Coronary Responses and Differential Mechanisms of Late Stent Thrombosis Attributed to First-Generation Sirolimus- and Paclitaxel-Eluting Stents

ObjectivesThe purpose of this study was to assess the mechanism(s) of late stent thrombosis (LST) and vascular healing responses in first-generation polymeric drug-eluting stents (DES).BackgroundRecent clinical trials have reported variations in late lumen loss between first-generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). Little is known, however, about the vascular responses, time course of healing, and underlying mechanism(s) of complications of LST between platforms in human coronary implants.MethodsThe overall analysis included 174 cases (230 DES lesions) from the CVPath Institute's stent registry. Histomorphometry was performed on coronary stents from 127 patients (171 lesions) who died ≥30 days after receiving stent implants in which fibrin deposition, endothelial strut coverage, inflammatory response, and mechanism(s) of in-stent thrombosis were assessed.ResultsBoth platforms demonstrated increased neointimal thickness over time where values were greater in PES (mean 0.13 mm; range 0.03 to 0.20 mm) than SES (mean 0.10 mm; range 0.04 to 0.15 mm; p = 0.04). The percentage of uncovered struts was similar between SES and PES including stents with LST (SES = 21% vs. PES = 27%; p = 0.47). The underlying mechanism(s) of LST, however, was strikingly different between platforms; localized strut hypersensitivity was exclusive to SES, whereas malapposition secondary to excessive fibrin deposition was the underlying cause in PES. Moreover, although both PES and SES showed nearly complete strut coverage after 12 months for on-label use, the majority of stents placed for off-label indications remained unhealed after 12 months in both types of DES.ConclusionsDifferential mechanisms of LST involving either hypersensitivity or excessive fibrin were identified between first-generation DES in which overall stent healing was further delayed in DES placed for off-label indications

Incidence and Predictors of Drug-Eluting Stent Fracture in Human Coronary Artery A Pathologic Analysis

ObjectivesThe aim of this study was to perform pathologic assessment on stent fracture.BackgroundClinically, stent fracture has been reported in 1% to 2% of patients after drug-eluting stent (DES) implantation.MethodsHigh-contrast film-based radiographs of 177 consecutive lesions from the CVPath DES autopsy registry were reviewed. Stent fracture was graded as I (single-strut fracture), II (≥2 struts), III (≥2 struts with deformation), IV (with transection without gap), and V (with transection causing gap in stent segment). The incidence of adverse pathologic findings (thrombosis and restenosis) was assessed histologically.ResultsStent fracture was documented in 51 lesions (29%; grade I = 10, II = 14, III = 12, IV = 6, and V = 9). Lesions with stent fracture had longer duration after implantation (172 days [interquartile range (IQR) 31 to 630 days] vs. 44 days [IQR 7 to 270 days], p = 0.004), a higher rate of Cypher (Cordis Corp., Miami Lakes, Florida) stent usage (63% vs. 36%, p = 0.001), longer stent length (30.0 mm [IQR 22.0 to 40.0 mm] vs. 20.0 mm [IQR 14.0 to 27.3 mm], p < 0.0001), and a higher rate of overlapping stents (45% vs. 22%, p = 0.003). Although fracture with grade I to IV did not have significant impact on the occurrence of adverse pathologic findings such as thrombosis and restenosis, 67% of the grade V fracture lesions were associated with adverse pathologic findings at fracture sites. Longer stent length, use of Cypher, and longer duration of implant were identified as independent risk factors of stent fracture by logistic regression analysis.ConclusionsThe incidence of stent fracture was 29% lesions at autopsy, which is much higher than clinically reported. A high rate of adverse pathologic findings was observed in lesions with grade V stent fracture, whereas fracture with grade I to IV did not have a significant impact on the pathological outcome

The Pathology of Neoatherosclerosis in Human Coronary Implants Bare-Metal and Drug-Eluting Stents

ObjectivesHuman coronary bare-metal stents (BMS) and drug-eluting stents (DES) from autopsy cases with implant duration >30 days were examined for the presence of neointimal atherosclerotic disease.BackgroundNeointimal atherosclerotic change (neoatherosclerosis) after BMS implantation is rarely reported and usually occurs beyond 5 years. The incidence of neoatherosclerosis after DES implantation has not been reported.MethodsAll available cases from the CVPath stent registry (n = 299 autopsies), which includes a total of 406 lesions—197 BMS, 209 DES (103 sirolimus-eluting stents [SES] and 106 paclitaxel-eluting stents [PES])—with implant duration >30 days were examined. Neoatherosclerosis was recognized as clusters of lipid-laden foamy macrophages within the neointima with or without necrotic core formation.ResultsThe incidence of neoatherosclerosis was significantly greater in DES lesions (31%) than BMS lesions (16%; p < 0.001). The median stent duration with neoatherosclerosis was shorter in DES than BMS (DES, 420 days [interquartile range [IQR]: 361 to 683 days]; BMS, 2,160 days [IQR: 1,800 to 2,880 days], p < 0.001). Unstable lesions characterized as thin-cap fibroatheromas or plaque rupture were more frequent in BMS (n = 7, 4%) than in DES (n = 3, 1%; p = 0.17), with relatively shorter implant durations for DES (1.5 ± 0.4 years) compared to BMS (6.1 ± 1.5 years). Independent determinants of neoatherosclerosis identified by multiple logistic regression included younger age (p < 0.001), longer implant durations (p < 0.001), SES usage (p < 0.001), PES usage (p = 0.001), and underlying unstable plaques (p = 0.004).ConclusionsNeoatherosclerosis is a frequent finding in DES and occurs earlier than in BMS. Unstable features of neoatherosclerosis are identified for both BMS and DES with shorter implant durations for the latter. The development of neoatherosclerosis may be yet another rare contributing factor to late thrombotic events

Impact of transport pathways on the time from symptom onset of ST-segment elevation myocardial infarction to door of coronary intervention facility

AbstractBackgroundReducing total ischemic time is important in achieving better outcome in ST-segment elevation myocardial infarction (STEMI). Although the onset-to-door (OTD) time accounts for a large portion of the total ischemic time, factors affecting prolongation of the OTD time are not established.PurposeThe purpose of this study was to determine the impact of transport pathways on OTD time in patients with STEMI.Methods and subjectsWe retrospectively studied 416 STEMI patients who were divided into 4 groups according to their transport pathways; Group 1 (n=41): self-transportation to percutaneous coronary intervention (PCI) facility; Group 2 (n=215): emergency medical service (EMS) transportation to PCI facility; Group 3 (n=103): self-transportation to non-PCI facility; and Group 4 (n=57): EMS transportation to non-PCI facility. OTD time was compared among the 4 groups.Essential resultsMedian OTD time for all groups combined was 113 (63–228.8)min [Group 1, 145 (70–256.5); Group 2, 71 (49–108); Group 3, 260 (142–433); and Group 4, 184 (130–256)min]. OTD time for EMS users (Groups 2 and 4) was 138min shorter than non-EMS users (Groups 1 and 3). Inter-hospital transportation (Groups 3 and 4) prolonged OTD by a median of 132min compared with direct transportation to PCI facility (Groups 1 and 2). Older age, history of myocardial infarction, prior PCI, shock at onset, high Killip classification, and high GRACE Risk Score were significantly more frequent in EMS users.Principal conclusionsSelf-transportation without EMS and inter-hospital transportation were significant factors causing prolongation of the OTD time. Approximately 35% of STEMI patients did not use EMS and 21% of patients were transported to non-PCI facilities even though they called EMS. Awareness in the community as well as among medical professionals to reduce total ischemic time of STEMI is necessary; this involves educating the general public and EMS crews

Correlation of Optic Nerve Microcirculation with Papillomacular Bundle Structure in Treatment Naive Normal Tension Glaucoma

Purpose. To assess the association between optic nerve head (ONH) microcirculation, central papillomacular bundle (CPB) structure, and visual function in eyes with treatment naive normal tension glaucoma (NTG). Methods. This study included 40 eyes of 40 patients with NTG and 20 eyes of 20 normal patients. We used laser speckle flowgraphy (LSFG) to measure mean blur rate (MBR) in all eyes and calculated the ratio of MBR in the horizontal quadrants of tissue area ONH (temporal/nasal ratio of MBR in the tissue area: T/N MT). Clinical findings also included retinal nerve fiber layer thickness (RNFLT) and ganglion cell complex thickness (GCCT) in the CPB and macular areas, best-corrected visual acuity (BCVA), mean deviation (MD), and refractive error. Results. T/N MT was correlated with both BCVA and MD. The OCT parameters most highly correlated with T/N MT were macular RNFLT and mid-CPB RNFLT. Furthermore, T/N MT, mid-CPB RNFLT, and macular RNFLT were higher in NTG than in normal eyes. A discrimination analysis revealed that T/N MT and refractive error were independent factors indicating NTG. Conclusions. Our results suggest that T/N MT is a candidate biomarker of NTG. Furthermore, T/N MT reflects visual function, including acuity and sensitivity, and CPB structure