The Use of Embolic Signal Detection in Multicenter Trials to Evaluate Antiplatelet Efficacy

Abstract

Background and Purpose-The CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotidStenosis) trial proved the effectiveness of the combination of clopidogrel and aspirin compared with aspirin alone in reducing presence and number of microembolic signals (MES) in patients with recently symptomatic carotid stenosis. The present study aimed at installing primary and secondary quality control measures in CARESS because MES evaluation relies on subjective judgment by human experts. Methods-As primary quality control, centers participating in CARESS evaluated a reference digital audio tape (DAT) before the study containing both MES and artifacts. Interobserver agreement of classifying signals as MES was expressed as proportions of specific agreement of positive ratings (psϮvalues). For all DATs included in CARESS (nϭ300), online number of MES and off-line number of MES read by the central reader were compared using correlation coefficients. As secondary control, a sample of 16 of 300 DATs was cross-validated by another independent reader (post-trial validator). Results-For the reference tape, the cumulative psϮvalue was 0.894 based on 12 of 14 observers. Two observers with very different results improved after a training procedure. Agreement between post-trial validator and central reader was psϩϭ0.805, indicating very good agreement. Correlation between online evaluation and off-line evaluation of DATs was very good overall (cumulative ϭ0.84; PϽ0.001). Conclusion-Multicenter studies using MES as outcome parameter are feasible. However, primary and secondary quality control procedures are important.

Impact of Clinical Environment on Embolus Detection: A Comparison of Automated and Manual Detection of Doppler Embolic Signals

“…There was positive agreement between all 3 panel members for 83% of signals. This is reasonable agreement considering the low intensities of these signals [3]. The observed intensity distribution was typical of that published previously for post-carotid-endarterectomy data [14] and is shown in figure 1.…”

“…The poor reliability in the detection of weak embolic signals by human experts is widely acknowledged and has been the subject of numerous studies [1,2,3,4]. However, these studies were exclusively conducted using off-line analysis of pre-recorded data.…”

“…In a previous study, we found that the detection of some weak (<14 dB) embolic signals was severely inhibited by the fundamental limitations of the human auditory system [1]. Psychoacoustics limitations are likely to be exacerbated by noise and observer fatigue in the operating theatre or recovery room; however, previous studies have exclusively investigated interobserver agreement under ideal conditions [1,2,3,4,5]. …”

Techniques for Optimizing Results in Carotid Stenting

“…Clopidogrel, an oral thienopyridine of the same family as ticlopidine but better tolerated, irreversively inhibits a chemoreceptor on platelet membranes, thus impairing adhesion. Dual therapy with clopidogrel and ASA has been able to demonstrate reduction in silent microemboli detected by TCD among patients with recent symptomatic carotid stenosis [31].…”

Innovative Approaches to Assess the Impact and Steps to Decrease the Neurological Consequences of Ablation

“…Importantly, this has led to the development of criteria by different consensus committees to bring uniformity to these measurements. 80,81 Dittrich et al 82 showed that standardized MES readings by TCD can be used as a robust and a surrogate marker in clinical trials as long as independent quality control mechanisms are in place. Intracardiac echocardiography.…”