Comparison of neointimal coverage and extra-stent lumen between sirolimus and everolimus-eluting stent using optical coherence tomography.

The external lumen of a stent [defined as extra-stent lumen (ESL)] assessed by optical coherence tomography (OCT) may be related to the risk of thrombus formation after sirolimus-eluting stent (SES) implantation. An everolimus-eluting stent (EES) might provide relatively minimal inflammatory reaction and appropriate neointimal coverage. The purpose of this study was to compare the neointimal thickness and ESL between SES and EES. Patients who underwent OCT examination more than 7 months after either SES or EES implantation were enrolled. Stent area (SA), lumen area (LA), neointimal area (NIA) and neointimal thickness (NIT) of each strut were measured at 1-mm intervals between stented segments. The area, angle (summation per cross-section) and depth (maximum distance from adjacent vessel surface to the outline of stent) of ESL were analyzed. A total of 49 lesions were included (SES n = 20, EES n = 29). Mean follow-up period was 11 months. A total of 998 cross-sections and 9874 struts were analyzed. There were no differences in stent area, lumen area and neointimal area (SA: 6.01 ± 1.60 vs. 6.02 ± 1.40 mm(2), p = 0.572, LA: 5.37 ± 1.52 vs. 5.29 ± 1.34 mm(2), p = 0.692, NIA: 0.64 ± 0.49 vs. 0.72 ± 0.37 mm(2), p = 0.493). Mean NIT of SES and EES were 0.11 ± 0.05 and 0.10 ± 0.05 mm, respectively (p = 0.367). Conversely, area, angle and depth of ESL in SES group were significantly greater than those in EES group (0.20 ± 0.39 vs. 0.03 ± 0.09 mm(2), p < 0.001, 56.2 ± 59.1° vs. 20.1 ± 41.9°, p < 0.001, 0.10 ± 0.09 vs. 0.03 ± 0.03 mm, p < 0.001). OCT showed that the efficacy of neointimal growth suppression is similar between SES and EES, whereas the adverse vascular response after EES implantation is smaller than that after SES implantation.

Rapid electrical stimulation causes alterations in cardiac intercellular junction proteins of cardiomyocytes.

The intercellular junctions contain two complexes, adhesion junctions (AJ) and connexin (Cx) gap junctions (GJs). GJs provide the pathway for intercellular current flow. AJs mediate normal mechanical coupling and play an important role in the stability of GJs. We investigated the effects of rapid electrical stimulation (RES) on cardiac intercellular junctions, especially ß-catenin and Cx43 alterations. We also studied the effects of ANG II receptor blockade on intercellular junction remodeling. Neonatal rats were euthanized by decapitation, and cardiomyocytes were prepared, cultured, and subjected to RES. We used real-time PCR, western blot analysis, and immunohistochemical methods. Conduction properties were examined by an extracellular potential mapping system. Cx43 protein expression in cardiomyocytes was significantly increased after 60 min. ß-Catenin expression in the total cell fraction was significantly increased after 30 min. The expression level of ß-catenin in the nucleus, which functions as a T cell factor/lymphocyte enhancer binding factor transcriptional activator of Cx43 with its degradation regulated by glycogen synthase kinase-3ß, was dramatically increased after 10 min. Conduction velocity was increased significantly by RES for 60 min. Olmesartan prevented most these effects of RES. We showed an increase of phosphorylated glycogen synthase kinase-3ß, which is phosphorylated by activated MAPKs and inhibits ß-catenin degradation, was attenuated by olmesartan. The changes in ß-catenin precede Cx43 GJ remodeling and might play an important role in the formation and stability of GJs. Olmesartan might be a new upstream arrhythmia therapy by modulating intercellular junction remodeling through the ß-catenin signaling pathway.

Serial changes in the three-dimensional aspect of the side-branch ostium jailed by a drug-eluting stent assessed by optical coherence tomography.

The present study investigated serial changes in the three-dimensional (3D) aspect of the jailed side-branch (SB) ostium. We evaluated 32 patients who underwent examination with optical coherence tomography (OCT) both at baseline and at follow-up. After reconstruction of the 3D images, we classified the configuration of overhanging struts at the SB orifice into three groups according to the 3D aspect of the jailing configuration. The number of compartments divided by the stent strut was counted. The side-branch flow area (SBFA), i.e., the area of the SB ostium except for jailing struts, was measured by cut-plane analysis. Forty-eight SBs of 25 patients were analyzed. Thirteen SBs were classified as the No-jail type (N-type), 19 as the Simple-jail type (S-type; no longitudinal link at the carina), and 16 as the Complex-jail type (C-type; had a link at the carina). In the N-type, the SBFA was significantly increased at follow-up (P = 0.018). In the C-type, the SBFA was significantly decreased at follow-up (P = 0.002). Percent reduction of SBFA in the C-type group was significantly greater than that in the N-type or S-type groups (S-type vs. C-type P = 0.002, N-type vs. C-type P < 0.001). 3D-OCT images showed that some of the compartments were filled with tissue. The number of compartments was significantly decreased at follow-up (P < 0.001). In the C-type group, the SBFA was significantly decreased and small compartments were filled with tissue. These findings suggest that stent jail complexity is associated with the progression of SB ostial stenosis.

Serial three-dimensional optical coherence tomography assessment of strut coverage and intraluminal structures after drug-eluting stent implantation.

Understanding of intraluminal structure and distribution of uncovered struts after drug-eluting stent implantation are limited by only 2-dimensional (2D) optical coherence tomography (OCT) images. We compared tissue coverage with 3-dimensional (3D) OCT and 2D quantitative analyses, and changes in intraluminal structure immediately after (baseline) everolimus-eluting stent (EES) implantation and at follow-up. The 2D analyses of uncovered struts ratio and tissue coverage thickness at a 0.5-mm interval were compared to 3D-OCT images and visually classified for the degree of tissue coverage. The difference in tissue coverage at baseline and follow-up after EES implantation was evaluated with tissue coverage scores (TCS) calculated by the 3D-OCT classification (Grade 0-3). 3D-OCT classifications were negatively correlated with uncovered-to-total struts (r = -0.864, P < 0.001) and positively correlated with tissue coverage thickness (r = 0.905, P < 0.001). Follow-up TCS was greater than baseline TCS (0.2 ± 0.4 vs. 1.4 ± 0.5, P < 0.001). Moreover, changes in intraluminal structures and longitudinal distribution of uncovered struts were assessed. Incomplete stent appositions, in-stent dissections, and thrombi were decreased at follow-up, indicating progressive arterial healing. The distribution of uncovered-to-total struts could be assessed by 3D-OCT, which was related to 2D analysis. Significant correlations between 3D-OCT classifications and quantitative analyses were shown. The classification and visual assessment of intraluminal structures by 3D-OCT were useful in evaluating arterial healing after EES implantation.

Alterations in adhesion junction precede gap junction remodelling during the development of heart failure in cardiomyopathic hamsters.

AIMS: The intercalated disc (ID) contains two complexes, the adhesion junction (AJ) and the gap junction (GJ). We studied ID remodelling and its potential role in arrhythmogenesis and investigated the effects of olmesartan on ID remodelling during development of heart failure (HF) in UM-X7.1 cardiomyopathic hamsters. METHODS AND RESULTS: The UM-X7.1 hamsters showed left ventricular (LV) hypertrophy by the age of 10-15 weeks and a moderate impairment in LV contractility at 20 weeks. At age 10-15 weeks, 10-20% of the hamsters died suddenly without HF, and ventricular tachycardia (VT)/ventricular fibrillation (VF) was induced in ∼30% of hamsters. Electron microscopy showed that density linking cell-to-cell adhesion was irregular and unclearly defined, and filamentous structures attached to electron-dense components were arranged in disorder. Western blotting showed that the total cellular expression level of ß-catenin was decreased, and expression of nuclear ß-catenin, which functions as a T-cell factor/lymphocyte enhancer binding factor transcriptional activator, was also remarkably decreased. At age 20 weeks, LV connexin43 expression showed a remarkable decrease, and the VT/VF induction rate was ∼90%. In UM-X7.1 hamsters, olmesartan improved abnormal ID ultrastructural changes, attenuated the decrease of total cellular and nuclear ß-catenin expression, decreased VT/VF induction, and improved survival rate. CONCLUSION: These results suggest that changes in AJ protein precede connexin43 GJ alterations, and ID remodelling might contribute to arrhythmogenesis during the development of HF. Angiotensin receptor blockade might be a new therapy for lethal ventricular arrhythmia by modulating both AJ and GJ remodelling.