees C with the chemotactic peptide N-formyl-methionyl-leucylphenylalanine similarly caused a 50% decrease of (Fab'-labeled) CR1 association with the NDIR cell fraction. These results support the hypothesis that chemotactic peptide serves to enhance CR1-mediated adherence to C3b-bearing targets by increasing the density of CR1 on the cell surface rather than by inducing cytoskeletal-dependent, detergent-stable, CR1 redistribution on the cell surface.