Benefit of complete revascularization in patients with multivessel coronary disease in the drug-eluting stent era.

BACKGROUND: The benefit of complete (CR) vs. incomplete revascularization (IR) with drug-eluting stent (DES), unlike with bypass grafting, is not well established in patients with multivessel coronary artery disease (MVD). METHODS AND RESULTS: Consecutive patients from a single center DES registry who were newly diagnosed as having MVD and who underwent successful percutaneous coronary intervention between March 2003 and December 2009 were traced for the occurrence of death, myocardial infarction (MI), and repeat revascularization. Among 845 patients (337 with CR and 508 with IR), propensity score-matched 275 pairs were followed for a median of 3.9 years. The adjusted hazard ratio (HR) of CR [95% confidence interval] was 0.66 [0.34-1.28] for death; 0.51 [0.28-0.95] for death and MI; 0.84 [0.60-1.19] for death, MI, and repeat revascularization. The observed benefit of CR was also cardiac-specific. The adjusted HR of CR for cardiac death and MI was 0.39 [0.16-0.96]. In 3 subgroups of patients with diabetes (n=191), ejection fraction <55% (n=153) and estimated glomerular filtration rate (eGFR) <60 ml/min (n=170), the benefit of CR was pronounced with the adjusted HR for cardiac death and MI of 0.27 [0.08-0.93], 0.18 [0.05-0.68] and 0.27 [0.07-0.99], respectively. CONCLUSIONS: In MVD patients treated with DES, CR was associated with the long-term benefit in reducing any or cardiac death and MI. The main beneficiaries of CR were those with diabetes, low ejection fraction and low eGFR.

Effects of deferred versus immediate stenting on left ventricular function in patients with ST elevation myocardial infarction.

BACKGROUND: Previous studies have shown conflicting results on the benefits of deferred stenting (DS) in infarct size and the incidence of microvascular obstruction in patients with ST elevation myocardial infarction (STEMI). However, effect of DS on left ventricular (LV) function was not known. We aimed to evaluate whether DS improve LV function and relevant clinical outcomes after STEMI, using follow-up data from the INNOVATION study (NCT02324348). METHODS: In total, 114 patients were randomly assigned to DS group or immediate stenting (IS) group at a 1:1 ratio. LV functional remodeling indices and MACE (major adverse cardiac events: a composite of death, non-fatal MI, unplanned target vessel revascularization, or hospitalization due to heart failure) were compared between DS and IS groups. RESULTS: Serial echocardiographic analyses were completed in 89 subjects (78%). There were no significant changes in LV volume in either group. While LV ejection fraction and wall motion score index (WMSI) improved in both groups during follow-up, the increments were not statistically different between the 2 groups (4.3 ±â€Š8.2 vs 3.2 ±â€Š7.1, P = .504 for ΔLV ejection fraction; -0.16 ±â€Š0.25 vs -0.16 ±â€Š0.25, P = .99 for ΔWMSI). However, E/e'' was decreased and e' was increased only in the DS group (-3.31 ±â€Š5.60 vs -0.46 ±â€Š3.10, P = .005 for ΔE/e'; 0.77 ±â€Š1.71 vs -0.22 ±â€Š1.64, P = .009 for Δe'). The incidence of major adverse cardiac events was numerically lower in the DS group than in the IS group without a statistical significance at 1-year follow-up. CONCLUSIONS: Routine DS improved LV diastolic function but not systolic function compared with IS in patients with STEMI.

Determinants of surgical outcome in patients with isolated tricuspid regurgitation.

BACKGROUND: We sought to identify preoperative predictors of clinical outcomes after surgery in patients with severe tricuspid regurgitation. METHODS AND RESULTS: We prospectively enrolled 61 consecutive patients (54 women, aged 57+/-9 years) with isolated severe tricuspid regurgitation undergoing corrective surgery. Twenty-one patients (34%) were in New York Heart Association functional class II, 35 (57%) in class III, and 5 (9%) in class IV. Fifty-seven patients (93%) had previous history of left-sided valve surgery. Preoperative echocardiography revealed pulmonary artery systolic pressure of 41.5+/-8.7 mm Hg, right ventricular (RV) end-diastolic area of 35.1+/-9.0 cm(2), and RV fractional area change of 41.3+/-8.4%. The median follow-up duration after surgery was 32 months (range, 12 to 70). Six of the 61 patients died before discharge; thus, operative mortality was 10%. Three of the 55 patients who survived surgery died during follow-up, and 6 patients required readmission because of cardiovascular problems. Thus, 46 patients (75%) remained event free at the end of follow-up. In the 54 patients who underwent 6-month clinical and echocardiographic follow-up, RV end-diastolic area decreased by 29%, with a corresponding 26% reduction in RV fractional area change. Thirty-three patients (61%) showed improved functional capacity after surgery. On multivariable Cox regression analysis, preoperative hemoglobin level (P<0.001) and RV end-systolic area (P<0.001) emerged as independent determinants of clinical outcomes. On receiver operating characteristic curve analysis, we found that RV end-systolic area <20 cm(2) predicted event-free survival with a sensitivity of 73% and a specificity of 67%, and a hemoglobin level >11.3 g/dL predicted event-free survival with a sensitivity of 73% and a specificity of 83%. CONCLUSIONS: Timely correction of severe tricuspid regurgitation carries an acceptable risk and improves functional capacity. Surgery should be considered before the development of advanced RV systolic dysfunction and before the development of anemia.

'Real world' comparison of drug-eluting stents vs bare metal stents in the treatment of unselected patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: Concerns exist regarding the long-term efficacy and safety of drug-eluting stents (DES) in patients with ST-segment elevation myocardial infarction (STEMI). The study aimed to compare the mid- to long-term outcomes of DES vs bare metal stents (BMS) in patients with STEMI in a real-world setting. METHODS AND RESULTS: Six hundred and eighty four consecutive patients with STEMI who underwent percutaneous coronary intervention from January 2003 to December 2006 were analyzed; 539 patients (78.8%) with DES and 145 (21.2%) with BMS. Patients were followed for the occurrence of target vessel failure (TVF); a composite of cardiac death, non-fatal myocardial infarction, or target vessel revascularization (TVR). After a follow-up duration of 36 months, the TVF rate was significant lower in the DES group compared with the BMS group (17.8% vs 34.5%, P<0.01), which was mainly driven by a decrease in TVR (9.1% vs 22.8%, P<0.01). Diabetic patients, those with multivessel disease and those treated with smaller or longer stents benefited more from DES implantation. Propensity score matching concordantly indicated a benefit of DES with regard to TVF (13.5% vs 34.2%; P<0.01). The overall incidence of stent thrombosis (ST) in each group was comparable (3.9% vs 4.1%, P=0.47). CONCLUSIONS: Compared to BMS, the mid- to long-term outcome was better in patients receiving DES for acute STEMI. This was driven mainly by a reduction in repeat revascularization.

Vitamin K epoxide reductase complex subunit 1 gene polymorphism is associated with atherothrombotic complication after drug-eluting stent implantation: 2-Center prospective cohort study.

BACKGROUND: Single nucleotide polymorphisms of vitamin K epoxide reductase complex subunit 1 (VKORC1) was reported to have association with arterial vascular disease. We investigated whether single nucleotide polymorphism of VKORC1 +2255 is associated with clinical outcomes among patients who underwent drug-eluting stent (DES) implantation. METHODS: We prospectively collected genomic DNA in patients who underwent DES deployment from September 2003 to December 2006 and compared clinical outcomes according to their VKORC1 genotype at the locus + 2255 (rs 2359612). The primary end point was composite of atherothrombotic events (cardiac death, myocardial infarction, and nonhemorrhagic stroke). RESULTS: Mean follow-up duration was 631 +/- 251 days. Genotyping was completed in 764 cases (TT genotype [n = 640, 83.8%] vs non-TT [CC or CT] genotype [n = 124, 16.2%]). Non-TT group showed more composite events than TT group (7.3% vs 3.0%, P = .032). In the Cox regression analysis, non-TT genotype of VKORC gene was a significant predictor of atherothrombotic events (hazard ratio 2.56, 95% confidence interval 1.14-5.78). In the event-free survival analysis, non-TT group also showed significantly poorer cardiovascular events-free survival rate than TT group (P = .02). CONCLUSIONS: VKORC1 genotype is associated with cardiovascular events in patients with DES implantation, suggesting the role of coagulation system.

N-acetylcysteine versus AScorbic acid for preventing contrast-Induced nephropathy in patients with renal insufficiency undergoing coronary angiography NASPI study-a prospective randomized controlled trial.

BACKGROUND: Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired renal failure and affects mortality and morbidity. There has been no study comparing the efficacy of N-acetylcysteine (NAC) and ascorbic acid that have potential for CIN prevention in patients with renal insufficiency. METHODS: We conducted a prospective randomized controlled trial. A total of 212 patients who had pre-existing renal impairment with basal creatinine clearance < or =60 mL/min and/or serum creatinine (SCr) level of > or =1.1 mg/dL, were randomized to have either high-dose NAC (1,200 mg orally twice a day before and on the day of coronary catheterization, n = 106) or ascorbic acid (3 g and 2 g orally before, and 2 g twice after coronary catheterization with a 12-hour interval, n = 106). The primary end point was the maximum increase of SCr level, and the secondary end point was the incidence of CIN. RESULTS: The maximum increase of SCr level was significantly lower in NAC group than in ascorbic acid group as follows: -0.03 +/- 0.18 mg/dL versus 0.04 +/- 0.20 mg/mL, respectively (P = .026). Patients with diabetes or who had received a high dose of contrast media experienced significantly less rise of SCr level with NAC than ascorbic acid; in diabetic subgroup, -0.05 +/- 0.22 mg/dL versus 0.09 +/- 0.29 mg/mL, respectively (P = .020); in patients with high dose of dye, -0.03 +/- 0.17 mg/dL versus 0.04 +/- 0.21 mg/mL, respectively (P = .032). The incidence of CIN, the secondary end point, tended to be in favor of NAC rather than ascorbic acid, 1.2% versus 4.4%, respectively (P = .370). Notably, among the diabetes patients, the NAC significantly lowered CIN rate than ascorbic acid, 0% (0/38) versus 12.5% (4/32), respectively (P = .039). CONCLUSION: High-dose NAC seems more beneficial than ascorbic acid in preventing contrast-induced renal function deterioration in patients, especially diabetic patients, with renal insufficiency undergoing coronary angiography.

The incidence and predictors of postprocedural incomplete stent apposition after angiographically successful drug-eluting stent implantation.

OBJECTIVES: The aim of this study was to evaluate the incidence and predictors of postprocedural incomplete stent apposition (ISA) after angiographically successful drug-eluting stent (DES) implantation. BACKGROUND: The deployed stents are usually evaluated by angiography alone; however, there are possibilities of postprocedural ISA despite the angiographically successful implantation. METHODS: A total of 339 lesions in which poststent intravascular ultrasound (IVUS) was performed after successful DES implantation was included. Paclitaxel-eluting stents were implanted in 237 lesions and sirolimus-eluting stents (SES) in 102 lesions. Clinical, angiographic and procedural characteristics and IVUS findings for all cases were analyzed. RESULTS: The overall incidence of ISA was 13.9% (47/339). By multivariate analysis, male gender (OR: 2.36, 95% CI: 1.09-5.11), deployment of SES (OR: 2.90, 95% CI: 1.49-5.67), the presence of intracoronary thrombus (OR: 7.47, 95% CI: 1.67-33.47), and non-ST elevation myocardial infarction (OR: 2.73, 95% CI: 1.09-6.83) were independent predictors for postprocedural ISA after angiographically successful DES implantation. CONCLUSIONS: The incidence of postprocedural ISA after angiographically successful implantation of DES was not infrequent. A DES deployment strategy incorporating IVUS guidance might be helpful to reduce the incidence of postprocedural ISA.

Effect of celecoxib on restenosis after coronary angioplasty with a Taxus stent (COREA-TAXUS trial): an open-label randomised controlled study.

BACKGROUND: In-vitro and animal experiments have shown that the cyclo-oxygenase 2 inhibitor celecoxib can reduce formation of neointima within stents. We aimed to test whether celecoxib has similar effects in a clinical setting. METHODS: In a randomised two-centre trial, we enrolled 274 patients who had angina pectoris or a positive stress test and who had native coronary artery lesions for which implantation of paclitaxel-eluting stents was feasible. All patients were given aspirin (100 mg daily) and clopidogrel (75 mg daily). 136 patients were randomly assigned to receive celecoxib (400 mg before the intervention, and 200 mg twice daily for 6 months after the procedure). The primary endpoint was late luminal loss on quantitative coronary angiography at 6 months after the intervention. Secondary endpoints were cardiac death, non-fatal myocardial infarction, and revascularisation of the target lesion. Analysis was done on a modified intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00292721. FINDINGS: At 6 months, mean in-stent late luminal loss was lower in the celecoxib group (0.49 mm, SD 0.47) than in the control group (0.75 mm, 0.60) (absolute difference 0.26 mm; 95% CI 0.12-0.40). Frequency of secondary outcomes at 6 months was also lower in the celecoxib group, mainly because of a reduced need for revascularisation of the target lesion. INTERPRETATION: These data suggest that the adjunctive use of celecoxib for 6 months after stent implantation in patients with coronary artery disease is safe and can reduce the need for revascularisation of the target lesion.

Development of tricuspid regurgitation late after left-sided valve surgery: a single-center experience with long-term echocardiographic examinations.

OBJECTIVES: This study sought to investigate the incidence and identify the predictors of significant tricuspid regurgitation (TR) development long after left-sided valve surgery. METHODS: Of 615 patients who underwent surgery for left-sided valve disease between 1992 and 1995, 335 patients without significant TR who completed at least 5 years of clinical and echocardiographic follow-up were enrolled. Late significant TR development was assessed by echocardiography with a mean follow-up duration of 11.6 +/- 2.1 years. RESULTS: Significant late TR was found in 90 patients (26.9%). Patients with late TR showed an advanced age (47.6 +/- 13.4 vs 44.3 +/- 13.2 years, P = .04), a higher prevalence of preoperative atrial fibrillation (83.3 vs 46.5%, P < .001), a greater left atrial dimension (56.9 +/- 13.2 vs 52.4 +/- 11.5 mm, P = .006), and a higher prevalence of prior valve surgery (40.0 vs 25.3%, P = .01). In addition, late TR occurred more frequently in patients who had undergone mitral valve surgery than in those who did not (93.3 vs 72.2%, P < .001). However, multivariate analysis showed that the presence of preoperative atrial fibrillation (odds ratio 5.37; 95% CI 2.71-10.65; P < .001) was the only independent factor of late TR development. Patients who developed late TR had a lower event-free survival rate than those who did not (P = .03). CONCLUSIONS: The development of significant TR long after left-sided valve surgery is not uncommon with an estimated incidence of 27% and is closely associated with a poor prognosis. The presence of preoperative atrial fibrillation was identified as the only independent predictor of the development of late TR.

Prevention of radiocontrast medium-induced nephropathy using short-term high-dose simvastatin in patients with renal insufficiency undergoing coronary angiography (PROMISS) trial--a randomized controlled study.

BACKGROUND: Contrast media cause oxidative stress, which has been suggested as one possible mechanism responsible for contrast-induced nephropathy. Statins appear to have pleiotropic effects, including antioxidant properties. We investigated to determine whether simvastatin pretreatment reduces the risk of contrast-induced nephropathy in a high-risk population of patients with renal insufficiency undergoing coronary angiography. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled, 2-center trial, involving 247 consecutive patients with chronic renal insufficiency (calculated creatinine clearance < or = 60 mL/min and/or serum creatinine > or = 1.1 mg/dL) undergoing coronary angiography. Patients were randomized to simvastatin (n = 124; 160 mg total, 40 mg orally every 12 hours starting the evening before and ending the morning after the procedure) or placebo (n = 123). All patients received pre - and postprocedure hydration. The iso-osmolar contrast agent iodixanol was used for coronary angiography in all patients. RESULTS: There was no difference between simvastatin and placebo in mean peak increase in serum creatinine measured within 48 hours after coronary angiography, the primary study end point (0.002 +/- 0.164 vs 0.017 +/- 0.230 mg/mL respectively, P = .559). The incidence of contrast-induced nephropathy, a secondary end point defined as increase of either > or = 25% or > or = 0.5 mg/dL in serum creatinine, was 2.5% in simvastatin-treated patients (3/118) and 3.4% in placebo-treated patients (4/118), a nonsignificant difference (P = 1.00). There were also no differences between the 2 groups in length of hospital stay or 1- and 6-month clinical outcomes. CONCLUSIONS: Simvastatin pretreatment for short-term at high dose do not prevent renal function deterioration after administration of contrast medium in patients with baseline renal insufficiency undergoing coronary angiography.

Echocardiographic and hemodynamic findings in patients with mitral stenosis undergoing percutaneous mitral commissurotomy comparing those with chronic atrial fibrillation versus those with normal sinus rhythm.

Chronic atrial fibrillation (AF) is common in patients with mitral stenosis (MS). Because AF induces electrical and mechanical remodeling of the left atrium, left atrial (LA) compliance is likely to be changed in its presence. This study was performed to investigate the influence of AF on LA compliance in patients with moderate to severe MS. Data were analyzed for 356 patients (282 women; mean age 40 +/- 11 years; range 17 to approximately 71) who were registered in the percutaneous mitral commissurotomy database. Mean LA pressure was lower (21 +/- 7 vs 26 +/- 8 mm Hg; p <0.001), but LA volume was higher in the AF than sinus-rhythm group (126 +/- 62 vs 74 +/- 27 ml; p <0.001), indicating higher LA compliance, which was further confirmed by lower LA v wave at catheterization in the AF group (27 +/- 9 for AF vs 32 +/- 10 mm Hg for sinus rhythm; p <0.001). In conclusion, the presence of AF has a significant influence on LA compliance in patients with moderate to severe MS.

Common adrenergic receptor polymorphisms as novel risk factors for vasospastic angina.

BACKGROUND: Sympathetic activity mediated by adrenergic receptors (ARs) appears to play an important role in controlling the vasomotor tone and, thus, may be associated with vasospastic angina (VA). We investigated the association of the common functional polymorphisms of the AR gene and VA. The candidates were alpha2CDel322-325, beta1Gly389Arg, beta2Arg16Gly, and beta2Gln27Glu polymorphisms. METHODS: Eighty-two patients with VA, confirmed by coronary angiography with or without ergonovine provocation test, and 114 apparently healthy control subjects were investigated for genotype of 4 AR polymorphisms and established risk factors of ischemic heart disease. RESULTS: The minor alleles were alpha2CDel322-325, beta1Gly389, beta2Gly16, and beta2Glu27 and their frequencies were 7%, 18%, 42%, and 29%, respectively, in the control subjects of this Korean population, which were different from those of other ethnic groups. On univariate analysis, age, smoking, male sex, alpha2CDel322-325 allele carrier state, and beta2Gln27 homozygote state were significant risk factors for VA. After multivariate analysis using multiple logistic regression model, age (odds ratio [OR] 1.809, CI 1.046-1.135, P < .0001), smoking (OR 4.902, CI 2.105-11.416, P = .0002), alpha2CDel322-325 allele carrier state (OR 5.132, CI 2.094-12.578, P = .0003), and beta2Gln27 allele homozygosity (OR 3.152, CI 1.364-7.285, P = .0072) remained as independent risk factors. In the combined genotype analysis, the effect of beta2Gln27 allele was evident only when the alpha2CDel322-325 allele was absent. CONCLUSIONS: The alpha2CDel322-325 allele carrier state and beta2Gln27 allele homozygote state were identified as novel risk factors of VA in this Korean population. This result suggests the importance of the adrenergic stimuli and the genetic background in the pathogenesis of the VA.

Prediction of outcome in patients undergoing surgery for severe tricuspid regurgitation following mitral valve surgery and role of tricuspid annular systolic velocity.

This study was performed to identify echocardiographic parameters related to postoperative clinical outcome in patients who undergo surgery for severe tricuspid regurgitation after mitral valve surgery. Eighteen patients (2 men, 16 women; mean age 58 years) were prospectively enrolled. Echocardiographic examinations were performed before and 15 +/- 7 months after surgery. Favorable postoperative clinical outcome was defined as an improvement of > or = 1 in New York Heart Association functional class or a > 25% increase in respiratory variation of inferior vena cava diameter. Operative mortality was 11% (2 of 18). Of the 16 survivors, 9 (56%) achieved favorable postoperative clinical outcomes. Only systolic tricuspid annulus velocity (S'T) was found to be associated with postoperative clinical outcome (favorable vs unfavorable postoperative clinical outcome 12.9 +/- 2.1 vs 9.7+/- 1.7 cm/s, p < 0.05). For S'T < 9.5 cm/s, the sensitivity, specificity, and positive and negative predictive values for predicting an unfavorable postoperative clinical outcome were 67%, 100%, 100%, and 75%, respectively. In conclusion, S(T') can predict postoperative clinical outcomes in these patients.

Determinants of the severity of functional tricuspid regurgitation.

We performed a prospective study of patients with chronic right ventricular (RV) dilation to determine the factors associated with the degree of functional tricuspid regurgitation (FTR). We prospectively enrolled 64 patients with chronic RV dilation and measured right atrial (RA) area, RV area and its fractional area change (RVFAC), tricuspid annular diameter and contraction, tricuspid valve (TV) tethering area, and systolic pulmonary artery pressure. We also measured the RV eccentricity index and the RV sphericity index for simple presentation of RV geometry. Regurgitant orifice area of FTR was obtained for the quantification of FTR. End-systolic RV eccentricity index (r=0.73), end-diastolic RV eccentricity index (r=0.56), RA area (r=0.49), TV tethering area (r=0.37), age (r=0.31), end-systolic (r=0.42) and end-diastolic (r=0.30) tricuspid annular diameters, and left ventricular ejection fraction (r=-0.37) were significantly related to the regurgitant orifice area of FTR in univariate analysis. However, RV area, RVFAC, and systolic pulmonary artery pressure were not. In multivariate analysis, the end-systolic RV eccentricity index (p<0.001), TV tethering area (p=0.003), and end-diastolic tricuspid annulus diameter (p=0.007) showed the independent associations with regurgitant orifice area of FTR. The sensitivities and specificities for predicting more than mild FTR were found to be 79% and 82% with an end-systolic RV eccentricity index>2.0, 69% and 73% with an end-systolic tethering area>1.0 cm2, and 64% and 59% for an end-systolic tricuspid annulus diameter>3.9 cm, respectively. FTR severity was found to show the best correlation with the end-systolic RV eccentricity index. In conclusion, these findings underscore the importance of eccentric RV dilation for determining FTR severity and should lead to the development of more rational surgical approaches to FTR beyond TV annuloplasty.

Physiological and clinical relevance of anomalous right coronary artery originating from left sinus of Valsalva in adults.

OBJECTIVE: To examine physiological and clinical relevance of an anomalous right coronary artery originating from left sinus of Valsalva (right ACAOS) with interarterial course in adults. METHODS AND RESULTS: For physiological assessment, fractional flow reserve (FFR) during dobutamine challenge was measured in 37 consecutive adult patients with lone right ACAOS with interarterial course. At baseline, mean FFR was 0.91±0.06, declining to 0.89±0.06 upon dobutamine infusion (p<0.001). Dobutamine stress FFR was significant (≤0.8) in three patients (8.1%), two of whom were surgically treated. Following surgery, dobutamine stress FFR rose from 0.76 to 0.94 and 0.76 to 0.98. Remodelling index (r=0.583, p=0.002), minimal lumen area (diastole: r=0.580, p=0.002; systole: r=0.0618, p<0.001) and per cent area stenosis (r=-0.550, p=0.004), measured by intravascular ultrasound, correlated with dobutamine stress FFR. To assess the clinical relevance, follow-up data of 119 patients with lone right ACAOS with interarterial course were analysed retrospectively. Two deaths occurred during a median follow-up period of 4 years, for a mortality rate of 0.34 per 100 person-year. No instances of myocardial infarction were recorded and one patient did undergo surgical revascularisation in the course follow-up. CONCLUSIONS: Most instances of lone right ACAOS with interarterial course discovered in adults were physiologically insignificant and ran benign clinical courses. Conservative management may thus suffice in this setting if no definitive signs of myocardial ischaemia are evident.

NF-kappaB decoy potentiates the effects of radiation on vascular smooth muscle cells by enhancing apoptosis.

NF-kappaB promotes cell survival against external stress such as radiation. We examined whether NF-kappaB decoy transfection enhances the antiproliferative effects of radiation on vascular smooth muscle cells (VSMCs) in vitro. The irradiation induced activation or nuclear translocation of NF-kappaB p65 in VSMCs was confirmed by immunofluorescence. NF-kappaB decoy transfection resulted in inhibition of the radiation-induced NF-kappaB activation in VSMCs and the subsequent reduction of transcription and translocation of ICAM, iNOS, and TNF-alpha, downstream molecules under the control of NF-kappaB. By using MTT assay, NF-kappaB decoy augmented the antiproliferative effects of radiation, where the effect of low dose radiation (2 and 8-Gy) of the cells transfected with NF-kappaB decoy was equivalent to the high dose (16-Gy) irradiated non-transfected cells at 48 h after irradiation: 1.06+/-0.16, 1.11+/-0.22, 1.20+/-0.25, respectively. The decrease in proliferation and survival of the radiation treated cells by flow cytometry analysis showed that NF-kappaB inhibition did not show any additive effects on the cell cycle of the irradiated VSMCs, while apoptosis was significantly increased after NF-kappaB decoy transfection in the irradiated VSMCs (apoptosis fraction: 13.33+/-2.08% vs. 26.29+/-7.43%, for radiation only vs. radiation+NF-kappaB decoy transfection, P < 0.05). In addition, at 48 h, NF-kappaB decoy transfection dose dependently (10 microM vs. 20 microM) inhibited proliferation of 16Gy-irradiated VSMCs, and showed greater antiproliferative efficacy than 100 microM sulfasalazine, a specific NF-kappaB inhibitor. These results indicate that NF-kappaB inhibition reduces proliferation and survival of irradiated VSMCs, likely by increased apoptosis rather than additive cell cycle arrest and suggest the possibility of adjunctive gene therapy using NF-kappaB decoy to improve efficacy and to decrease the adverse effects of intracoronary radiation therapy.

Renal dysfunction and high levels of hsCRP are additively associated with hard endpoints after percutaneous coronary intervention with drug eluting stents.

BACKGROUND: Chronic kidney disease (CKD) and high C-reactive protein (CRP) are known risk factors of cardiovascular disease. In the drug eluting stent (DES) era, the relationship among CKD, CRP, and long-term outcomes after percutaneous coronary intervention (PCI) has not yet been demonstrated. We investigated the combined effects of renal dysfunction and CRP on outcomes in patients who underwent PCI using DES. METHODS: A total of 1859 patients (mean age 64 ± 10 years) who underwent PCI with DES between February 2003 and June 2006, were divided into 4 groups (quartile) according to estimated glomerular filtration rate (eGFR) and hsCRP at admission. RESULTS: The composite of cumulative death and non-fatal myocardial infarction (mortality+MI) during median follow-up of 27 months, was significantly higher in the lowest eGFR quartile than in the other three groups (hazard ratio (HR) for mortality+MI: 3.32, 95% CI: 2.21-5.00, P<0.001). Mortality+MI was also significantly higher in the highest hsCRP quartile (HR: 3.29, 95% CI: 2.02-5.37, P<0.001). A combined analysis of mortality+MI on the basis of hsCRP and renal function showed the exaggerated hazard in the combined worst quartile of hsCRP and GFR (HR of the combined worst quartile, 10.876, 95% CI: 3.74-31.63, P<0.001). Furthermore, both the lowest eGFR quartile and the highest hsCRP quartile were significantly associated with increased risk of stent thrombosis. In a multivariate analysis, low GFR and high hsCRP were independent predictors of mortality+MI after PCI with DES along with left ventricular dysfunction, diabetes, and left main disease. CONCLUSIONS: In an unselected cohort of patients receiving PCI with DES, poor renal function and high hsCRP were additively associated with a higher risk of hard endpoints and were independent predictors of mortality+MI even after correction for other factors. Our data suggest the importance of systemic factors on mortality even in the DES era.

Effects of the aging process on left ventricular systolic and diastolic synchronicity indexes: insights from 160 "completely" healthy volunteers.

BACKGROUND: Growing attempt to use left ventricular (LV) systolic (LVSIsys) and diastolic (LVSIdia) synchronicity indexes in the process of selecting potential responders to cardiac resynchronization therapy has created a need for normative reference values. HYPOTHESIS: This study sought: (1) to determine normal reference ranges for LVSIsys and LVSIdia, and (2) to assess their relationships to age and conventional parameters reflecting LV systolic and diastolic functions. METHODS: We recruited 160 healthy volunteers (104 men) free of any systemic or cardiovascular disease. Maximal difference and standard deviation of time to peak systolic and peak early diastolic myocardial velocities for LVSIsys and LVSIdia were measured using 6 and 12 segment models. RESULTS: Normal ranges for LVSIsys and LVSIdia obtained in this study were slightly higher than previously reported. The normal aging process did not significantly change LVSIsys, whereas LVSIdia progressively and consistently increased with age. Significant correlations were observed between LVSIdia and parameters representing LV diastolic function, that is, early mitral inflow velocity and its deceleration time, and early mitral annulus velocity. A physiologic increase in LV mass/Ht²·7 showed a weak, but significant correlation with LVSIdia (r = 0.15-0.22), but not with LVSIsys. On multivariate analysis, an age-dependent increase in LVSIdia was confirmed. CONCLUSIONS: In this study, we propose age-specific reference ranges for LVSIsys and LVSIdia. LVSIsys remains stable throughout age groups, whereas LVSIdia progressively increases with age. We believe that the reference values provided here will be useful for defining abnormal LV synchronous contraction and relaxation.

Long-term outcome of adjunctive celecoxib treatment after paclitaxel-eluting stent implantation for the complex coronary lesions: two-year clinical follow-up of COREA-TAXUS trial.

BACKGROUND: In the COREA-TAXUS trial ("Effect of Celecoxib On REstenosis after coronary Angioplasty with a TAXUS stent"), celecoxib reduced late luminal loss and adverse cardiac events at follow-up around 6 months. The objective of this study was to assess the long-term outcome of short-term adjunctive celecoxib treatment after paclitaxel-eluting stent implantation. METHODS AND RESULTS: This is a 2-year clinical follow-up of the COREA-TAXUS trial, an open-label randomized controlled study. A total 274 patients were randomized to receive or not receive celecoxib (400 mg before the intervention and 200 mg twice daily for 6 months after the procedure), and 271 underwent successful paclitaxel-eluting stent implantation. All patients were given aspirin (100 mg daily indefinitely) and clopidogrel (75 mg daily for at least 6 months). Among the 271 patients, 267 (98.5%) completed the 2-year clinical follow-up. From the previous follow-up to 2 years, there was no difference in the rate of adverse cardiac events between the celecoxib and control groups (1.6% versus 4.3%, P=0.27). Thus, at 2 years, the rate of adverse cardiac events was consistently lower in the celecoxib group (6.9% versus 19.7%, P=0.002). A significant reduction in need for target lesion revascularization was observed (6.2% versus 18.2%, P=0.003). The efficacy benefit in the celecoxib group was not undermined by an increased risk for cardiac death or myocardial infarction at 2 years (1.5% versus 1.4%). CONCLUSIONS: Six-month adjunctive celecoxib treatment after paclitaxel-eluting stent implantation was associated with durable long-term efficacy up to 2 years. However, the inconclusive evidence for the long-term safety of this treatment warrants caution. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00292721.

Comparison of triple antiplatelet therapy including triflusal and conventional dual therapy in patients who underwent drug-eluting stent implantation.

Triflusal is a derivative of acetylsalicylic acid but it exhibits different pharmacological and pharmacokinetic properties. The object of this study was to evaluate the efficacy of additional use of triflusal in patients who underwent drug-eluting stent implantation. First, we prospectively tested platelet function with a rapid platelet function analyzer (VerifyNow-Aspirin) in patients with stable angina (male, age, 61.6 +/- 8.3, body weight, 69.3 +/- 11.2 kg) who maintained dual (aspirin 100 mg and clopidogrel 75 mg per day, n = 23) or triple (aspirin 100 mg, clopidogrel 75 mg, and triflusal 300 mg per day, n = 23) therapy for more than one month. They were randomly assigned to a group. The triple group showed superior inhibition of arachidonic acid induced platelet aggregation compared to the dual group (420.2 +/- 47.7 ARU versus 465.0 +/- 71.2 ARU, P = 0.016). Second, we compared composite outcomes (death, myocardial infarction, and nonhemorrhagic stroke) after drug-eluting stent (DES) implantation between the dual (n = 1474) and triple (n = 433) groups in the prospective Seoul National University Hospital drug-eluting stent (SNUH-DES) cohort. The triple group had more current smokers, male patients, and patients with a previous history of revascularization. Also, the triple group underwent more complex interventions such as left main, chronic total occlusion, long lesion, and restenotic lesion than the dual group. In spite of their higher risk profiles, the triple group patients showed comparable composite outcomes (19 cases, 4.4%) to those of the dual group ones (41 cases, 2.8%) (P = 0.12). The triflusal-based triple antiplatelet therapy achieved superior platelet inhibition compared to the dual therapy ex vivo and it could be applied after complex intervention with DES.