Sodium-Glucose Cotransporter-2 Inhibitors After Acute Myocardial Infarction in Patients With Type 2 Diabetes: A Population-Based Investigation.

Background Whether the early use of sodium-glucose cotransporter-2 (SGLT2) inhibitors have cardioprotective effects following acute myocardial infarction is unknown. Thus, we aimed to evaluate the association between the early initiation of SGLT2 inhibitors and cardiac event rates in patients with diabetes with acute myocardial infarction undergoing percutaneous coronary intervention. Methods and Results Based on the National Health Insurance claims data in South Korea, patients who received percutaneous coronary intervention for acute myocardial infarction between 2014 and 2018 were analyzed. Patients given SGLT2 inhibitors or other glucose-lowering drugs were matched based on a propensity score. The primary end point was a composite of all-cause mortality and hospitalizations for heart failure. Major adverse cardiac events (a composite of all-cause death, nonfatal myocardial infarction, and ischemic stroke) were compared as the secondary end point. After 1:2 propensity score matching, the SGLT2 inhibitors group (938 patients) and the no use of SGLT2 inhibitors group (1876 patients) were compared. During a median follow-up of 2.1 years, the early use of SGLT2 inhibitors was associated with lower risks of both the primary end point (9.8% versus 13.9%; adjusted hazard ratio [HR], 0.68 [95% CI, 0.54-0.87]; P=0.002) and secondary end point (9.1% versus 11.6%; adjusted HR, 0.77 [95% CI, 0.60-0.99]; P=0.04). All-cause mortality and hospitalizations for heart failure were also significantly lower in early users of SGLT2 inhibitors. Conclusions The early use of SGLT2 inhibitors in patients with diabetes treated with percutaneous coronary intervention for acute myocardial infarction was associated with a significantly lower risk of cardiovascular events, including all-cause mortality, hospitalizations for heart failure, and major adverse cardiac events.

Edoxaban-based long-term antithrombotic therapy in patients with atrial fibrillation and stable coronary disease: Rationale and design of the randomized EPIC-CAD trial.

BACKGROUND: Anticoagulants are the standard therapy for patients with atrial fibrillation (AF) and antiplatelet therapy for those with coronary artery disease (CAD). However, compelling clinical evidence is still lacking regarding the long-term maintenance strategy with the combination of anticoagulant and antiplatelet drugs in patients with AF and stable CAD. DESIGN: The EPIC-CAD trial is an investigator-initiated, multicenter, open-label randomized trial comparing the safety and efficacy of 2 antithrombotic strategies in patients with high-risk AF (CHA2DS2-VASc score ≥ 2 points) and stable CAD (≥6 months after revascularization for stable angina or ≥12 months for acute coronary syndrome; or medical therapy alone). Patients (approximately N = 1,038) will be randomly assigned at a 1:1 ratio to (1) monotherapy with edoxaban (a non-vitamin K antagonist oral anticoagulant) or (2) combination therapy with edoxaban plus a single antiplatelet agent. The primary endpoint is the net composite outcome of death from any cause, stroke, systemic embolism, myocardial infarction, unplanned revascularization, and major or clinically relevant nonmajor bleeding at 1 year after randomization. RESULTS: As of December 2021, approximately 901 patients had been randomly enrolled over 2 years at 18 major cardiac centers across South Korea. The completed enrollment is expected at the mid-term of 2022, and the primary results will be available by 2023. CONCLUSIONS: EPIC-CAD is a large-scale, multicenter, pragmatic design trial, which will provide valuable clinical insight into edoxaban-based long-term antithrombotic therapy in patients with high-risk AF and stable CAD.

Gender Differences in the Impact of New-Onset Atrial Fibrillation on Long-Term Risk of Ischemic Stroke after Acute Myocardial Infarction.

BACKGROUND: Atrial fibrillation (AF) has been identified as a major risk factor for mortality after acute coronary syndrome (ACS). However, the long-term risk of ischemic stroke associated with new-onset atrial fibrillation (NOAF) in ACS remains controversial, and its gender-specific association is unknown. METHODS: We analyzed the data of 10,137 ACS survivors included in a multicenter, prospective registry for Korean patients with acute myocardial infarction (AMI) between January 2004 and August 2014. Subjects were categorized into three groups (non-AF vs. NOAF vs. previous AF) based on medical history and electrocardiographic evidence of AF, either at admission or during hospitalization. RESULTS: Among the total study population (72.3% men), 370 patients (3.6%) had NOAF and 130 (1.3%) had previous AF. During a median follow-up of 61 months (interquartile range, 38.8 to 89.3 months), 245 (2.4%) patients (218 (2.3%) non-AF vs. 15 (4.1%) NOAF vs. 12 (9.2%) previous AF, p < 0.001) experienced ischemic stroke. After adjustment for confounding variables, both NOAF (adjusted hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.09-3.24, p = 0.024) and previous AF (adjusted HR 4.00, 95% CI 2.03-7.87, p < 0.001), along with older age, diabetes, current smoker, and previous stroke were independent risk factors of ischemic stroke. In the gender-stratified analysis, men with previous AF but not NOAF had a significantly higher risk of ischemic stroke (adjusted HR 4.14, 95% CI 1.79-9.55, p = 0.001) than those without AF. In women, NOAF (adjusted HR 2.54, 95% CI 1.21-5.35, p = 0.014) as well as previous AF (adjusted HR 3.72, 95% CI 1.16-11.96, p = 0.028) was a strong predictor of ischemic stroke, and the predictive value was comparable to that of previous AF among patients with a CHA2DS2-VASc score ≥ 2. CONCLUSIONS: Both NOAF and previous AF were associated with ischemic stroke after AMI, but the impact of NOAF as a risk factor of ischemic stroke was significant only in women.

Efficacy and safety of co-administered telmisartan/amlodipine and rosuvastatin in subjects with hypertension and dyslipidemia.

Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low-density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow-up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least-Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were -19.3 (2.68) mm Hg and -6.69 (2.76) mm Hg. The difference between the two groups was significant (-12.60 (2.77) mm Hg, 95% CI -18.06 to -7.14, P < .0001). The LS Mean for the percent changes from baseline in LDL cholesterol in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg) groups were -52.45 (3.23) % and 2.68 (3.15) %. The difference between the two groups was significant (-55.13 (3.20) %, 95% CI -61.45 to -48.81, P < .0001). There were no adverse events leading to discontinuation or death. Combined administration of telmisartan/amlodipine 80/5 mg and rosuvastatin 20 mg for the treatment of hypertensive patients with dyslipidemia significantly reduces blood pressure and improves lipid control. ClinicalTrials.gov identifier: NCT03067688.

Safety and Efficacy of Pitavastatin in Patients With Impaired Fasting Glucose and Hyperlipidemia: A Randomized, Open-labeled, Multicentered, Phase IV Study.

PURPOSE: Although the role of high-intensity lipid-lowering therapy in cardiovascular protection has broadened, concerns still exist about new-onset diabetes mellitus (NODM), especially in vulnerable patients. This study aimed to compare the effect of high-dose (4 mg/d) and usual dose (2 mg/d) pitavastatin on glucose metabolism in patients with hyperlipidemia and impaired fasting glucose (IFG). METHODS: In this 12-month study, glucose tolerance and lipid-lowering efficacy of high-dose pitavastatin (4 mg [study group]) was compared with that of usual dose pitavastatin (2 mg [control group]) in patients with hyperlipidemia and IFG. The primary end point was the change of glycosylated hemoglobin (HbA1c) after 24 weeks of treatment. The secondary end points were as follows: (1) NODM within 1 year after treatment, (2) change of lipid parameters, (3) changes of adiponectin, and (4) change of blood glucose and insulin levels. FINDINGS: Of the total 417 patients screened, 313 patients with hypercholesterolemia and IFG were randomly assigned into groups. The mean (SD) change in HbA1c was 0.06% (0.20%) in the study group and 0.03% (0.22%) in the control group (P = 0.27). Within 1 year, 27 patients (12.3%) developed NODM, including 12 (10.6%) of 113 patients in the study group and 15 (14.2%) of 106 in the control group (P = 0.43). The study group had a significantly higher reduction of total cholesterol and LDL-C levels and a higher increase in apolipoprotein A1/apolipoprotein B ratio (0.68 [0.40] vs 0.51 [0.35], P < 0.01). IMPLICATIONS: The high-dose pitavastatin therapy did not aggravate glucose metabolism compared with the usual dose therapy. Moreover, it had a better effect on cholesterol-lowering and apolipoprotein distribution in the patients with hyperlipidemia and IFG.

The impact of educational attainment on cardiorespiratory fitness and metabolic syndrome in Korean adults.

The aim of this study was to evaluate the relationship between educational attainment and cardiorespiratory fitness (CRF) as a predictor of metabolic syndrome in a Korean population.In this single-center, retrospective cross-sectional study, 988 healthy adults (601 men and 387 women) who underwent regular health check-up in Seoul St. Mary's Hospital were analyzed. Educational attainment was categorized into 3 groups according to their final grade of educational course: middle or high school (≤12 years of education), college or university (12-16 years of education), and postgraduate (≥16 years of education). CRF was assessed by cardiopulmonary exercise testing, biceps strength, hand grip strength, bioelectrical impedance analysis, and echocardiography. Metabolic syndrome was diagnosed according to the 3rd report of the National Cholesterol Education Program.Among the subjects, 357 (36.1%) had metabolic syndrome. The postgraduate group had significantly higher peak oxygen consumption (VO2), biceps strength, hand grip strength, and peak expiratory flow than other groups (all P < .001). This group showed better left ventricular diastolic function, in terms of deceleration time of mitral inflow, maximal tricuspid valve regurgitation velocity, and left atrial volume index than other groups. Peak VO2 (%) was significantly correlated with all the parameters of metabolic syndrome, including insulin resistance (r = -0.106, P = .002), waist circumference (r = -0.387, P < .001), triglyceride (r = -0.109, P = .001), high density lipoprotein-cholesterol (r = 0.219, P < .001), systolic blood pressure (r = -0.143, P < .001), and diastolic blood pressure (r = -0.177, P < .001). And Peak VO2 (%) was found to be a predictor of metabolic syndrome (adjusted ß = .988, P < .001). However, the level of education was not able to predict metabolic syndrome (postgraduate group; ß = .955, P = .801).Although the postgraduate group had better CRF than other groups, the educational attainment could not exclusively predict metabolic syndrome in this study. Further research is needed to reveal the socioeconomic mechanism of developing metabolic syndrome.

Comparison of successful percutaneous coronary intervention versus optimal medical therapy in patients with coronary chronic total occlusion.

BACKGROUND: Chronic total occlusion (CTO) is a challenging entity in coronary interventions. With improvements in technology and techniques, success rates for percutaneous coronary intervention (PCI) of CTO continue to improve. However, the clinical benefits of PCI remain unclear. The aim of the study was to determine the effectiveness of successful PCI on clinical outcomes using drug-eluting stents in patients with CTO. METHODS: From 2004 to 2010, we analyzed 898 patients with at least one CTO who underwent successful PCI (n=424, 448 lesions) or only medical treatment (n=474, 519 lesions) from a multicenter registry. The primary outcome was all-cause death. RESULTS: During a median of 2.2 years, incidence rate of all-cause death after successful PCI was lower than that after medical treatment (10.6% and 17.5%, p=0.004). However, the multivariate Cox proportional hazards model showed that successful PCI was not associated with improvement in mortality compared to medical treatment [adjusted hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.57-1.24, p=0.38]. Comparable results were obtained after propensity-score matching. Subgroup analysis of propensity-score matched population demonstrated that patients with age under 65 years benefited from successful PCI (HR 0.25, 95% CI 0.08-0.75, p for interaction=0.005). CONCLUSIONS: In patients considered for CTO intervention, medical treatment appears to be associated with a similar mortality compared to successful PCI. Successful CTO PCI might be associated with survival benefit in younger patients compared to medical treatment.

Thyroid stimulating hormone elevation as a predictor of long-term mortality in patients with acute myocardial infarction.

BACKGROUND: Hypothyroidism has been known to be associated with hyperlipidemia, endothelial dysfunction and atherosclerosis. Elevation of thyroid-stimulation hormone (TSH) is a gold standard to detect these conditions. However, no large studies have investigated the association between TSH elevation and long-term clinical outcomes in patients with acute myocardial infarction (AMI). HYPOTHESIS: Hypothyroidism is associated with higher mortality in patients with AMI. METHODS: A total of 4748 AMI patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents were consecutively enrolled. We analyzed 1977 patients whose thyroid function data available after the exclusion of hyperthyroidism and possible central hypothyroidism. Patients were divided into two groups; euthyroid group (n = 1846) with normal TSH and normal free thyroxine (FT4); hypothyroidism group (n = 131) with elevated TSH and normal or low FT4. The two groups were subsequently compared with their all-cause and cardiac mortalities. RESULTS: Median follow-up duration was 3.5 years. Hypothyroidism group were older, included in more females, and had higher incidences of atrial fibrillation, stroke, and renal dysfunction. Elevated TSH was associated with significantly higher all-cause mortality (26.0% vs 11.7%, P < 0.0001) and cardiac mortality (9.2% vs 4.6%, P = 0.014). The multivariate Cox proportional hazards model identified that TSH elevation was a significant predictor of all-cause mortality (adjusted hazard ratio 1.560, 95% confidence interval 1.017 to 2.392, P = 0.041). CONCLUSIONS: Our data suggest that AMI patients with TSH elevation had worse clinical outcome. Moreover, TSH elevation was a predictor of all-cause mortality in patients with AMI.

Differential Impact of Chronic Kidney Disease on Coronary Calcification and Atherosclerosis in Asymptomatic Individuals with or without Diabetes: Analysis from a Coronary Computed Tomographic Angiography Registry.

AIM: The aim of this study was to assess the combined effects of chronic kidney disease (CKD) and diabetes on the extent and developmental pattern of coronary artery disease (CAD). METHODS: A total of 3,017 self-referred asymptomatic individuals without known CAD who underwent 64-channel dual-source coronary computed tomography angiography between 2006 and 2010 were enrolled. The patients were divided into six groups based on their diabetes status (nondiabetic or diabetic) and estimated glomerular filtration rate (eGFR) (eGFR > 90 mL/min/1.73 m2, normal renal function; eGFR 60-89, mild CKD; or eGFR 30-59, moderate CKD). We compared the coronary artery calcium score (CACS), segment stenosis score (SSS), and ≥50% obstructive CAD among the groups. RESULTS: In nondiabetics, whereas SSS and ≥50% obstructive CAD were not different as renal function deteriorated, after adjusting for cardiovascular risk factors, CACS showed a unique developmental pattern: no CACS increase until mild CKD, but abrupt increase from the stage of moderate CKD (moderate vs. normal renal function, adjusted OR 5.118, 95% CI 1.293-20.262, p = 0.020). In diabetics, patients from the stage of mild CKD were more likely to have ≥50% obstructive CAD (p = 0.004), higher CACS (p = 0.020), and SSS (p = 0.001) in multivariable analysis. CONCLUSIONS: The presence of CKD did not have a significant impact on the development of coronary atherosclerosis, but affected the progression of coronary calcification more markedly from the stage of moderate CKD in nondiabetics. However, in diabetics, the deterioration of renal function was significantly associated with the development of coronary atherosclerosis and calcification from the stage of mild CKD.

Clinical and Angiographic Outcomes of the First Korean-made Sirolimus-Eluting Coronary Stent with Abluminal Bioresorbable Polymer.

BACKGROUND AND OBJECTIVES: This trial evaluated the safety and efficacy of the Genoss drug-eluting coronary stent. METHODS: This study was a prospective, multicenter, randomized trial with a 1:1 ratio of Genoss drug-eluting stent (DES)™ and Promus Element™. Inclusion criteria were the presence of stable angina, unstable angina, or silent ischemia. Angiographic inclusion criteria were de novo coronary stenotic lesion with diameter stenosis >50%, reference vessel diameter of 2.5-4.0 mm, and lesion length ≤40 mm. The primary endpoint was in-stent late lumen loss at 9-month quantitative coronary angiography follow-up. Secondary endpoints were in-segment late lumen loss, binary restenosis rate, death, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis during 9 months of follow-up. RESULTS: We enrolled 38 patients for the Genoss DES™ group and 39 patients for the Promus Element™ group. In-stent late lumen loss at 9 months was not significantly different between the 2 groups (0.11±0.25 vs. 0.16±0.43 mm, p=0.567). There was no MI or stent thrombosis in either group. The rates of death (2.6% vs. 0%, p=0.494), TLR (2.6% vs. 2.6%, p=1.000), and TVR (7.9% vs. 2.6%, p=0.358) at 9 months were not significantly different. CONCLUSION: This first-in-patient study of the Genoss DES™ stent showed excellent angiographic outcomes for in-stent late lumen loss and major adverse cardiac events over a 9-month follow-up.

Computed Tomography Angiography Images of Coronary Artery Stenosis Provide a Better Prediction of Risk Than Traditional Risk Factors in Asymptomatic Individuals With Type 2 Diabetes: A Long-term Study of Clinical Outcomes.

OBJECTIVE: We investigated the efficacy of coronary computed tomography angiography (CCTA) in predicting the long-term risks in asymptomatic patients with type 2 diabetes and compared it with traditional risk factors. RESEARCH DESIGN AND METHODS: We analyzed 933 patients with asymptomatic type 2 diabetes who underwent CCTA. Stenosis was considered obstructive (≥50%) in each coronary artery segment using CCTA. The extent and severity scores for coronary artery disease (CAD) were evaluated. The primary end point was major adverse cardiovascular events (MACE), including all-cause mortality, nonfatal myocardial infarction, and late coronary revascularization during a mean follow-up period of 5.5 ± 2.1 years. RESULTS: Ninety-four patients with MACE exhibited obstructive CAD with a greater extent and higher severity scores (P < 0.001 for all). After adjusting for confounding risk factors, obstructive CAD remained an independent predictor of MACE (hazard ratio 3.11 [95% CI 2.00-4.86]; P < 0.001]). The performance of a risk prediction model based on C-statistics was significantly improved (C-index 0.788 [95% CI 0.747-0.829]; P = 0.0349) upon the addition of a finding of obstructive CAD using CCTA to traditional risk factors, including age, male, hypertension, hyperlipidemia, smoking, estimated glomerular filtration rate, and HbA1c. Both integrated discrimination improvement (IDI) and net reclassification improvement (NRI) analyses further supported this finding (IDI 0.046 [95% CI 0.020-0.072], P < 0.001, and NRI 0.55 [95% CI 0.343-0.757], P < 0.001). In contrast, the risk prediction power of the coronary artery calcium score remained unimproved (C-index 0.740, P = 0.547). CONCLUSIONS: Based on our data, the addition of CCTA-detected obstructive CAD to models that include traditional risk factors improves the predictions of MACE in asymptomatic patients with type 2 diabetes.

3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair.

Stem cell therapy is a promising therapeutic method for the treatment of ischemic heart diseases; however, some challenges prohibit the efficacy after cell delivery due to hostile microenvironment of the injured myocardium. 3D printed pre-vascularized stem cell patch can enhance the therapeutic efficacy for cardiac repair through promotion of rapid vascularization after patch transplantation. In this study, stem cell-laden decellularized extracellular matrix bioinks are used in 3D printing of pre-vascularized and functional multi-material structures. The printed structure composed of spatial patterning of dual stem cells improves cell-to-cell interactions and differentiation capability and promotes functionality for tissue regeneration. The developed stem cell patch promoted strong vascularization and tissue matrix formation in vivo. The patterned patch exhibited enhanced cardiac functions, reduced cardiac hypertrophy and fibrosis, increased migration from patch to the infarct area, neo-muscle and capillary formation along with improvements in cardiac functions. Therefore, pre-vascularized stem cell patch provides cardiac niche-like microenvironment, resulting in beneficial effects on cardiac repair.

HDL Cholesterol Level Is Associated with Contrast Induced Acute Kidney Injury in Chronic Kidney Disease Patients Undergoing PCI.

Chronic kidney disease (CKD) is a significant risk factor for contrast induced acute kidney injury (CI-AKI) after percutaneous coronary intervention (PCI). This study included 1592 CKD patients extracted from a prospective multicenter, all comer-based registry of patients undergoing PCI. In multivariate logistic analysis for CI-AKI development, a significant linear trend was observed between the quartiles of HDL-C (quartile 1 vs. 2: odds ratio [OR], 0.716; 95% confidence interval [CI], 0.421-1.219; quartile 1 vs. 3: OR, 0.534; 95% CI, 0.301-0.947; quartile 1 vs. 4: OR, 0.173; 95% CI, 0.079-0.377; P for trend < 0.001). HDL-C quartiles were also negatively correlated with the incidence of CI-AKI; 19.0%, 12.1%, 8.7%, and 3.7% for quartile 1(Q1) (<34 mg/dL), Q2 (34-40 mg/dL), Q3 (40-48 mg/dL), and Q4 (>48 mg/dL) respectively (P < 0.001 overall and for the trend). Multivariate Cox regression analysis for the long term mortality, the highest HDL-C quartile was associated with decreased mortality compared with the lowest HDL-C quartile (hazard ratio [HR] 0.516, 95% CI, 0.320-0.832, P = 0.007). Our study suggests more intensive strategies should be considered for preventing CI-AKI in CKD patients with low serum HDL-C level who is planned for PCI.

Impact of Cardiorenal Anemia Syndrome on Short- and Long-Term Clinical Outcomes in Patients Hospitalized with Heart Failure.

BACKGROUND: Dysfunctional interplay between the heart and kidneys may lead to the development of anemia. The aim of this study was to evaluate the impact of cardiorenal anemia syndrome (CRAS) on short- and long-term outcomes among patients hospitalized with heart failure (HF). METHODS: We enrolled 303 patients hospitalized with HF. We divided the patients into two groups: a CRAS group (n = 64) and a non-CRAS group (n = 239). We defined CRAS as HF accompanied by (1) an estimated glomerular filtration rate <60 ml/min/1.73 m(2) calculated by the Modification of Diet in Renal Disease at admission and (2) a hemoglobin level <12 g/dl for females and <13 g/dl for males at admission. The primary outcome was a composite of cardiac death, non-fatal myocardial infarction and rehospitalization for HF. RESULTS: During a median follow-up period of 25.6 months (range 0.1-35.3 months), the patients with CRAS had a significantly increased risk for the primary outcome (27.5 vs. 10.7%, p < 0.001) compared with the patients in the non-CRAS group. Using Cox proportional hazard analyses, the hazard ratio (HR) for the presence of CRAS was found to be 1.874 (95% confidence interval [CI] 1.011-3.475, p = 0.046); HRs were also computed for the presence of diabetes mellitus (HR = 2.241, 95% CI 1.221-4.112, p = 0.009), New York Heart Association class III or IV HF (HR = 2.948, 95% CI 1.206-7.205, p = 0.018) and the use of intravenous loop diuretics (HR = 2.286, 95% CI 0.926-5.641, p = 0.073). CONCLUSIONS: Renal dysfunction and anemia are a fatal combination and are associated with poor prognosis in patients with HF.

Sirolimus-eluting stent is superior to paclitaxel-eluting stent for coronary intervention in patients with renal insufficiency: Long-term clinical outcomes.

BACKGROUND: Renal insufficiency (RI) is an independent risk factor for the adverse cardiovascular events. Long-term clinical outcome of percutaneous coronary intervention (PCI) in patients with RI is unknown especially in the era of first generation drug-eluting stents (DES). This study aims at comparing clinical outcomes between sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) based on large scaled registry. METHODS: Patients who underwent PCI with DES from January 2004 to December 2009 in the Catholic University of Korea-PCI (COACT) registry were prospectively enrolled. A group of 1,033 patients with RI, defined as estimated glomerular filtration rate under 60 mL/min, were analyzed. Major adverse cardiac events (MACE), including all-cause death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR) according to the type of stents were compared. RESULTS: Median follow-up period was 810 days (interquartile range: from 361 to 1,354 days). A group of 612 (59.2%) patients were treated with SES and 421 (40.8%) patients were treated with PES. The PES vs. SES group had significantly higher rate of MACE (35.9% vs. 28.3%, p = 0.01). In multivariate Cox hazard regression analysis, PES vs. SES group had significantly higher rate of MACE (adjusted hazard ratio [AHR] 1.29, 95% confidence interval [CI] 1.02-1.64, p = 0.033), particularly pronounced by all-cause death (AHR 1.34, 95% CI 1.008-1.770; p = 0.044). In further analysis with propensity score matching, overall findings were consistent. CONCLUSIONS: In patients with RI, PCI using PES provides poorer clinical outcomes than SES in terms of MACE and all-cause death.

CYP2C19 loss-of-function alleles are not associated with clinical outcome of clopidogrel therapy in patients treated with newer-generation drug-eluting stents.

CYP2C19 loss-of-function (LOF) alleles adversely affect clinical outcome of clopidogrel therapy. Recent introduction of a newer-generation drug-eluting stent (DES) has significantly reduced the occurrence of stent thrombosis.The aim of this study was to evaluate the impact of CYP2C19 LOF alleles on clinical outcome in patients treated with the newer-generation DES.The effects of CYP2C19 genotypes were evaluated on clinical outcome of clopidogrel therapy in 2062 patients treated with percutaneous coronary intervention using either first-generation DES (sirolimus- and paclitaxel-eluting stent, n = 1349) or newer-generation DES (everolimus- and zotarolimus-eluting stent, n = 713). The primary clinical outcome was major cardiac and cerebrovascular event (MACCE) including cardiac death, nonfatal myocardial infarction, stroke, and stent thrombosis during 1 year of follow-up.CYP2C19 LOF alleles were significantly associated with a higher risk of MACCE in patients treated with first-generation DES (hazard ratio [HR] 2.599, 95% confidence interval [CI] 1.047-6.453; P = 0.034). In contrast, CYP2C19 LOF alleles were not associated with primary outcome in newer-generation DES (HR 0.716, 95% CI 0.316-1.622; P = 0.522). In the further multivariate analysis, CYP2C19 LOF alleles were not associated with MACCE in patients receiving newer-generation DES (adjusted HR 0.540, 95% CI 0.226-1.291; P = 0.166), whereas they were demonstrated to be an independent risk factor for MACCE in those implanted with first-generation DES (adjusted HR 3.501, 95% CI 1.194-10.262; P = 0.022).In contradiction to their clinical impact in first-generation DES era, CYP2C19 LOF alleles may not affect clinical outcome of clopidogrel therapy in patients treated with newer-generation DES.

Incidence, Implications, and Predictors of Stent Thrombosis in Acute Myocardial Infarction.

Stent thrombosis (ST) remains a catastrophic problem in patients undergoing percutaneous coronary intervention (PCI). However, a paucity of data exist regarding the incidence, implications, and predictors of ST in patients with acute myocardial infarction (AMI). We consecutively enrolled patients with AMI in the CardiOvascular Risk and idEntificAtion of potential high-risk population in AMI registry who underwent PCI from January 2004 to December 2009 and analyzed definite or probable ST according to Academic Research Consortium definitions. The median follow-up duration was 41.9 months. Definite or probable ST occurred in 136 patients (3.7%), including 44 with early ST (1.0%), 38 with late ST (0.9%), and 54 with very late ST (2.0%). The annual incidence of very late ST ranged from 0.5% to 0.6%. The all-cause mortality rate after ST was 29%, which was higher than that for patients without ST (17%; p <0.001). The independent predictors of ST were no-reflow phenomenon (hazard ratio [HR] 1.96, 95% confidence interval [CI] 1.28 to 3.03), decreased left ventricular ejection fraction (HR 1.70, 95% CI 1.21 to 2.40), anemia (HR 1.54, 95% CI 1.09 to 2.18), and a mean stent diameter <3.0 mm (HR 1.53, 95% CI 1.04 to 2.27). ST is not uncommon in patients with AMI and continues to occur beyond 1 year after PCI, irrespective of the stent type or clinical presentation. Patients with ST are associated with higher mortality than patients without ST. No reflow, decreased left ventricular ejection fraction, anemia, and a mean stent diameter <3.0 mm are independent predictors of ST.

Association between the Red Cell Distribution Width and Vasospastic Angina in Korean Patients.

PURPOSE: The association between the red cell distribution width (RDW) and vasospastic angina (VSA) has not been elucidated. We investigated the association of the RDW with the incidence and angiographic subtypes of VSA in Korean patients. MATERIALS AND METHODS: A total of 460 patients who underwent intracoronary ergonovine provocation tests were consecutively enrolled and classified into two groups: the VSA group (n=147, 32.0%) and non-VSA group (n=313, 68.0%). The subjects were classified into 3 subgroups (tertiles) according to the baseline level of RDW assessed before the angiographic provocation test. RESULTS: The VSA group had a higher RDW than the non-VSA group (12.9±0.8% vs. 12.5±0.7%, p=0.013). The high RDW level demonstrated an independent association with the high incidence of VSA [second tertile: hazard ratio (HR) 1.96 (1.13-2.83), third tertile: HR 2.33 (1.22-3.47), all p<0.001]. Moreover, the highest RDW tertile level had a significant association with the prevalence of the mixed-type coronary spasm [HR 1.29 (1.03-1.59), p=0.037]. CONCLUSION: The high level of RDW was significantly associated with the prevalence of VSA and the high-risk angiographic subtype of coronary spasm, suggesting that a proactive clinical investigation for VSA could be valuable in Korean patients with an elevated RDW.

Impact of Percutaneous Coronary Intervention for Chronic Total Occlusion in Non-Infarct-Related Arteries in Patients With Acute Myocardial Infarction (from the COREA-AMI Registry).

Chronic total occlusion (CTO) in a non-infarct-related artery (IRA) is an independent predictor of clinical outcomes in patients with acute myocardial infarction (AMI). This study evaluated the impact of successful percutaneous coronary intervention (PCI) for CTO of a non-IRA on the long-term clinical outcomes in patients with AMI. A total of 4,748 patients with AMI were consecutively enrolled in the Convergent Registry of Catholic and Chonnam University for AMI registry from January 2004 to December 2009. We enrolled 324 patients with CTO in a non-IRA. To adjust for baseline differences, propensity matching (96 matched pairs) was used to compare successful PCI and occluded CTO for the treatment of CTO in non-IRA. The primary clinical end points were all-cause mortality and a composite of the major adverse cardiac events, including cardiac death, MI, stroke, and any revascularization during the 5-year follow-up. Patients who received successful PCI for CTO of non-IRA had lower rates of all-cause mortality (16.7% vs 32.3%, hazard ratio 0.459, 95% CI 0.251 to 0.841, p = 0.012) and major adverse cardiac events (21.9% vs 55.2%, hazard ratio 0.311, 95% CI 0.187 to 0.516, p <0.001) compared with occluded CTO group. Subgroup analyses revealed that successful PCI resulted in a better mortality rate in patients with normal renal function compared to patients with chronic kidney disease (p = 0.010). In conclusion, successful PCI for CTO of non-IRA is associated with improved long-term clinical outcomes in patients with AMI.

Oncogenic potential of histone-variant H2A.Z.1 and its regulatory role in cell cycle and epithelial-mesenchymal transition in liver cancer.

H2A.Z is a highly conserved H2A variant, and two distinct H2A.Z isoforms, H2A.Z.1 and H2A.Z.2, have been identified as products of two non-allelic genes, H2AFZ and H2AFV. H2A.Z has been reported to be overexpressed in breast, prostate and bladder cancers, but most studies did not clearly distinguish between isoforms. One recent study reported a unique role for the H2A.Z isoform H2A.Z.2 as a driver of malignant melanoma. Here we first report that H2A.Z.1 plays a pivotal role in the liver tumorigenesis by selectively regulating key molecules in cell cycle and epithelial-mesenchymal transition (EMT). H2AFZ expression was significantly overexpressed in a large cohort of hepatocellular carcinoma (HCC) patients, and high expression of H2AFZ was significantly associated with their poor prognosis. H2A.Z.1 overexpression was demonstrated in a subset of human HCC and cell lines. H2A.Z.1 knockdown suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins and caused apoptotic cell death of HCC cells. We also observed that H2A.Z.1 knockdown reduced the metastatic potential of HCC cells by selectively modulating epithelial-mesenchymal transition regulatory proteins such as E-cadherin and fibronectin. In addition, H2A.Z.1 knockdown reduced the in vivo tumor growth rate in a mouse xenograft model. In conclusion, our findings suggest the oncogenic potential of H2A.Z.1 in liver tumorigenesis and that it plays established role in accelerating cell cycle transition and EMT during hepatocarcinogenesis. This makes H2A.Z.1 a promising target in liver cancer therapy.