PurposeProgression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such ‘vulnerable periods’.ParticipantsBIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor.Methods and analysisWe hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate ‘vulnerable periods’ during which patients with CAD are at high short-term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for non-fatal ACS had occurred in 50 patients. A case–cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS.Future plans and disseminationFollow-up and event adjudication have been completed. Prespecified biomarker analyses are currently being performed and dissemination through peer-reviewed publications and conference presentations is expected from the third quarter of 2016. Should identification of a ‘vulnerable period’ prove to be feasible, then future research could focus on event reduction through pharmacological or mechanical intervention during such periods of high risk for ACS.Trial registration numberNTR1698 and NTR1106.

This study was designed (1) to assess the relationship between stress exercise echocardiography (echo) and 201-Tl single photon emission computed tomography (SPECT) applied simultaneously in 23 patients who were candidates to percutaneous transluminal coronary angioplasty (PTCA), (2) to assess the relationship between the development of exercise-induced wall motion abnormalities, transient perfusion defects and the severity of quantitatively assessed coronary stenoses and (3) to compare the functional improvement after PTCA by exercise echo and SPECT. Before PTCA there was an agreement of 78% between stress echo (new wall motion abnormalities) and SPECT (transient perfusion defects) results. All patients with a percentage diameter stenosis greater than 70% had a positive echo and SPECT, while they were both negative if the percentage diameter stenosis was less than 50%. In 19 patients re-studied 4 weeks after PTCA, an ischaemic response at stress echo was found in two of the 13 patients who had a positive stress echo test before PTCA, and SPECT was still positive in three of the 10 patients who had a positive SPECT study before PTCA. Echo and SPECT were concordant in 17/19 cases. It is concluded that exercise echo and 201-Tl SPECT are useful non-invasive tools for the functional assessment of patients before and after PTCA, and that they provide highly concordant results.

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Uptake of thallium 201 (201Tl) in the lungs has been proposed as a measure of left ventricular dysfunction with exercise. To study this hypothesis, we compared the lung/-heart (LH) ratio assessed from anterior planar images (ANT-P), from anterior images obtained during single photon emission tomography (SPET) acquisition (ANT-T) and from short-axis tomographic cross-sections (CS) in early post-exercise thallium 201 scintigrams. The study population consisted of 54 prepercutaneous transluminal coronary angioplasty (PTCA) studies (82% with single-vessel disease), 50 post-PTCA studies, 33 pre-coronary artery bypass surgery (CABG) studies (71% with three-vessel disease), 30 post-CABG studies and 30 patients with a left ventricular dysfunction (LVD) due to an acute myocardial infarction; 18 individuals with a low likelihood of coronary artery disease (CAD) served as a control group. The results demonstrated that, on average, the LH ratios obtained from ANT-P and ANT-T were not significantly different for all study groups; these ratios increased significantly with ischaemia and with LVD relative to non-ischaemic situations. However, the LH ratios in CS did not show a relation with ischaemia nor with LVD and differed significantly from the LH-ratios assessed from the anterior approaches. Each of the three approaches (ANT-P, ANT-T, CS) was characterized by large overlaps of LH ratios for the different study groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Uptake of thallium (Tl)-201 in the lungs has been proposed as a measure of left ventricular dysfunction. In this study we were interested in pursuing two goals: 1) to assess possible relationships between the post-exercise Tl-201 lung-heart (LH)-ratio determined from the anterior view during SPECT-acquisition, myocardial ischemia and the extent of coronary artery disease; and 2) to explore the effects of coronary revascularisation procedures on the LH-ratio. The study group consisted of 145 patients with early and late postexercise Tl-201 tomograms, including 32 PTCA-patients with pre- and post-PTCA studies and 20 patients who underwent coronary artery bypass surgery (CABG) with corresponding pre- and post-CABG studies. Ischemia was defined as evoked angina during the exercise test in combination with greater than or equal to 1 mm horizontal or downsloping ST-depression on the ECG. The severity of coronary obstructions was assessed from coronary angiograms with a PC-based digital caliper technique; a stenosis was defined to be significant when its severity exceeded 50% diameter stenosis. The LH-ratio was defined by the ratio of the mean pulmonary counts and the mean myocardial counts assessed from corresponding regions of interest (ROI's) positioned over the left lung and the heart, respectively in the anterior view of a tomographic data acquisition procedure. Our results made clear that the LH-ratio was not significantly different between patients with and without ischemia during exercise, and between patients with single vs. multiple vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)