Tomohiko Teramoto

Morphological differences of tissue characteristics between early, late, and very late restenosis lesions after first generation drug-eluting stent implantation: an optical coherence tomography study

AIMS Restenosis of drug-eluting stents (DESs) might be different from that of bare metal stent restenosis in diverse ways including mechanisms and time course; however, these have not been fully examined. To gain insight into the mechanisms and time course of DES restenosis, we evaluated the characteristics of restenotic lesions of first generation DES using optical coherence tomography (OCT). METHODS AND RESULTS We compared the morphological characteristics of early in-stent restenosis (<1 year: E-ISR, n = 43), late ISR (1-3 years: L-ISR, n = 22), and very late ISR (>3 years: VL-ISR, n = 21). OCT qualitative restenotic tissue analysis included the assessment of tissue structure [homogeneous or four types of heterogeneous intima (thin-cap fibroatheroma (TCFA)-like, layered, patchy or speckled pattern)], the presence of the peri-strut low intensity area (PLIA), microvessels, disruption with cavity, and intraluminal material and was performed at every 1 mm slice of the entire stent length. In addition to a greater trend for heterogeneous intima at the later phase, TCFA-like pattern image, intra-intima microvessels were increased from the early to the very late phase. On the other hand, the speckled pattern image was decreased from the early to the very late phase. CONCLUSION The OCT morphological characteristics of DES restenotic tissue varied at different time-points. OCT images in early DES ISR might be associated with delayed arterial healing, and neoatherosclerosis might contribute to late catch-up phenomenon (L-ISR and VL-ISR) after DES implantation.

Initial Success Rate of Percutaneous Coronary Intervention for Chronic Total Occlusion in a Native Coronary Artery Is Decreased in Patients Who Underwent Previous Coronary Artery Bypass Graft Surgery

OBJECTIVES This study sought to compare the initial success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) in a native coronary artery (NCA) in patients with and without previous coronary artery bypass grafting (CABG) and to assess predictive factors. BACKGROUND Landmark novel wiring techniques for CTO-PCI have contributed to improvement in the initial success of CTO-PCI. However, challenges persist in CTO-PCI in NCA in pCABG patients. METHODS Patients who underwent CTO-PCI in an NCA were selected and classified into 2 groups: pCABG (206 PCIs in 153 patients) and nCABG (1,431 PCIs in 1,139 patients). RESULTS CTO was located more often in the left anterior descending artery (p = 0.0003), and severe calcified lesions were observed more frequently in the pCABG group (p < 0.0001). Although the retrograde attempt was tried more frequently in the pCABG group, the CTO-PCI success rate was significantly lower in the pCABG patients than in the nCABG patients (71% vs. 83%). Longer procedural time and greater radiation exposure were needed in the pCABG patients. Logistic regression analysis among the pCABG patients revealed that intravascular ultrasound use and parallel wiring were positive factors, and lesion tortuosity was a negative factor. CONCLUSIONS The initial success rate of CTO-PCI of an NCA in the pCABG group was significantly decreased compared with that in the nCABG group. Anatomic complexity and unstable hemodynamic state were unfavorable conditions. This study reveals that the issues to be overcome are lying with CTO revascularization in an NCA in pCABG patients.

Evaluation of the peri-strut low intensity area following sirolimus- and paclitaxel-eluting stents implantation: Insights from an optical coherence tomography study in humans ☆

BACKGROUND Recent pathological studies have demonstrated that peri-strut low intensity area (PLIA) seen on optical coherence tomography (OCT) imaging represents the presence of fibrinogen and/or extracellular matrix. We sought to assess the clinical prevalence of PLIA and its relation to neointimal proliferation after the implantation of sirolimus- (SES) and paclitaxel-eluting stents (PES) in humans. METHODS Seventy patients underwent 6-months follow-up OCT after SES (43 stents) or PES (37 stents) implantation. PLIA was defined as a region around stent struts with homogenous lower intensity than surrounding tissue on OCT images without signal attenuation. The incidence of stent struts with PLIA (+PLIA struts) was calculated as the number of +PLIA struts/number of all struts (%). RESULTS PES showed a higher incidence of stents with PLIA than SES (86% vs. 58%; p=0.005) with a higher prevalence of +PLIA struts (27.8±21.9% vs. 10.9±11.0%; p=0.0008). SES with PLIA showed a significantly greater neointimal thickness (NIT) than SES without PLIA (p=0.02), while PES showed a similar tendency (p=0.19). In a detailed strut basis analysis, average NIT on +PLIA struts were significantly greater than that on -PLIA struts in both SES and PES. In addition, average NIT was positively correlated with the prevalence of +PLIA struts (SES: Rho=0.73; p<0.0001, PES: Rho=0.58, p=0.0005) in both stents. CONCLUSIONS The prevalence of PLIA was significantly higher in PES than in SES. The presence and extent of PLIA might be associated with intimal thickening after 1st-generation DES implantation.

Impact on Optical Coherence Tomographic Coronary Findings of Fluvastatin Alone Versus Fluvastatin + Ezetimibe

Although lipid-lowering therapy with statin and ezetimibe has been reported to provide greater reduction in low-density lipoprotein cholesterol levels than statin monotherapy, the effect of supplemental therapy on plaque stabilization is yet to be fully elucidated. Cap thickness of fibroatheroma evaluated by optical coherence tomography (OCT) is a major determinant of vulnerable plaque. The primary objective of this study is to evaluate the effect of ezetimibe in addition to fluvastatin on the progression of coronary atherosclerotic plaque evaluated by OCT. Sixty-three patients with angina pectoris with intermediate, nonculprit, lipid-rich plaque lesions evaluated by OCT were enrolled. The patients were divided into 2 groups: ezetimibe (10 mg/day) + fluvastatin (30 mg/day), and fluvastatin (30 mg/day) alone, and serial OCT examinations were performed at baseline and 9-month follow-up. A total of 57 patients (ezetimibe + fluvastatin, n = 31; fluvastatin alone, n = 26) underwent serial OCT examinations. The change in low-density lipoprotein cholesterol level was significantly larger in the ezetimibe + fluvastatin group compared with fluvastatin-alone group (-34.0 ± 32.0 vs -8.3 ± 17.4 mg/dl, p <0.001). Fibrous cap thickness was significantly increased and the angle of the lipid plaque was significantly decreased in both groups. The change in the fibrous cap thickness was significantly greater in the ezetimibe + fluvastatin group (0.08 ± 0.08 mm vs 0.04 ± 0.06 mm, p <0.001). In conclusion, lipid-lowering therapy by ezetimibe + fluvastatin could increase the fibrous cap thickness of lipid-rich plaque compared with fluvastatin monotherapy.

Dual Manganese-Enhanced and Delayed Gadolinium-Enhanced MRI Detects Myocardial Border Zone Injury in a Pig Ischemia- Reperfusion Model

Background— Gadolinium (Gd)-based delayed-enhancement MRI (DEMRI) identifies nonviable myocardium but is nonspecific and may overestimate nonviable territory. Manganese (Mn2+)-enhanced MRI (MEMRI) denotes specific Mn2+ uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI identifies viable infarct border zone (BZ) myocardium in vivo. Methods and Results— Sixty-minute left anterior descending coronary artery IR injury was induced in 13 adult swine. Twenty-one days post-IR, 3-T cardiac MRI was performed. MEMRI was obtained after injection of 0.7 mL/kg Mn2+ contrast agent. DEMRI was then acquired after injection of 0.2 mmol/kg Gd. Left ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI defect from DEMRI signal identified injured BZ myocardium. Explanted hearts were analyzed by 2,3,5-triphenyltetrazolium chloride stain and tissue electron microscopy to compare infarct, BZ, and remote myocardium. Average LV ejection fraction was reduced (30±7%). MEMRI and DEMRI infarct volumes correlated with 2,3,5-triphenyltetrazolium chloride stain analysis (MEMRI, r=0.78; DEMRI, r=0.75; P<0.004). MEMRI infarct volume percentage was significantly lower than that of DEMRI (14±4% versus 23±4%; P<0.05). BZ MEMRI signal-to-noise ratio (SNR) was intermediate to remote and core infarct SNR (7.5±2.8 versus 13.2±3.4 and 2.9±1.6; P<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and core infarct SNR (8.4±5.4 versus 3.3±0.6 and 14.3±6.6; P>0.05). Tissue electron microscopy analysis exhibited preserved cell structure in BZ cardiomyocytes despite transmural DEMRI enhancement. Conclusions— The dual-contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This approach may identify injured, at-risk myocardium in ischemic cardiomyopathy.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction.

Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part II. In Vivo Imaging of Bone Marrow Stromal Cells in Swine with PET/CT and MR Imaging

Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone. Clinical MR imaging and PET reporter gene molecular imaging were performed after intravenous injection of the radiotracer fluorine 18-radiolabeled 9-[4-fluoro-3-(hydroxyl methyl) butyl] guanine ((18)F-FHBG). Linear regression analysis of both MR imaging and PET data and nonlinear regression analysis of PET data were performed, accounting for multiple injections per animal. Results MR imaging showed a positive correlation between MSC-TF-NP cell number and dephasing (dark) signal (R(2) = 0.72, P = .0001) and a lower detection limit of at least approximately 1.5 × 10(7) cells. PET reporter gene imaging demonstrated a significant positive correlation between MSC-TF and target-to-background ratio with the linear model (R(2) = 0.88, P = .0001, root mean square error = 0.523) and the nonlinear model (R(2) = 0.99, P = .0001, root mean square error = 0.273) and a lower detection limit of 2.5 × 10(8) cells. Conclusion The authors quantitatively determined the limit of detection of MSC after CCT in swine by using clinical PET reporter gene imaging and clinical MR imaging with cell prelabeling. (©) RSNA, 2016 Online supplemental material is available for this article.

Acute stent recoil and optimal balloon inflation strategy: an experimental study using real-time optical coherence tomography.

AIMS Our aim was to evaluate stent expansion and acute recoil at deployment and post-dilatation, and the impact of post-dilatation strategies on final stent dimensions. METHODS AND RESULTS Optical coherence tomography (OCT) was performed on eight bare metal platforms of drug-eluting stents (3.0 mm diameter, n=6 for each) during and after balloon inflation in a silicone mock vessel. After nominal-pressure deployment, a single long (30 sec) vs. multiple short (10 sec x3) post-dilatations were performed using a non-compliant balloon (3.25 mm, 20 atm). Stent areas during deployment with original delivery systems were smaller in stainless steel stents than in cobalt-chromium and platinum-chromium stents (p<0.001), whereas subsequent acute recoil was comparable among the three materials. At post-dilatation, acute recoil was greater in cobalt-chromium and platinum-chromium stents than in stainless steel stents (p<0.001), resulting in smaller final stent areas in cobalt-chromium and platinum-chromium stents than in stainless steel stents (p<0.001). In comparison between conventional and latest-generation cobalt-chromium stents, stent areas were not significantly different after both deployment and post-dilatation. With multiple short post-dilatations, acute recoil was significantly improved from first to third short inflation (p<0.001), achieving larger final area than a single long inflation, despite stent materials/designs (p<0.001). CONCLUSIONS Real-time OCT revealed significant acute recoil in all stent types. Both stent materials/designs and post-dilatation strategies showed a significant impact on final stent expansion.

The Achievability of Minimum Contrast Procedures for the Prevention ofContrast Induced Nephropathy in Patients with Chronic Kidney Disease: AProspective, Multicentre Trial

Background The practical utility of minimum contrast procedures in a real world setting is unclear. In this trial, the reality of this strategy was investigated. Methods Patients with an estimated glomerular filtration rate (eGFR) of <=45 ml/min/1.73m2 were included in this study with dates ranging from Jan 17th 2012 to Oct 8th 2013. Various methods to minimize the amount of contrast media were applied. An achievement rate of contrast volume/eGFR<2.0 was calculated and the characteristics of the patients and catheter procedures were investigated. Results A total of 88 patients were enrolled. There were 34 patients who underwent a diagnostic coronary angiogram (CAG group) and 54 patients who underwent an interventional procedure (PCI group). The PCI group tended to use a larger amount of contrast media compared to the CAG group (39 ± 49 ml vs 25 ± 14 ml, p=0.06). A ratio of contrast volume to eGFR of less than 2.0 was achieved in 100% of the CAG group but in only 82% of the PCI group. The patients with complex procedures (complex PCI) such as use of a rotablator and treatment of chronic total occlusion used significantly more contrast media than patients with other procedures (simple PCI). (87 ± 69 ml vs 23 ± 27 ml, p=0.006) Surprisingly, when simple PCI group was compared to the CAG group, there was no difference in the contrast volume used. (23 ± 27 vs 25 ± 14 ml, p=0.708) Conclusions Simple PCI can be done as safely as in CAG patients with chronic kidney dysfunction. Complex PCI should be done with careful assessment of the balance between risk and benefit.

PRIOR CORONARY ARTERY BYPASS GRAFTING DIMINISH THE INITIAL SUCCESS RATE OF PERCUTANEOUS CORONARY INTERVENTION TO THE CHRONIC TOTAL OCCLUSION IN THE NATIVE CORONARY ARTERY

Background: The epoch-making techniques for percutaneous coronary intervention (PCI) of the chronic total occlusions (CTO) such as retrograde approach and CART technique have contributed to the improvement of initial success of PCI to the CTO lesions, however, we are still forced to do complex procedures to recanalize the CTO lesions in the native coronary artery (NCA) in the prior coronary artery bypass grafting (CABG) patients. Thus, the purpose of this study is to compare the initial success rate of CTO lesions in NCA between the prior CABG patients and without CABG patients, and to speculate the affecting factors.