Effect of hemoglobin A1c change on 24-month clinical outcomes in patients with diabetes after acute myocardial infarction.

BACKGROUND: The average glycated hemoglobin (HbA1c) may not accurately reflect glycemic control status during the mid-term after acute myocardial infarction (AMI). We aimed to evaluate changes in HbA1c and their effect on mid-term clinical outcomes in patients with diabetes and AMI. METHODS: We enrolled patients with diabetes (n = 967) who underwent HbA1c measurement in the Korean nationwide registry. These patients were categorized into three groups based on changes in HbA1c from index admission to the 1-year follow-up visit: a decrease in HbA1c > 1%, changes in HbA1c within 1%, and an increase in HbA1c > 1%. Clinical outcomes at 24 months were examined. RESULTS: The baseline HbA1c levels were 8.55 ±â€…0.85, 7.00 ±â€…0.98 and 7.07 ±â€…1.05 (P = 0.001) and HbA1c levels after 1 year were 6.62 ±â€…0.73, 7.05 ±â€…0.98 and 9.26 ±â€…1.59 (P = 0.001) for patients with 3 groups, respectively. Patients with a 1% decrease in HbA1c had significantly lower incidence of major adverse cardiovascular events (MACE), cardiac death, and rehospitalization after 24 months than those with a 1% increase in HbA1c. However, in the Cox regression analysis, a >1% decrease in HbA1c change was not an independent factor for MACE, cardiac death, and rehospitalization. CONCLUSIONS: Our analysis indicates that an HbA1c decrease of >1% within the first 12 months was not an independent prognostic factor until the 24-month mark. Therefore, standard diabetic control is recommended for patients with diabetes and AMI for up to 2 years.

Everolimus-Eluting Stents or Bypass Surgery for Multivessel Disease in Diabetics: The BEST Extended Follow-Up Study.

BACKGROUND: Diabetes mellitus is associated with more complex coronary artery diseases. Coronary artery bypass grafting (CABG) is a preferred revascularization strategy over percutaneous coronary intervention (PCI) in diabetics with multivessel coronary artery disease (MVD). OBJECTIVES: This study sought to examine the different prognostic effects of revascularization strategies according to the diabetes status from the randomized BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) trial. METHODS: Patients (n = 880) with MVD were randomly assigned to undergo PCI with an everolimus-eluting stent vs CABG stratified by diabetics (n = 363) and nondiabetics (n = 517). The primary endpoint was the composite of death, myocardial infarction, or target vessel revascularization during a median follow-up of 11.8 years (IQR: 10.6-12.5 years). RESULTS: In diabetics, the primary endpoint rate was significantly higher in the PCI group than in the CABG group (43% and 32%; HR: 1.53; 95% CI: 1.12-2.08; P = 0.008). However, in nondiabetics, no significant difference was found between the groups (PCI group, 29%; CABG group, 29%; HR: 0.97; 95% CI: 0.67-1.39; P = 0.86; Pinteraction= 0.009). Irrespective of the presence of diabetes, no significant between-group differences were found in the rate of a safety composite of death, myocardial infarction, or stroke and mortality rate. However, the rate of any repeat revascularization was significantly higher in the PCI group than in the CABG group. CONCLUSIONS: In diabetics with MVD, CABG was associated with better clinical outcomes than PCI. However, the mortality rate was similar between PCI and CABG irrespective of diabetes status during an extended follow-up. (Ten-Year Outcomes of Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST Extended], NCT05125367; Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST], NCT00997828).

Comparison of efficacy and safety between third-dose triple and third-dose dual antihypertensive combination therapies in patients with hypertension.

We compared the efficacy and safety of third-standard-dose triple and third-standard-dose dual antihypertensive combination therapies in patients with mild to moderate hypertension. This was a phase II multicenter, randomized, double-blind, parallel-group trial. After a 4-week placebo run-in period, 245 participants were randomized to the third-dose triple combination (ALC group; amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg) or third-dose dual combination (AL group; amlodipine 1.67 mg + losartan potassium 16.67 mg, LC group; losartan potassium 16.67 mg + chlorthalidone 4.17 mg, AC group; amlodipine 1.67 mg + chlorthalidone 4.17 mg) therapy groups and followed up for 8 weeks. The mean systolic blood pressure (BP) reduction was -18.3 ± 13.2, -13.0 ± 13.3, -16.3 ± 12.4, and -13.8 ± 13.2 mmHg in the ALC, AL, LC, and AC groups, respectively. The ALC group showed significant systolic BP reduction compared to the AL and AC groups at weeks 4 (P = .010 and P = .018, respectively) and 8 (P = .017 and P = .036, respectively). At week 4, the proportion of systolic BP responders was significantly higher in the ALC group (42.6%) than in the AL (22.0%), LC (23.3%), and AC (27.1%) groups (P = .013, P = .021, and P = .045, respectively). At week 8, the proportion of systolic and diastolic BP responders was significantly higher in the ALC group (59.7%) than in the AL (39.3%) and AC (42.4%) groups (P = .022 and P = .049, respectively) at week 8. Third-standard-dose triple antihypertensive combination therapy demonstrated early effective BP control compared to third-standard-dose dual combination therapies, without increasing adverse drug reactions in patients with mild-to-moderate hypertension.

Triple Antiplatelet Therapy with Cilostazol and Favorable Early Clinical Outcomes after Acute Myocardial Infarction Compared to Dual Antiplatelet Therapy with Standard or Potent P2Y12 Inhibitors.

Current guidelines for the management of acute myocardial infarction (AMI) recommend potent P2Y12 inhibitors rather than clopidogrel to prevent ischemic events. However, their ischemic benefits are offset by an increased major bleeding risk. We compared the efficacy and safety of triple antiplatelet therapy with cilostazol in the first month after AMI. This study investigated 16,643 AMI patients who received percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in nationwide, real-world, multicenter registries in Korea. Patients were divided into DAPT (aspirin and clopidogrel, n = 11,285), Triple (aspirin, clopidogrel and cilostazol, n = 2547), and Potent (aspirin and ticagrelor/prasugrel, n = 2811) groups. The primary outcomes were net adverse clinical events (NACE), a composite of death from any cause, myocardial infarction (MI), stroke, and TIMI major bleeding one month after AMI. After adjusting for covariates, there were no statistically significant differences in the risk of death from any cause, MI, or stroke between the three groups. However, the risk of TIMI major bleeding was significantly greater in the Potent group than in the DAPT and Triple groups (p < 0.001). Accordingly, NACE was significantly higher in the DAPT (HR 1.265; 95% CI 1.006−1.591, p = 0.044) and Potent groups (HR 1.515; 95% CI 1.142−2.011, p = 0.004) than in the Triple group. Triple antiplatelet therapy with cilostazol was associated with an improved net clinical outcome in the first month after AMI without increasing the risk of bleeding compared to potent or standard P2Y12 inhibitor-based DAPT.

Everolimus-Eluting Stents or Bypass Surgery for Multivessel Coronary Artery Disease: Extended Follow-Up Outcomes of Multicenter Randomized Controlled BEST Trial.

BACKGROUND: Long-term comparative outcomes after percutaneous coronary intervention (PCI) with everolimus-eluting stents and coronary artery bypass grafting (CABG) are limited in patients with multivessel coronary artery disease. METHODS: This prospective, multicenter, randomized controlled trial was conducted in 27 international heart centers and was designed to randomly assign 1776 patients with angiographic multivessel coronary artery disease to receive PCI with everolimus-eluting stents or CABG. After inclusion of 880 patients (438 in the PCI group and 442 in the CABG group) between July 2008 and September 2013, the study was terminated early because of slow enrollment. The primary end point was the composite of death from any cause, myocardial infarction, or target vessel revascularization. RESULTS: During a median follow-up of 11.8 years (interquartile range, 10.6-12.5 years; maximum, 13.7 years), the primary end point occurred in 151 patients (34.5%) in the PCI group and 134 patients (30.3%) in the CABG group (hazard ratio [HR], 1.18 [95% CI, 0.88-1.56]; P=0.26). No significant differences were seen in the occurrence of a safety composite of death, myocardial infarction, or stroke between groups (28.8% and 27.1%; HR, 1.07 [95% CI, 0.75-1.53]; P=0.70), as well as the occurrence of death from any cause (20.5% and 19.9%; HR, 1.04 [95% CI, 0.65-1.67]; P=0.86). However, spontaneous myocardial infarction (7.1% and 3.8%; HR, 1.86 [95% CI, 1.06-3.27]; P=0.031) and any repeat revascularization (22.6% and 12.7%; HR, 1.92 [95% CI, 1.58-2.32]; P<0.001) were more frequent after PCI than after CABG. CONCLUSIONS: In patients with multivessel coronary artery disease, there were no significant differences between PCI and CABG in the incidence of major adverse cardiac events, the safety composite end point, and all-cause mortality during the extended follow-up. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT05125367 and NCT00997828.

Monotherapy versus combination therapy of statin and renin-angiotensin system inhibitor in ST-segment elevation myocardial infarction.

BACKGROUND: The beneficial effects of statin and renin-angiotensin system inhibitor (RASI) are well-known. In this retrospective cohort study, 2-year clinical outcomes were compared between monotherapy and combination therapy with statin and RASI in ST-segment elevation myocardial infarction (STEMI) patients after stent implantation. METHODS: A total of 17,414 STEMI patients were enrolled and divided into the three groups (group A: 2448 patients, statin alone; group B: 2431 patients, RASI alone; and group C: 12,535 patients, both statin and RASI). The principal clinical endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction, and any repeat revascularization. RESULTS: After adjustment, the cumulative incidences of MACEs in group A (adjusted hazard ratio [aHR] 1.337; 95% confidence interval [CI] 1.064-1.679; p = 0.013) and in group B (aHR 1.375; 95% CI 1.149-1.646; p = 0.001) were significantly higher than in group C. The cumulative incidence of all-cause death in group A was significantly higher than that in group C (aHR 1.539; 95% CI 1.014-2.336; p = 0.043). The cumulative incidences of any repeat revascularization (aHR 1.317; 95% CI 1.031-1.681; p = 0.028), target lesion vascularization, and target vessel vascularization in group B were significantly higher than in group C. CONCLUSIONS: A statin and RASI combination therapy significantly reduced the cumulative incidence of MACEs compared with a monotherapy of these drugs. Moreover, the combination therapy showed a reduced all-cause death rate compared with statin monotherapy, and a decreased repeat revascularization rate compared with RASI monotherapy.

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.

Time-Specific Associations of Tumor Necrosis Factor-α Levels and Polymorphisms (-850 C/T or -308 G/A) With Suicidal Ideation in Acute Coronary Syndrome Patients.

Background: Considering the association of inflammation with suicide and acute coronary syndrome (ACS), we investigated the individual and interactive effects of serum tumor necrosis factor-alpha (sTNFα) levels and two polymorphisms (-850 C/T and -308 G/A) on suicidal ideation (SI) after ACS. Methods: The SI status using items on the Montgomery-Åsberg Depression Rating Scale (MADRS), related covariates including sociodemographic and clinical characteristics, sTNFα levels, and tumor necrosis factor-alpha (TNF-α) polymorphisms were evaluated in 969 patients within 2 weeks after ACS. Of the patients, 711 were evaluated 1 year later for SI. Multivariate logistic regression models were used to calculate individual and interactive associations after adjusting for the covariates. Results: Higher (vs. lower) sTNFα levels and the -850 C/T or T/T (vs. C/C) polymorphism were significantly associated with SI 2 weeks after ACS, while only higher sTNFα levels were significantly associated with SI after 1 year. Significant interactive effects were detected between sTNFα (higher) levels and the -850 C/T (C/C or C/T) polymorphism on SI 2 weeks after ACS and between the two (-850 CC or CT and -308 G/A or AA) polymorphisms on SI 1 year after ACS. Conclusions: The sTNFα level and two polymorphisms (-850C/T and -308 G/A), separately or in combination, could be time-specific biomarkers for SI in ACS. Focused interventions for ACS patients at risk of SI might reduce the suicidal burden in patients with ACS.

Impact of renin angiotensin system inhibitor on 3-year clinical outcomes in acute myocardial infarction patients with preserved left ventricular systolic function: a prospective cohort study from Korea Acute Myocardial Infarction Registry (KAMIR).

BACKGROUND: Patients with acute myocardial infarction (AMI) are usually treated with angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) if ACEIs are not tolerated. However, there is no data regarding the impact of switching from ACEIs to ARBs on long-term clinical outcomes in AMI patients with preserved left ventricular (LV) systolic function especially beyond 1 year. To investigate the effectiveness of treatment with ACEIs or ARBs on clinical outcomes over 3 years in AMI patients with preserved LV systolic function following percutaneous coronary intervention. METHOD: It is a prospective cohort study using data from a nationwide large scale registry with 53 hospitals involved in treatment of acute myocardial infarction (AMI) in Korea. Between March 2011 and September 2015, we enrolled 6236 patients with AMI who underwent primary percutaneous coronary intervention and had a left ventricular ejection fraction ≥ 50%. Main outcome measures composite of total death or recurrent AMI over 3 years after AMI. Patients were divided into an ACEI group (n = 2945), ARB group (n = 2197), or no renin-angiotensin system inhibitor (RASI) treatment (n = 1094). We analyzed patients who changed treatment. Inverse probability of treatment weighting (IPTW) analysis was also performed. RESULTS: After the adjustment with inverse probability weighting, the primary endpoints at 1 year, AMI patients receiving ACEIs showed overall better outcomes than ARBs [ARBs hazard ratio (HR) compared with ACEIs 1.384, 95% confidence interval (CI) 1.15-1.71; P = 0.003]. However, 33% of patients receiving ACEIs switched to ARBs during the first year, while only about 1.5% switched from ARBs to ACEIs. When landmark analysis was performed from 1 year to the end of the study, RASI group showed a 31% adjusted reduction in primary endpoint compared to patients with no RASI group (HR, 0.74; 95% CI 0.56-0.97; P = 0.012). CONCLUSIONS: This result suggests that certain patients got benefit from treatment with ACEIs in the first year if tolerated, but switching to ARBs beyond the first year produced similar outcomes. RASI beyond the first year reduced death or recurrent AMI in AMI patients with preserved LV systolic function. CRIS Registration number: KCT0004990.

Clinical Implication of 'Obesity Paradox' in Elderly Patients With Acute Myocardial Infarction.

BACKGROUND: The clinical impact of body mass index (BMI), especially in the elderly with acute myocardial infarction (AMI), has not been sufficiently evaluated. The purpose of this study was to elucidate the clinical impact of BMI in very old patients (≥80 years) with AMI. METHODS: The study analysed 2,489 AMI patients aged ≥80 years from the Korea Acute Myocardial Infarction Registry and the Korea Working Group on Myocardial Infarction (KAMIR/KorMI) registries between November 2005 and March 2012. The study population was categorised into four groups based on their BMI: underweight (n=301), normal weight (n=1,150), overweight (n=890), and obese (n=148). The primary endpoint was major adverse cardiovascular event (MACE), a composite of cardiac death, myocardial infarction, target lesion revascularisation, and target vessel revascularisation. RESULTS: Baseline characteristics among the four groups were similar, except for hypertension (45.1 vs 58.4 vs 66.2 vs 69.9%, respectively; p<0.001) and diabetes (16.6 vs 23.6 vs 30.7 vs 35.1%, respectively; p<0.001). Coronary care unit length of stay was significantly different among the four groups during hospitalisation (5.3±5.9 vs 4.8±6.8 vs 4.2±4.0 vs 3.5±2.1 days; p=0.007). MACE (16.9 vs 14.9 vs 13.7 vs 8.8%; p=0.115) and cardiac death (10.3 vs 8.4 vs 7.9 vs 4.1%; p=0.043) less frequently occurred in the obese group than in other groups during the 1-year follow-up. A multivariate regression model showed obese status (BMI ≥27.5 kg/m2) as an independent predictor of reduced MACE (hazard ratio [HR], 0.20; 95% confidence interval [CI], 0.06-0.69; p=0.010) along with reduced left ventricular ejection fraction (≤40%) as a predictor of increased MACE (HR,1.87; 95% CI, 1.31-2.68; p=0.001). CONCLUSION: Body mass index in elderly patients with acute myocardial infarction was significantly associated with coronary care unit stay and clinical cardiovascular outcomes.

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.

Sleep problems associated with long-term mortality in acute coronary syndrome: Effects of depression comorbidity and treatment.

OBJECTIVES: The effects of sleep disturbance and its treatment on the prognosis of patients with acute coronary syndrome (ACS) are not well understood. This study investigated the impact of sleep disturbance on long-term all-cause mortality, according to depression comorbidity and treatment, in patients with ACS. METHODS: A cross-sectional baseline study and a nested 24-week double-blind escitalopram-placebo controlled trial were carried out from May 2007 to March 2013; 5-12-year follow-up for all-cause mortality was conducted. A total of 1152 patients with ACS were stratified by baseline depression comorbidity and treatment allocation into four groups: no depression (N = 706), depression on escitalopram (N = 149), depression on placebo (N = 151), and depression on medical care as usual (CAU; N = 146). Sleep disturbance was evaluated by the Leeds Sleep Evaluation Questionnaire. During the 5-12-year follow-up, Kaplan-Meyer event rates for all-cause mortality were calculated; hazard ratios (HRs) using Cox regression models were estimated after adjustment for a range of covariates. RESULTS: Worse sleep states at baseline increased long-term all-cause mortality in all patients (HRs 1.08-1.59). The associations between worse sleep states and long-term all-cause mortality were significant in patients without depression and in patients with depression who received CAU, but not in patients with depression who participated in the 24-week trial. CONCLUSIONS: Routine evaluations of sleep disturbance in ACS and further treatment allocation may contribute to reducing long-term mortality associated with the disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier for the 24 week drug trial, NCT00419471.

Ten-Year Outcomes After Drug-Eluting Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Disease: Extended Follow-Up of the PRECOMBAT Trial.

BACKGROUND: Long-term comparative outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents and coronary-artery bypass grafting (CABG) for left main coronary artery disease are highly debated. METHODS: In the PRECOMBAT trial (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease), patients with unprotected left main coronary artery disease were randomly assigned to undergo PCI with sirolimus-eluting stents (n=300) or CABG (n=300) in 13 hospitals in Korea from April 2004 to August 2009. The follow-up was extended to at least 10 years for all patients (median, 11.3 years). The primary outcome was the incidence of major adverse cardiac or cerebrovascular events (composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization). RESULTS: At 10 years, a primary outcome event occurred in 29.8% of the PCI group and in 24.7% of the CABG group (hazard ratio [HR] with PCI vs CABG, 1.25 [95% CI, 0.93-1.69]). The 10-year incidence of the composite of death, myocardial infarction, or stroke (18.2% vs 17.5%; HR 1.00 [95% CI, 0.70-1.44]) and all-cause mortality (14.5% vs 13.8%; HR 1.13 [95% CI, 0.75-1.70]) were not significantly different between the PCI and CABG groups. Ischemia-driven target-vessel revascularization was more frequent after PCI than after CABG (16.1% vs 8.0%; HR 1.98 [95% CI, 1.21-3.21). CONCLUSIONS: Ten-year follow-up of the PRECOMBAT trial of patients with left main coronary artery disease randomized to PCI or CABG did not demonstrate significant difference in the incidence of major adverse cardiac or cerebrovascular events. Because the study was underpowered, the results should be considered hypothesis-generating, highlighting the need for further research. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03871127 and NCT00422968.

Metabolic alterations in acute myocardial ischemia-reperfusion injury and necrosis using in vivo hyperpolarized [1-13C] pyruvate MR spectroscopy.

This study aimed to investigate real-time early detection of metabolic alteration in a rat model with acute myocardial ischemia-reperfusion (AMI/R) injury and myocardial necrosis, as well as its correlation with intracellular pH level using in vivo hyperpolarized [1-13C] pyruvate magnetic resonance spectroscopy (MRS). Hyperpolarized 13C MRS was performed on the myocardium of 8 sham-operated control rats and 8 rats with AMI/R injury, and 8 sham-operated control rats and 8 rats with AMI-induced necrosis. Also, the correlations of levels of [1-13C] metabolites with pH were analyzed by Spearman's correlation test. The AMI/R and necrosis groups showed significantly higher ratios of [1-13C] lactate (Lac)/bicarbonate (Bicar) and [1-13C] Lac/total carbon (tC), and lower ratios of 13C Bicar/Lac + alanine (Ala), and 13C Bicar/tC than those of the sham-operated control group. Moreover, the necrosis group showed significantly higher ratios of [1-13C] Lac/Bicar and [1-13C] Lac/tC, and lower ratios of 13C Bicar/Lac + Ala and 13C Bicar/tC than those of the AMI/R group. These results were consistent with the pattern for in vivo the area under the curve (AUC) ratios. In addition, levels of [1-13C] Lac/Bicar and [1-13C] Lac/tC were negatively correlated with pH levels, whereas 13C Bicar/Lac + Ala and 13C Bicar/tC levels were positively correlated with pH levels. The levels of [1-13C] Lac and 13C Bicar will be helpful for non-invasively evaluating the early stage of AMI/R and necrosis in conjunction with reperfusion injury of the heart. These findings have potential application to real-time evaluation of cardiac malfunction accompanied by changes in intracellular pH level and enzymatic activity.

Association between Obsessive-Compulsive Symptoms and Long-Term Cardiac Outcomes in Patients with Acute Coronary Syndrome: Effects of Depression Comorbidity and Treatment.

OBJECTIVE: The role of obsessive-compulsive symptoms (OCS) in patients with acute coronary syndrome (ACS) is not well elucidated. This study investigated the association between OCS and the long-term prognosis of ACS in tandem with depression comorbidity and treatment. METHODS: A cross-sectional baseline study and a nested 24-week double-blind escitalopram-placebo controlled trial were carried out between May 2007 and March 2013, and then a 5-12-year follow-up for major adverse cardiac events (MACE) was conducted. A total of 1,152 patients with ACS were stratified by baseline depression comorbidity and treatment allocation into four groups: no depression (706 patients), depression and taking escitalopram (149 patients), depression and taking a placebo (151 patients), and depression and receiving medical care as usual (CAU; 146 patients). OCS were evaluated using the Symptom Checklist-90-Revised Obsessive-Compulsive symptom domain. During the follow-up, Kaplan-Meier event rates for MACE outcomes were calculated, and hazard ratios were estimated using Cox regression models after adjusting for a range of covariates. RESULTS: A higher OCS score at baseline was associated with a worse ACS prognosis after adjusting for relevant covariates and across MACE outcomes. This association varied according to the depression comorbidity. The association was significant in patients without depression and depressive patients receiving placebos and CAU, but not in depressive patients on escitalopram. CONCLUSION: Evaluating OCS and depression is recommended during the early phase of ACS. Treatment for OCS may improve the longterm cardiac outcomes of patients with ACS.

Long-Term Comparison of Platinum Chromium Everolimus-Eluting Stent vs. Cobalt Chromium Zotarolimus-Eluting Stent　- 3-Year Outcomes From the HOST-ASSURE Randomized Clinical Trial.

BACKGROUND: There are limited data on the long-term outcome of platinum chromium-based everolimus-eluting stents (PtCr-EES) vs. cobalt chromium-based zotarolimus-eluting stents (CoCr-ZES).Methods and Results:A total of 3,755 patients undergoing percutaneous coronary intervention (PCI) were randomized 2:1 to PtCr-EES or CoCr-ZES, and 96.0% of patients completed the 3-year clinical follow-up. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and clinically-driven target lesion revascularization (TLR). At 3 years, TLF occurred in 5.3% and in 5.4% of the PtCr-EES and CoCr-ZES groups, respectively (hazard ratio 0.978; 95% confidence interval 0.730-1.310, P=0.919). There were no significant differences in the individual components of TLF. Routine angiographic follow-up was performed in 38.9% of the total patients. In a landmark analysis of the subgroup that had follow-up angiography, the clinically-driven TLR rate of CoCr-ZES was significantly higher than PtCr-EES group during the angiography follow-up period (P=0.009). Overall definite and probable stent thrombosis rates were very low in both groups (0.5% vs. 0.6%, P=0.677). CONCLUSIONS: PtCr-EES and CoCr-ZES had similar and excellent long-term outcomes in both efficacy and safety after PCI in an all-comer population.

Efficacy of dextran and peptide-everolimus bi-directional stent.

Everolimus inhibits stent restenosis and the WKYMV (fluorescein isothiocyanate) peptide promotes endothelial homing. Dextran is a natural polymer that is widely used as a pharmaceutical agent. The purpose of this study was to develop a double-drug-coated stent using a bidirectional coating system and to examine the surface shape with in vitro experiments. Stent length was 16 mm and strut thickness was 70 µm (Chonnam National University Hospital Tiger stent). Optical and scanning electron microscopy showed good coating without cracks or bubbles. Fluorescein isothiocyanate-peptide was dip-coated on the lumen and the abluminal surface was coated with everolimus and dextran. Stents were coated with dextran, everolimus, or everolimus-dextran. The radial force and flexibility were measured to determine the mechanical properties. Contact angle testing was performed in all groups. Dextran and peptide as hydrophilic substances and everolimus as a hydrophobic substance were each coated on cover glasses (cobalt-chromium). A10 and human umbilical vein endothelial cells were used in the experiments. Water and dimethyl sulfoxide served as a control, and three drug groups were tested: peptide-everolimus, everolimus-dextran, and peptide-everolimus-dextran. Immunocytochemistry was performed to assess cell adhesion. Light intensity was plotted according to the average on nuclear staining. Experiments were conducted using 5-bromo-2'-deoxyuridine to investigate A10 and human umbilical vein endothelial cell proliferation. Cell adhesion and proliferation of peptide-everolimus-dextran were inhibited at A10, and human umbilical vein endothelial cell was found to proliferate with cell adhesion. On conclusion, dextran and peptide-everolimus bidirectional stent is effective in re-endothelialization and inhibition of cell proliferation.

Estrategia de tratamiento de lesiones en bifurcación tratadas con ICP primaria en el contexto del IAMCEST. Registro COBIS II / Treatment strategy for STEMI with bifurcation culprit lesion undergoing primary PCI: the COBIS II Registry

Introducción y objetivos: Hay poca información acerca de la estrategia de tratamiento de lesiones en bifurcación en el contexto del infarto agudo de miocardio con elevación del segmento ST (IAMCEST). Este estudio comparó los resultados clínicos entre 2 estrategias de tratamiento, 1 y 2 stents, en estos pacientes con lesiones en bifurcación tratados con intervención coronaria percutánea (ICP) primaria en el contexto del IAMCEST. Métodos: El COronary BIfurcation Stenting II es un registro retrospectivo multicéntrico que incluyó a 2.897 pacientes consecutivos con lesiones en bifurcación tratados con ICP y stents farmacoactivos desde enero de 2003 a diciembre de 2009. En el registro había 367 pacientes (12,7%) con IAMCEST, de los que se trató a 304 con estrategia de 1 stent y a 63 con la estrategia de 2 stents; el 77,1% de los pacientes tratados con ICP primaria recibieron stents farmacoactivos de primera generación. Para el ajuste de factores de confusión, se usó el método de ponderación por el inverso de la probabilidad de tratamiento. El objetivo primario fue el compuesto de eventos adversos cardiovasculares mayores (MACE): muerte cardiaca, infarto agudo de miocardio, revascularización de la lesión diana y trombosis del stent. Resultados: La media de seguimiento fue de 38 meses. El diámetro de la estenosis de la rama secundaria tras el procedimiento fue significativamente diferente entre los grupos de 1 y 2 stents (el 42,7 frente al 9,7%; p < 0,001). Después de llevar a cabo la ponderación por el inverso de la probabilidad de tratamiento, la tasa de MACE fue significativamente mayor en el grupo de 2 stents que en el de 1 (HR = 1,85; IC95%, 1,19-2,87; p = 0,006), principalmente por las mayores tasas de revascularización de la lesión diana y trombosis del stent. Conclusiones: En pacientes con IAMCEST y lesiones culpables en bifurcación tratados con ICP primaria, la estrategia de 2 stents tuvo una tasa de MACE significativamente mayor que la de 1 stent, a pesar del éxito del tratamiento inicial de la rama secundaria. Sin embargo, este resultado debería interpretarse con cautela, dado que este estudio no refleja la práctica clínica actual

Introduction and objectives: There are limited data on the preferred treatment strategy in ST-segment elevation myocardial infarction (STEMI) patients with bifurcation lesions. This study aimed to compare clinical outcomes between 1-stent and 2-stent strategies in STEMI patients with bifurcation lesions undergoing primary percutaneous coronary intervention (PCI). Methods: The COronary BIfurcation Stenting II is a retrospective multicenter registry of 2897 consecutive patients with bifurcation lesions undergoing PCI with drug-eluting stents from January 2003 through December 2009. Among the registered population, 367 (12.7%) patients had STEMI; of these, a 1-stent strategy was used in 304 patients and a 2-stent strategy in 63 patients; 77.1% of the patients received primary PCI with a first-generation drug-eluting stent. The inverse-probability-of-treatment-weighting method was used to adjust for confounding factors. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiac death, myocardial infarction, target lesion revascularization, and stent thrombosis. Results: The median length of follow-up was 38 months. Postprocedural side branch diameter stenosis differed significantly between the 2 groups (1-stent vs 2-stent, 42.7% vs 9.7%; P < .001). After the performance of inverse-probability-of-treatment-weighting methods, the rate of MACE was significantly higher in the 2-stent group than in the 1-stent group (HR, 1.85; 95%CI, 1.19-2.87; P = .006), mainly driven by target lesion revascularization and stent thrombosis. Conclusions: In STEMI patients with bifurcation culprit lesions undergoing primary PCI, the 2-stent strategy had significantly higher rates of MACE than the 1-stent strategy, despite successful treatment of the side branch. However, this result should be interpreted with caution because this study does not reflect current practice

10-Year Outcomes of Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Artery Disease.

BACKGROUND: Comparative outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for left main coronary artery (LMCA) disease were previously reported. However, data on very long-term (>10 years) outcomes are limited. OBJECTIVES: The authors compare 10-year outcomes after PCI and CABG for LMCA disease. METHODS: In this observational study of the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty versus Surgical Revascularization) registry, the authors evaluated 2,240 patients with unprotected LMCA disease who underwent PCI (n = 1,102) or underwent CABG (n = 1,138) between January 2000 and June 2006. Adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction, or stroke; and target-vessel revascularization) were compared with the use of propensity scores and inverse-probability-weighting adjustment. The follow-up was extended to at least 10 years of all patients (median 12.0 years). RESULTS: In the overall cohort, there was no significant difference in adjusted risks of death and the composite outcome between the groups up to 10 years. The risk of target-vessel revascularization was significantly higher in the PCI group. In the cohort comparing drug-eluting stents and concurrent CABG, the 2 study groups did not differ significantly in the risks of death and the composite outcome at 5 years. However, after 5 years, drug-eluting stents were associated with higher risks of death (hazard ratio: 1.35; 95% confidence interval: 1.00 to 1.81) and the composite outcome (hazard ratio: 1.46; 95% confidence interval: 1.10 to 1.94) compared with CABG. CONCLUSIONS: In patients with significant LMCA disease, as compared with CABG, PCI showed similar rates of death and serious composite outcomes, but a higher rate of target-vessel revascularization at 10 years. However, CABG showed lower mortality and serious composite outcome rates compared with PCI with drug-eluting stents after 5 years. (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty versus Surgical Revascularization [MAIN-COMPARE]; NCT02791412).

Effect of Side Branch Predilation in Coronary Bifurcation Stenting With the Provisional Approach　- Results From the COBIS (Coronary Bifurcation Stenting) II Registry.

BACKGROUND: Whether side branch (SB) predilation before main vessel (MV) stenting is beneficial is uncertain, so we investigated the effects of SB predilation on procedural and long-term outcomes in coronary bifurcation lesions treated using the provisional approach.Methods and Results:A total of 1,083 patients with true bifurcation lesions undergoing percutaneous coronary intervention were evaluated. The primary outcome was a major adverse cardiovascular event (MACE): cardiac death, myocardial infarction, or target lesion revascularization. SB predilation was performed in 437 (40.4%) patients. Abrupt (10.5% vs. 11.3%; P=0.76) or final SB occlusion (2.7% vs. 3.9%; P=0.41) showed no differences between the predilation and non-predilation groups. The rates of angiographic success (69.1% vs. 52.9%, P<0.001) and SB stent implantation (69.1% vs. 52.9%, P<0.001) were significantly higher in the predilation group. During a median follow-up of 36 months, we found no significant difference between the groups in the rate of MACE (9.4% vs. 11.5%; P=0.67) in a propensity score-matched population. In subgroup analysis, patients with minimal luminal diameter of the parent vessel ≤1 mm benefited from SB predilation in terms of preventing abrupt SB occlusion (P for interaction=0.04). CONCLUSIONS: For the treatment of true bifurcation lesions, SB predilation improved acute angiographic and procedural outcomes, but could not improve long-term clinical outcomes. It may benefit patients with severe stenosis in the parent vessel.