Coronary magnetic resonance imaging after routine implantation of bioresorbable vascular scaffolds allows non-invasive evaluation of vascular patency

<div><p>Background</p><p>Evaluation of recurrent angina after percutaneous coronary interventions is challenging. Since bioresorbable vascular scaffolds (BVS) cause no artefacts in magnetic resonance imaging (MRI) due to their polylactate-based backbone, evaluation of vascular patency by MRI might allow for non-invasive assessment and triage of patients with suspected BVS failure.</p><p>Methods</p><p>Patients with polylactate-based ABSORB-BVS in proximal coronary segments were examined with 3 Tesla MRI directly (baseline) and one year after implantation. For assessment of coronary patency, a high-resolution 3D spoiled gradient echo pulse sequence with fat-saturation, T2-preparation (TE: 40 ms), respiratory and end-diastolic cardiac gating, and a spatial resolution of (1.08 mm)³ was positioned parallel to the course of the vessel for bright blood imaging. In addition, a 3D navigator-gated T2-weighted variable flip angle turbo spin echo (TSE) sequence with dual-inversion recovery black-blood preparation and elliptical k-space coverage was applied with a voxel size of (1.14 mm)³. For quantitative evaluation lumen diameters of the scaffolded areas were measured in reformatted bright and black blood MR angiography data.</p><p>Results</p><p>11 patients with implantation of 16 BVS in the proximal coronary segments were included, of which none suffered from major adverse cardiac events during the one year follow up. Vascular patency in all segments implanted with BVS could be reliably assessed by MRI at baseline and after one year, whereas segments with metal stents could not be evaluated due to artefacts. Luminal diameter within the BVS remained constant during the one year period. One patient with atypical angina after BVS implantation was noninvasively evaluated showing a patent vessel, also confirmed by coronary angiography.</p><p>Conclusions</p><p>Coronary MRI allows contrast-agent free and non-invasive assessment of vascular patency after ABSORB-BVS implantation. This approach might be supportive in the triage and improvement of diagnostic workflows in patients with postinterventional angina and scaffold implantation.</p><p>Trial registration</p><p>German Register of Clinical Studies <a target="_blank">DRKS00007456</a></p></div

CB₂ receptor deficiency does not influence atherosclerosis in mice.

<p>A and B, CB₂^+/+/LDLR^−/− (N = 13) and CB₂^−/−/LDLR^−/− (N = 12) mice consumed HCD for 16 weeks and underwent analysis of intimal lesion area in the aortic root (A) and arch (B). Pooled data ± SEM are shown on the left; representative images stained for lipid deposition (Oil-red-O) are displayed below the corresponding graph. C, The abdominal aortas of mice treated as described above underwent <i>en face</i> analysis of the lipid deposition. Oil-red-O-positive staining in relation to total wall area was quantified and is dispayed as pooled data ± SEM (N = 13 and 12); representative images are shown below. D, Sections of aortic roots of mice treated as described above were analyzed for lipid-, macrophage-, collagen-, T cell-, smooth muscle cell- and apoptotic cell content. Oil-red-O-, Mac-3-, picosirius red-, CD4-, α-actin- and TUNEL-positive staining in relation to total wall area is described as mean ± SEM (N = 13 and 12). Asterisks indicate a significant change, defined as p<0,05.</p

Characteristics of study animals before and after feeding.

<p>Characteristics of study animals before and after feeding.</p

Inflammatory cell recruitment is differentially affected by CB₂ receptor stimulation.

<p>A, Wild-type mice received intraperitoneal injections of 4% thioglycollate after pre-treatment with JWH-133 or vehicle control. Leukocyte recruitment into the peritoneal cavity was quantified after 72 and 4 h. Data represent mean ± SEM. Asterisks indicate significant change, defined as p<0,05. B, In parallel, thioglycollate-elicited accumulation of leukocytes in the peritoneal cavity was quantified in CB₂^−/−/LDLR^−/− mice and CB₂^+/+/LDLR^−/− control animals. Data for both 72 and 4 h stimulation are expressed as mean ± SEM. C, PMA-activated thioglycollate-elicited peritoneal leukocytes obtained from wild-type (Bl6) mice were allowed to adhere on TNFα-activated endothelial cells (EC) isolated by magnetic bead separation from wild-type mice in the presence or absence of 40 µM JWH-133. Adhering leukocytes were quantified under microscope after the indicated time points in the flow chamber (N = 3 each). In parallel experiments PMA-activated thioglycollate-elicited peritoneal leukocytes from CB₂^−/−/LDLR^−/− mice were allowed to adhere on TNFα-activated EC isolated from CB₂^−/−/LDLR^−/− mice. Adhesion was quantified and compared with the interaction of peritoneal leukocytes and EC isolated from CB₂^+/+/LDLR^−/− (N = 5 each). Pooled data represent mean ± SEM.</p

Viability and ICAM-1 expression on murine endothelial cells is unaffected by CB₂ receptor signaling.

<p>A, Murine EC isolated from LDLR^−/− mice were stimulated with or without TNFα (20 ng/ml) and JWH-133 (4 µM and 40 µM, N = 4). In parallel, experiments, EC isolated from CB₂^−/−/LDLR^−/− mice and CB₂^+/+/LDLR^−/− control animals were stimulated with or without TNFα (20 ng/ml, N = 6). Cell lysates were analyzed for ICAM-1 by Western blotting. Western blots were analyzed densitometrically and adjusted for GAP-DH. Pooled data are given as mean ± SEM and representative blots are shown. B, Similarly, Murine EC isolated from wild-type mice where stimulated with indicated concentrations of JWH-133 and with or without TNFα (20 ng/ml). The cells were then analyzed for ICAM-1 expression using flow cytometric assays. Data is shown as mean ± SEM (N = 6). Asterisks indicate significant change, defined as p<0,05. C, In supernatants of EC treated as described above MCP-1 was quantified by ELISA. Data is shown as mean ± SEM. D and E, Murine EC isolated from wild-type mice were stimulated with indicated concentrations of JWH-133 and then the rate of apoptosis was determined using the Apo-ONE® Assay (D). Data is shown as the mean ± SEM (N = 5). The supernatant of cells treated in a similar manner were used to examine cytotoxicity with the CytoTox-ONE™ Assay (E). Data is shown as the percent of control (N = 6).</p

Pharmacokinetics of JWH-133 using mass spectrometry.

<p>Mice were subjected to intraperitoneal injection of JWH-133 (5 mg/kg body weight) on day 1, 3, 6, 8, and 10. On day ten, the serum levels of JWH-133 were determined at the indicated time points using mass spectrometry. The concentration of JWH-133 is given as the mean ± SEM (N = 6).</p

Baseline and procedural characteristics.

<p>Baseline and procedural characteristics.</p

Multiple BVS implantation in the left anterior descending artery (LAD).

<p>Left: result in the coronary angiogram with 3 proximal and overlapping scaffolds. One drug eluting stent (SYNERGY 2.5/20mm) was implanted distally, since BVS was not deliverable to this area. MRI at baseline shows open scaffolds in 3D FLASH and 3D TSE, while the distal DES causes significant artefacts not allowing for judgement of vessel patency. Especially the black blood 3D TSE sequences confirm open scaffolds at baseline and after one year in this symptom-free patient.</p

1-year follow up data.

<p>1-year follow up data.</p

Treatment with the CB₂ agonist JWH-133 does not modulate atherosclerosis in mice.

<p>A and B, LDLR^−/− mice consuming high cholesterol diet for 16 weeks (HCD) received intraperitoneal injections of 5 mg/kg JWH-133 (N = 10) or vehicle control (Tocris, N = 8) three times a week. Intimal lesion area in the aortic root (A) and arch (B) are diplayed as pooled data ± SEM; representative images stained for lipid deposition (Oil-red-O) are shown below the corresponding graph. C, The abdominal aortas of mice treated as described above underwent <i>en face</i> analysis of lipid deposition. Oil-red-O-positive staining in relation to total wall area was quantified and is displayed as pooled data ± SEM (N = 8 and 10); representative images are shown below. D, Sections of aortic roots of mice treated as described above were analyzed for lipid-, macrophage-, collagen-, T cell-, smooth muscle cell- and apoptotic cell content. Oil-red-O-, Mac-3-, picosirius red-, CD4-, α-actin- and TUNEL-positive staining in relation to total wall area is given as mean ± SEM (N = 8 and 10).</p