Erratum: Two-year clinical outcomes in stable angina and acute coronary syndrome after percutaneous coronary intervention of left main coronary artery disease.

[This corrects the article on p. 1084 in vol. 31, PMID: 27756119.].

Effect of Stents Coated with Artemisinin or Dihydroartemisinin in a Porcine Coronary Restenosis Model.

BACKGROUND AND OBJECTIVES: Artemisinin and dihydroartemisinin are drugs used to treat malaria. These drugs suppress inflammatory reactions. The aim of this study was to examine the anti-intima hyperplasia effect of a novel drug-eluting stent with artemisinin or dihydroartemisinin in a porcine coronary restenosis model. MATERIALS AND METHODS: Pigs were randomized into four groups; in the first, the coronary arteries (20 pigs, a total of 40 coronary arteries, with 10 coronary arteries in each group) was implanted with bare metal stents (BMS, n=10); the second group was given polymer-coated stents (PCS, n=10); the third group was treated with artemisinin-eluting stents (AES, n=10); and the fourth group was given dihydroartemisinin-eluting stents (DAES, n=10). Histopathologic analysis was performed 28 days after stenting. RESULTS: The injury and fibrin scores among the four groups were not significantly different. However, the internal elastic lamina, lumen area, and neointima area were significantly different. Moreover, the percent area of stenosis (46.2±18.66% in BMS vs. 89.4±10.92% in PCS vs. 83.3±17.07% in AES vs. 36.7±11.20% in DAES, p<0.0001) and inflammation score (1.0 [range: 1.0-1.0] vs. 3.0 [range: 2.25-3.0] vs. 3.0 [range: 1.0-3.0] vs. 2.0 [range: 1.75-3.0] in BMS, PCS, AES, and DAES, respectively; p<0.001) were markedly decreased in the DAES group compared to the PCS group. CONCLUSION: DES, which uses a natural substance, dihydroartemisinin, showed a neointima and inflammatory suppressive effect in a porcine coronary restenosis model.

Two-year clinical outcomes in stable angina and acute coronary syndrome after percutaneous coronary intervention of left main coronary artery disease.

BACKGROUND/AIMS: This study appraised the long term clinical outcomes of patients treated with percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease. There are limited data regarding long-term clinical outcomes after PCI for ULMCA disease. METHODS: From 2001 to 2011, a total of 448 patients who underwent PCI for ULMCA disease and had 2-year clinical follow-up, were analyzed. The study patients were divided into two groups: group I (stable angina pectoris [SAP], n = 60, 48 men, 62 ± 10 years) and group II (acute coronary syndrome [ACS], n = 388, 291 men, 64 ± 10 years). We evaluated clinical and angiographic characteristics and major adverse cardiac events (MACE) during 2-year clinical follow-up. RESULTS: Mean age of studied patients was 64 ± 10 years with 339 male patients. Average stent diameter was 3.6 ± 0.4 mm and stent length was 19.7 ± 6.3 mm. Stent implantation techniques and use of intravascular ultrasound guidance were not different between two groups. In-hospital mortality was 0% in group I and 7% in group II (p = 0.035). One-month mortality was 0% in group I and 7.7% in group II (p = 0.968). Two-year survival rate was 93% in the group I and 88.4% in the group II (p = 0.921). Predictive factors for 2-year MACE were hypertension, Killip class ≥ 3, and use of intra-aortic balloon pump by multivariate analysis. CONCLUSIONS: Although in-hospital mortality rate was higher in ACS than in SAP, clinical outcomes during 2-year clinical follow-up were similar between SAP and ACS after PCI of ULMCA.

A novel polymer-free drug-eluting stent coated with everolimus using nitrogen-doped titanium dioxide film deposition in a porcine coronary restenosis model.

BACKGROUND: Titanium dioxide (TiO2) films have superior biocompatibility and may be effective as drug-binding matrices for drug-eluting stents (DESs). We sought to evaluate efficacy of a polymer-free DES coated with everolimus using nitrogen-doped TiO2 film deposition in a porcine coronary restenosis model. METHODS: Forty coronary arteries in 20 pigs were randomly allocated to group 1 (bare-metal stents (BMSs), 3.0×18mm, n=10), group 2 (BMSs with nitrogen-doped TiO2 film deposition, 3.0×18mm, n=10), group 3 [commercial everolimus-eluting stent, 3.0×18mm, n=10], and group 4 (polymer-free everolimus-eluting stent using nitrogen-doped TiO2 film deposition, 3.0×18mm, n=10). Stents were randomly implanted in the left anterior descending coronary artery and left circumflex artery with stent:artery ratio of 1.3. Four weeks later, pigs underwent follow-up coronary angiography and were sacrificed for histopathologic analysis. RESULTS: Percent area stenosis was greater in group 1 compared to groups 3 and 4 (46.4±13.8% vs. 30.2±11.7% vs. 29.2±8.9%, respectively, p=0.005). Fibrin score was lower in groups 1 and 2, compared to groups 3 and 4: 0.87±0.67 vs. 0.76±0.61 vs. 2.27±0.24 vs. 1.75±0.31, respectively, p<0.001). Injury score and inflammation score were not different. Comparison between DES showed a higher fibrin score in group 3 than group 4 (2.27±0.24 vs. 1.75±0.31, p=0.023). CONCLUSIONS: In a porcine model of coronary restenosis, a novel polymer-free DES using nitrogen-doped TiO2 film deposition shows higher biocompatibility and compares favorably with a commercial DES.

Effects of combination therapy of statin and N-acetylcysteine for the prevention of contrast-induced nephropathy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Acute myocardial infarction (AMI) is a risk factor for contrast-induced nephropathy (CIN). We investigated whether pretreatment with statin, N-acetylcysteine (NAC) and sodium bicarbonate (NaHCO3) reduces the risk of CIN. METHODS: We conducted a prospective trial and enrolled a total of 334 ST-segment elevation myocardial infarction (STEMI) patients. Patients were divided into four groups: Group I (statin 40mg), Group II (statin 80mg), Group III (statin 80mg plus NAC 1200mg) and Group IV (regimen of group III plus NaHCO3 154mEq/L). CIN was defined as ≥25% or ≥0.5mg/dL increase in serum creatinine from the baseline within the 72h after PCI. RESULTS: CIN occurred in 72 (21.6%) patients. The incidence of CIN was the lowest in the group III (14.3%), and multivariate analysis showed the lower incidence of CIN in group III compared to Group I [odds ratio (OR) 0.29, 95% confidence interval (CI) 0.13-0.64, p=0.002]. Admission hyperglycemia [(AHG)>198mg/dL] (OR 2.20, 95% Cl 1.20-3.68, p=0.011) and the use of intra-aortic balloon pump (IABP) (OR 4.20, 95% CI 1.38-12.78, p=0.016) were independent predictors for CIN. The CIN (OR 9.00, 95% CI 1.30-62.06, p=0.026) was an independent predictor for in-hospital mortality. CONCLUSIONS: Combination of high-dose statin plus NAC was associated with lower incidence of CIN in patients with STEMI who underwent primary PCI compared to statin only.

Effect of stents coated with a combination of sirolimus and alpha-lipoic acid in a porcine coronary restenosis model.

The aim of this study was to evaluate antiproliferative sirolimus- and antioxidative alpha-lipoic acid (ALA)-eluting stents using biodegradable polymer [poly-L-lactic acid (PLA)] in a porcine coronary overstretch restenosis model. Forty coronary arteries of 20 pigs were randomized into four groups in which the coronary arteries had a bare metal stent (BMS, n = 10), ALA-eluting stent with PLA (AES, n = 10), sirolimus-eluting stent with PLA (SES, n = 10), or sirolimus- and ALA-eluting stent with PLA (SAS, n = 10). A histopathological analysis was performed 28 days after the stenting. The ALA and sirolimus released slowly over 30 days. There were no significant differences between groups in the injury or inflammation score; however, there were significant differences in the percent area of stenosis (56.2 ± 11.78% in BMS vs. 51.5 ± 12.20% in AES vs. 34.7 ± 7.23% in SES vs. 28.7 ± 7.30% in SAS, P < 0.0001) and fibrin score [1.0 (range 1.0-1.0) in BMS vs. 1.0 (range 1.0-1.0) in AES vs. 2.0 (range 2.0-2.0) in SES vs. 2.0 (range 2.0-2.0) in SAS, P < 0.0001] between the four groups. The percent area of stenosis based on micro-computed tomography corresponded with the restenosis rates based on histopathological stenosis in different proportions in the four groups (54.8 ± 7.88% in BMS vs. 50.4 ± 14.87% in AES vs. 34.5 ± 7.22% in SES vs. 28.9 ± 7.22% in SAS, P < 0.05). SAS showed a better neointimal inhibitory effect than BMS, AES, and SES at 1 month after stenting in a porcine coronary restenosis model. Therefore, SAS with PLA can be a useful drug combination for coronary stent coating to suppress neointimal hyperplasia.

Reliable femoral chronic total occlusion model using a thin biodegradable polymer coated copper stent in a porcine model.

Chronic total occlusions (CTOs) are common in patients with peripheral arterial disease (PAD). This study aimed to examine the feasibility and reliability of a CTO induced by a thin biodegradable polymer (polyglycolic acid) coated copper stent in a porcine femoral artery. Novel thin biodegradable polymer coated copper stents (9 mm long) were crimped on an angioplasty balloon (4.5 mm diameter × 12 mm length) and inserted into the femoral artery. Histopathologic analysis was performed 35 days after stenting. In five of six stented femoral arteries, severe in-stent restenosis and total occlusion with collateral circulation were observed without adverse effects such as acute stent thrombosis, leg necrosis, or death at 5 weeks. Fibrous tissue deposition, small vascular channels, calcification, and inflammatory cells were observed in hematoxylin-eosin, Carstair's, and von Kossa tissue stains; these characteristics were similar to pathological findings associated with CTOs in humans. The neointima volume measured by micro-computed tomography was 93.9 ± 4.04 % in the stented femoral arteries. CTOs were reliably induced by novel thin biodegradable polymer coated copper stents in porcine femoral arteries. Successful induction of CTOs may provide a practical understanding of their formation and application of an interventional device for CTO treatment.

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker, in a porcine model of acute myocardial infarction.

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.

Comparison of zotarolimus- and everolimus-eluting stents in patients with ST-elevation myocardial infarction and chronic kidney disease undergoing primary percutaneous coronary intervention.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor outcomes after percutaneous coronary intervention (PCI). The aim of the study was to compare zotarolimus- and everolimus-eluting stents used during primary PCI in patients with acute myocardial infarction (AMI) and CKD. METHODS: We selected 854 consecutive ST-elevation MI patients with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2)) undergoing primary PCI who were followed up for 12 months. They were divided into two groups based on type of stents implanted: (1) zotarolimus-eluting stent (ZES) and (2) everolimus-eluting stent (EES). The study end point was the 12-month major adverse cardiac events (MACE) which included all-cause death, non-fatal MI, target lesion revascularization (TLR), and target vessel revascularization (TVR). RESULTS: The average number of stents used per vessel was 1.4 ± 0.7. A total of 433 patients received ZES and 421 patients received EES. There was no significant difference in the incidence of 12-month MI, TLR, or TVR. All-cause death was found to be borderline significant between two groups (2.8% in ZES vs 0.9% in EES, p=0.05). The incidence of 12-month MACE in ZES and EES was 5.7% and 2.6% respectively, p=0.022. Stent thrombosis did not differ between groups (p=0.677). Kaplan-Meier analysis did not show significant difference for 12-month MACE-free survival between groups (log-rank p=0.158). It remained the same even after propensity adjustment for multiple confounders in Cox model (p=0.326). CONCLUSIONS: Implantation of ZES or EES provided comparable clinical outcomes with similar risk of 12-month MACE and death in STEMI patients with CKD undergoing primary PCI.

Comparison of peri-procedural platelet inhibition with prasugrel versus adjunctive cilostazol to dual anti-platelet therapy in patients with ST segment elevation myocardial infarction.

BACKGROUND: It has been well known that the inhibition of platelet aggregation (IPA) by anti-platelet agents was important to reduce the thrombo-embolic events in patients with ST segment elevation myocardial infarction (STEMI). However, the peri-procedural IPA by anti-platelet agents was not well known. METHODS: We compared the peri-procedural IPA between prasugrel and adjunctive cilostazol to dual anti-platelet therapy (triple anti-platelet therapy; TAP) in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). We prospectively randomized 70 consecutive clopidogrel-naive patients with STEMI planned PCI to either prasugrel [loading dose (LD) 60 mg; 37 patients] or TAP (LD aspirin 300 mg, clopidogrel 600 mg, and cilostazol 200mg; 33 patients). Primary end points of the study were the platelet reactivity unit (PRU) or % inhibition by the VerifyNow P2Y12 assay at pre-PCI and pre-discharge. RESULTS: The drug loading to pre-PCI time was similar between prasugrel and TAP groups (25.4 ± 10.42 min vs. 25.5 ± 10.56 min, p=0.957). PRU at pre-PCI was significantly lower in prasugrel than in TAP (269.1 ± 71.69 vs. 306.5 ± 48.67, p=0.012). The lower PRU and greater % inhibition also observed in prasugrel than in TAP at pre-discharge (108.2 ± 60.51 vs. 238.1 ± 73.40; 63.6 ± 18.51% vs. 16.8 ± 17.91%, p<0.001 respectively). No differences in in-hospital bleeding complications between the two groups were observed. CONCLUSION: Our study demonstrates that prasugrel could produce a significantly greater peri-procedural as well as in-hospital IPA compared with TAP in patients with STEMI undergoing primary PCI.

Progressive dilation of the left atrium and ventricle after acute myocardial infarction is associated with high mortality.

BACKGROUND AND OBJECTIVES: The purpose of this study is to identify the prevalence of progressive dilation in patients with acute myocardial infarction (AMI) combined with heart failure (HF) and determine the prognostic significance and associated factors with a geometric change of an infarcted heart. SUBJECTS AND METHODS: A total of 1310 AMI patients with HF (63.9±12.5 years, 70% male) between November 2005 and April 2011 underwent echocardiography at admission and one year later. Left ventricular (LV) remodeling is defined as 20% progression, and left atria (LA) remodeling is 10% compared with the initial volume index. RESULTS: The prevalence of both LA and LV remodeling was 13.9%; LV only was 9.3%, LA only 22.8% and non-remodeling was 55.1%, respectively. In the non-remodeling group, Killip class II was more frequent (83.9%, p<0.001) whereas in other remodeling groups, Killip class III was more frequent. Initial wall motion score index, ejection fraction, maximal cardiac enzyme, high sensitive C-reactive protein, B type natriuretic peptide, and triglyceride serum levels were significantly associated with heart remodeling. All causes of death occurred in 168 cases (12.8%) during the follow-up period. Mortality was the highest in the LV and LA remodeling group (20.9%) and the lowest in the non-remodeling group (11.4%). During the period of follow-up, the cumulative survival rate was significantly lower in the groups of LA and LV remodeling than in others (log rank p=0.006). CONCLUSION: Total mortality was significantly increased in patients AMI with geometrically progressive LA and LV dilatation.

Comparison of Coronary Plaque Components between Non-Culprit Lesions in Patients with Acute Coronary Syndrome and Target Lesions in Patients with Stable Angina: Virtual Histology-Intravascular Ultrasound Analysis.

BACKGROUND AND OBJECTIVES: The differences in plaque characteristics between non-culprit lesions (NCL) in acute coronary syndrome (ACS) patients (ACS-NCL) and target lesions (TL) in stable angina (SA) patients (SA-TL) are not well understood. We used a virtual histology-intravascular ultrasound (VH-IVUS) to compare the plaque components between ACS-NCL and SA-TL. SUBJECTS AND METHODS: We compared VH-IVUS findings between 290 ACS-NCL and 276 SA-TL. VH-IVUS classified the color-coded tissue into four major components: green (fibrotic); yellow-green (fibro-fatty); white {dense calcium (DC)}; and red {necrotic core (NC)}. Thin-cap fibroatheroma (TCFA) was defined as a NC ≥10% of the plaque area in at least 3 consecutive frames without overlying fibrous tissue in the presence of ≥40% plaque burden. RESULTS: Although the plaque burden was significantly smaller (52±13% vs. 54±14%, p=0.044), ACS-NCL had a greater %NC area (17.9±11.6% vs. 14.3±8.7%, p<0.001) and %DC area (9.7±9.8% vs. 8.1±8.0%, p=0.032) compared with SA-TL at the minimum lumen site. By volumetric analysis, ACS-NCL had a greater %NC volume (15.8±9.2% vs. 13.9±7.4%, p=0.006) compared with SA-TL. TCFA was observed more frequently in ACS-NCL compared with SA-TL (27.6% vs. 18.1%, p=0.032). Independent predictors of TCFA by multivariate analysis were ACS {odds ratio (OR): 2.204, 95% CI: 1.321-3.434, p=0.021} and high-sensitivity C-reactive protein (OR: 1.101; 95% CI 1.058-1.204, p=0.035). CONCLUSION: Although the plaque burden was significantly smaller, ACL-NCL had more vulnerable plaque components compared with SA-TL, and ACS and high-sensitivity C-reactive protein were the independent predictors of TCFA.

The impact of triple anti-platelet therapy for endothelialization and inflammatory response at overlapping bioabsorbable polymer coated drug-eluting stents in a porcine coronary model.

BACKGROUND: This study was conducted to evaluate the endothelialization and the inflammatory responses depending on the administration duration of triple anti-platelet therapy at overlapping bioabsorbable polymer coated biolimus-eluting stents (BESs) in a porcine coronary model. METHODS: We successfully deployed 36 overlapping BESs for the left anterior descending coronary and left circumflex artery or right coronary artery in 18 non-injured pigs. Total pigs were divided into 3 groups (12 overlapping stents of 6 pigs in each group) as follows: group I received aspirin 100mg and clopidogrel 75 mg daily for 8 weeks, group II received aspirin 100mg and clopidogrel 75 mg daily for 8 weeks and cilostazol 200mg daily for initial 4 weeks, and group III received aspirin 100mg, clopidogrel 75 mg, and cilostazol 200mg daily for 8 weeks. Follow-up coronary angiograms and histomorphometric and histopahtologic analyses at overlapping and non-overlapping segments were performed respectively. RESULTS: Inflammation score was similar between overlapping and non-overlapping segments in all pigs (1.2 ± 0.33 vs. 1.1 ± 0.17, p=0.117). The neointima area (NA) and percent area stenosis (%AS) at overlapping segments were not significantly different among the 3 groups. However, at non-overlapping segments, NA and %AS in group III were significantly smaller than those in group I (2.3 ± 0.50mm(2) vs. 1.8 ± 0.43 mm(2), p=0.037; 48.9 ± 12.85% vs. 37.7 ± 9.08%, p=0.031). CONCLUSIONS: Our study shows that BES appears to be reliable on the inflammatory response at overlapping segments as well as non-overlapping segments. Long-term administration of cilostazol is more effective in reducing neointimal formation at non-overlapping segments of BESs in a porcine coronary model.

Relation between poststenting peristent plaque components and late stent malapposition after drug-eluting stent implantation: virtual histology-intravascular ultrasound analysis.

BACKGROUND: Impact of plaque composition on late stent malapposition (LSM) after drug-eluting stent (DES) implantation has not been evaluated. METHODS: We evaluated the relation between plaque components at poststenting peristent area (between external elastic membrane and stent areas) and LSM after DES implantation in 266 patients (314 native lesions; paclitaxel-eluting stent in 205 lesions, sirolimus-eluting stent in 66 lesions, zotarolimus-eluting stent in 32 lesions and everolimus-eluting stent in 11 lesions) in whom virtual-histology intravascular ultrasound was performed at index (poststenting) and follow-up (mean: 11.7 ± 4.8 months). RESULTS: LSM occurred in 24 patients with 30 lesions (9.6%) and there were no significant differences in the incidences of LSM among 4 DES groups [21/205 (10.2%) in paclitaxel-eluting stent, 6/66 (9.1%) in sirolimus-eluting stent, 2/32 (6.3%) in zotarolimus-eluting stent and 1/11 (9.1%) in everolimus-eluting stent, p=0.5)]. Patients with LSM were presented with more acute myocardial infarction (50% vs. 28%, p=0.026) and were more diabetics (50% vs. 30%, p=0.030) compared with those without LSM. Lesions with LSM had more poststenting peristent %necrotic core (NC) volume compared with those without LSM (25.8 ± 11.1% vs. 21.0 ± 5.7%, p<0.001). Independent predictors of LSM were poststenting peristent %NC volume [odds ratio (OR); 1.216, 95% CI; 1.053-1.405, p=0.008], acute myocardial infarction (OR; 2.897, 95% CI; 1.675-4.118, p=0.029), and diabetes mellitus (OR; 2.413, 95% CI; 1.543-3.996, p=0.038). CONCLUSIONS: Poststenting peristent NC component especially in patients with acute myocardial infarction and in those with diabetes mellitus is associated with the development of LSM after DES implantation.