Woo-Hyun Lim

Biodegradable-polymer drug-eluting stents vs. bare metal stents vs. durable-polymer drug-eluting stents: a systematic review and Bayesian approach network meta-analysis

BACKGROUNDnThe aim of this study was to compare the safety and efficacy of biodegradable-polymer (BP) drug-eluting stents (DES), bare metal stents (BMS), and durable-polymer DES in patients undergoing coronary revascularization, we performed a systematic review and network meta-analysis using a Bayesian framework.nnnMETHODS AND RESULTSnStudy stents included BMS, paclitaxel-eluting (PES), sirolimus-eluting (SES), endeavor zotarolimus-eluting (ZES-E), cobalt-chromium everolimus-eluting (CoCr-EES), platinium-chromium everolimus-eluting (PtCr-EES), resolute zotarolimus-eluting (ZES-R), and BP biolimus-eluting stents (BP-BES). After a systematic electronic search, 113 trials with 90 584 patients were selected. The principal endpoint was definite or probable stent thrombosis (ST) defined according to the Academic Research Consortium within 1 year.nnnRESULTSnBiodegradable polymer-biolimus-eluting stents [OR, 0.56; 95% credible interval (CrI), 0.33-0.90], SES (OR, 0.53; 95% CrI, 0.38-0.73), CoCr-EES (OR, 0.34; 95% CrI, 0.23-0.52), and PtCr-EES (OR, 0.31; 95% CrI, 0.10-0.90) were all superior to BMS in terms of definite or probable ST within 1 year. Cobalt-chromium everolimus-eluting stents demonstrated the lowest risk of ST of all stents at all times after stent implantation. Biodegradable polymer-biolimus-eluting stents was associated with a higher risk of definite or probable ST than CoCr-EES (OR, 1.72; 95% CrI, 1.04-2.98). All DES reduced the need for repeat revascularization, and all but PES reduced the risk of myocardial infarction compared with BMS.nnnCONCLUSIONSnAll DESs but PES and ZES-E were superior to BMS in terms of ST within 1 year. Cobalt-chromium everolimus-eluting stents was safer than any DES even including BP-BES. Our results suggest that not only the biodegradability of polymer, but the optimal combination of stent alloy, design, strut thickness, polymer, and drug all combined determine the safety of DES.

Safety and efficacy of everolimus-versus sirolimus-eluting stents: a systematic review and meta-analysis of 11 randomized trials

BACKGROUNDnWhile EES have proven superior to paclitaxel-eluting stents, it remains uncertain whether EES improve clinical outcomes compared to SES, which are the most efficacious among the first-generation drug-eluting stents. We performed a meta-analysis of randomized trials comparing the efficacy and safety of everolimus-eluting stents (EES) versus sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary intervention.nnnMETHODSnFrom online and offline search until December 2011, we identified 11 randomized trials (total 12,869 patients). The primary endpoint was major adverse cardiac events.nnnRESULTSnThe risk of major adverse cardiac events did not differ significantly between the patients treated with EES versus SES [OR, 0.90 (95% CI, 0.77-1.04); P = .162]. However, we found a significant reduction in the risk of repeat revascularization in the EES arm [OR, 0.85 (95% CI, 0.71-1.00); P = .047]. There were no significant differences regarding the risk of cardiac death [OR, 0.97 (95% CI, 0.74-1.27); P = .834], or myocardial infarction [OR, 0.95 (95% CI, 0.75-1.20), P = .656]. The risk of definite or probable stent thrombosis tended to be lower [OR, 0.68 (95% CI, 0.45-1.02); P = .065], while definite ST was significantly lower [OR, 0.44 (95% CI, 0.25-0.80); P = .007] with EES.nnnCONCLUSIONSnIn a large systematic overview of comparative trials involving percutaneous revascularization with drug-eluting stents, treatment with EES significantly reduced the risk of repeat revascularization and definite ST compared to SES. We found no significant differences in the risk of cardiac death or myocardial infarction.

Comparison of endothelialization and neointimal formation with stents coated with antibodies against CD34 and vascular endothelial-cadherin.

Vascular endothelial-cadherin (VE-cadherin) is exclusively expressed on the late endothelial progenitor cells (EPC). Therefore, VE-cadherin could be an ideal target surface molecule to capture circulating late EPC. In the present study, we evaluated whether anti-VE-cadherin antibody-coated stents (VE-cad stents) might accelerate endothelial recovery and reduce neointimal formation more than anti-CD34 antibody-coated stents (CD34 stents) through the superior ability to capture the late EPC. The stainless steel stents were coated with anti-human VE-cadherin antibodies or anti-human CD34 antibodies under the same condition. In vitro, VE-cad stents showed higher number of adhering EPC (823.6 ± 182.2 versus 379.2 ± 137.2 cells per HPF, p < 0.001). VE-cad stents also demonstrated better specific capturing of cells with endothelial lineage markers than CD34 stents did in flow cytometric analysis. VE-cad stents showed more effective re-endothelialization after 1 h, 24 h, and 3 days in vivo. At 42 days, VE-cad stents demonstrated significantly smaller neointima area (0.92 ± 0.38 versus 1.24 ± 0.41 mm(2), p = 0.002) and significantly lower PCNA positive cells in neointima (1684.8 ± 658.8/mm(2) versus 2681.7 ± 375.1/mm(2), p = 0.008), compared with CD34 stents. In conclusion, VE-cad stents captured EPC and endothelial cells more selectively in vitro, accelerated re-endothelialization over stents, and reduced neointimal formation in vivo, compared with CD34 stents.

Stent Coated With Antibody Against Vascular Endothelial-Cadherin Captures Endothelial Progenitor Cells, Accelerates Re-Endothelialization, and Reduces Neointimal Formation

Objective—In contrast to CD34, vascular endothelial-cadherin (VE-cadherin) is exclusively expressed on the late endothelial progenitor cells (EPC) whereas not on the early or myeloid EPC. Thus, VE-cadherin could be an ideal target surface molecule to capture circulating late EPC. In the present study, we evaluated whether anti-VE–cadherin antibody-coated stents (VE-cad stents) might accelerate endothelial recovery and reduce neointimal formation through the ability of capturing EPC. Methods and Results—The stainless steel stents were coated with rabbit polyclonal anti-human VE-cadherin antibodies and exposed to EPC for 30 minutes in vitro. The number of EPC that adhered to the surface of VE-cad stents was significantly higher than bare metal stents (BMS) in vitro, which was obliterated by pretreatment of VE-cad stent with soluble VE-cadherin proteins. We deployed VE-cad stents and BMS in the rabbit right and left iliac arteries, respectively. At 48 hours after stent deployment in vivo, CD-31–positive endothelial cells adhered to VE-cad stent significantly more than to BMS. At 3 days, scanning electron microscopy showed that over 90% surface of VE-cad stents was covered with endothelial cells, which was significantly different from BMS. At 42 days, neointimal area that was filled with smooth muscle cells positive for actin or calponin was significantly smaller in VE-cad stents than in BMS by histological analysis (0.95±0.22 versus 1.34±0.43 mm2, respectively, P=0.02). Immuno-histochemical analysis revealed that infiltration of inflammatory cells was not significantly different between 2 stents. Conclusion—VE-cad stents captured EPC successfully in vitro, accelerated endothelial recovery on stent, and eventually reduced neointimal formation in vivo.

Underweight is a risk factor for atrial fibrillation: A nationwide population-based study

BACKGROUNDnObesity is a well-known risk factor for development of atrial fibrillation (AF). However, the impact of underweight on AF has not been previously recognized. We sought to determine the risk of AF in subjects with underweight in this study.nnnMETHODSnWe analyzed clinical data from a total of 132,063 individuals with the age of 40years or older who received health care checkups arranged by the national insurance program between 2003 and 2004. Newly diagnosed nonvalvular AF was identified using claim data during a median follow-up duration of 9.0years.nnnRESULTSnThe mean body mass index (BMI) of patients was 23.9kg/m(2), and 3,323 individuals (2.5%) were classified as being underweight (BMI <18.5kg/m(2)). During the study period, 3,237 individuals (2.5%) developed AF. There was a U-shaped relationship between BMI and AF occurrence: Each 1.0kg/m(2) increase of BMI above 20kg/m(2) was associated with a 6% increased risk of AF (p<0.001), while each 1.0kg/m(2) lower BMI below 20kg/m(2) was associated with a 13% increased risk of AF (p<0.001) after multivariable adjustment. Underweight was significantly associated with 23% increased risk of AF, while obesity classes I and II were with 26% and 120% increased risk of AF, respectively. Excess risk of AF in the underweight was independent of thyroid disease, chronic lung disease, or history of malignancy, and was not attributable to cigarette smoking, low socioeconomic status, excessive physical activity, or heavy alcohol consumption.nnnCONCLUSIONnBMI has a U-shaped relationship with the risk of AF. Underweight was an independent risk factor for AF independent of confounding factors such as chronic lung disease and malignancy. These findings suggest that underweight is associated with biological effects that contribute to the development of AF.

Variability of fractional flow reserve according to the methods of hyperemia induction.

We performed this study to evaluate the variability of fractional flow reserve (FFR) values which were measured from various methods of hyperemia induction.

Fabrication of biofunctional stents with endothelial progenitor cell specificity for vascular re-endothelialization.

Endothelial progenitor cells (EPCs) have been identified as a crucial factor for re-endothelialization after stenting, resulting in the prevention of stent thrombosis and neointimal hyperplasia. Because EPCs can be introduced by antibody-antigen interactions, the suitable choice of antibody and the biocompatible surface modification technology including antibody immobilization are essential for developing an EPC-capturing stent. In this study, we fabricated a biofunctional stent with EPC specificity by grafting a hydrophilic polymer and consecutively immobilizing the antibody against vascular endothelial cadherin (VE-cadherin) which is one of the specific EPC surface markers. The surface of a stainless steel stent was sequentially modified by acid-treatment, silanization and covalent attachment of polymers not only to improve biocompatibility but also to introduce functional groups on the stent surface. The surface-modified stent immobilized anti-VE-cadherin antibodies, and the EPCs were remarkably captured whereas THP-1s, human acute monocytic leukemia cells, were not adsorbed on the stent. Furthermore, we confirmed that the recruited EPCs developed the endothelial cell layers on the antibody-conjugated stent. These positive in vitro results will encourage the extensive application of biofunctional surface modification technology for a variety of medical devices.

Evaluation of the association between diabetic retinopathy and the incidence of atrial fibrillation: A nationwide population-based study.

BACKGROUNDnAtrial fibrillation (AF) is prevalent among type 2 diabetic patients. However, the association between diabetic retinopathy (DR) and AF is controversial.nnnMETHODSnWe included 40,500 patients with type 2 diabetes (≥40years, mean age 62±11years, 53% men) without AF from the Korean National Insurance Service-National Sample Cohort (2002-2007). Subjects were classified without DR (non-DR, n=30,178), with DR (DR, n=8920), and with proliferative DR (PDR, n=1402).nnnRESULTSnDuring a mean 5.9-year follow-up, 1261 (3.1%) patients were newly diagnosed as having AF (4.9, 6.0, and 8.3 per 1000 person-years in the non-DR, DR, and PDR groups, respectively). In multivariate Cox proportional hazard models, patients in the DR and PDR groups had a significantly higher risk of AF than those in the non-DR group (DR group: hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.00-1.30; PDR group: HR 1.46, 95% CI 1.13-1.87); p for trend <0.001). The risk of AF increased in patients with DR and end-stage renal disease (ESRD) (HR 2.39, 95% CI 1.31-3.96, p<0.001) and in those with PDR and ESRD (HR 3.59, 95% CI 1.96-5.97, p<0.001) compared to those without DR and ESRD.nnnCONCLUSIONSnThe presence and severity of DR was significantly associated with the incidence of AF. Also, the presence of ESRD had an impact on the incidence of AF in patients with DR.

Ambient air pollution and out-of-hospital cardiac arrest

BACKGROUNDnSudden cardiac arrest is a leading cause of cardiovascular death. This study aimed at investigating the impact of short-term exposure to air pollutants on the incidence of OHCA.nnnMETHODSnWe identified OHCA cases that occurred in Seoul between 2006 and 2013 from the nationwide emergency medical service database. The association of the daily incidence of OHCA with air pollutants including PM2.5 (particles ≤ 2.5 μm in aerodynamic diameter), PM10, CO, O3, NO2, and SO2 was analyzed with the use of time-series and case-crossover analyses.nnnRESULTSnA total of 21,509 OHCAs of presumed cardiac origin were identified. An elevation in PM2.5 by 10 μg/m(3) at a moving average of lag 1 and 2 days was shown to increase the risk of OHCA by 1.30% (95% confidence intervals, 0.20-2.41%). An exposure-response relationship was present: the risk of OHCA increased significantly with even a mild elevation of PM2.5 (10-15 μg/m(3)) and further increased with higher levels. While PM10, NO2, CO, and SO2 also showed significant associations with OHCA in single-pollutant models, only PM2.5 remained significant after adjustment for other pollutants. Subgroup analyses showed male sex, advanced age, hypertension, diabetes, heart disease, and history of stroke were risk factors for OHCA in response to elevations in PM2.5.nnnCONCLUSIONSnThis study showed that increased ambient levels of PM2.5 were significantly associated with increased risk of OHCA within 1 to 2 days of exposure, which had a dose-response relationship. Subjects with conventional cardiovascular risk factors were more susceptible to harm of PM2.5.

Delayed Diagnosis of Traumatic Ventricular Septal Defect in Penetrating Chest Injury: Small Evidence on Echocardiography Makes Big Difference

Cardiac trauma from penetrating chest injury is a life-threatening condition. It was reported that < 10% of patients arrives at the emergency department alive. Penetrating chest injury can cause serious damage in more than 1 cardiac structure, including myocardial lacerations, ventricular septal defect (VSD), fistula between aorta and right cardiac chamber and valves. The presence of pericardial effusion (even a small amount) on the initial echocardiography might be the only clue to serious cardiac damage in the absence of definite evidence of anatomical defect in heart. We here present a case, in which clear diagnosis of VSD and pseudoaneurysmal formation was delayed a few days after penetrating chest injury due to the lack of anatomical evidence of damage.