The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis-a nationwide cohort study.

BACKGROUND: In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies. METHODS: This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone. RESULTS: The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052-1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454-0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529-0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478-0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231-1.880), ICH (aHR 2.045, 95% CI 1.329-3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB. CONCLUSIONS: For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.

Which dose of apixaban is suitable for Asian patients with atrial fibrillation who have a serum creatinine < 1.5 mg/dL but an estimated glomerular filtration rate < 50 mL/min?

Introduction: Reduced-dose (Low-dose [LD]) apixaban is recommended in patients with atrial fibrillation (AF) who fulfill 2 of 3 criteria: age ≥ 80 years, body weight ≤ 60 kg, and a serum creatinine (sCr) ≥ 1.5 mg/dl. However, the suitable (appropriate) dose for Asian patients who have a sCr < 1.5 mg/dl but an estimated glomerular filtration rate (eGFR) < 50 mL/min is unknown. Methods: This is a retrospective study using the Chang Gung Memorial hospital medical database in Taiwan. A total of 13,508 AF patients receiving oral anticoagulants (OACs) from 2012 to 2018 were reviewed and 1595 patients with a sCr < 1.5 mg/dL and an eGFR < 50 mL/min who met 1 criterion of dose reduction of apixaban other than sCr (that is, age ≥ 80 years or body weight < 60 kg) were identified. Clinical outcomes were compared between LD and SD apixaban versus warfarin. Results: Their OACs use was as follows: 343 receiving apixaban (128 patients on standard dose [SD] and 215 on LD), 174 receiving warfarin, and 1078 on other NOACs. Patients with an eGFR < 50 mL/min had higher risk of mortality (adjusted hazard ratio [aHR], 1.264; 95 % confidence interval [CI], 1.086-1.472) and composite endpoint of 'ischemic stroke/systemic embolism (IS/SE) or major bleeding or mortality (aHR, 1.202; 95 % CI, 1.056-1.370) compared to those with an eGFR ≥ 50 mL/min whereas the risk of IS/SE and major bleeding were similar. LD apixaban was associated with lower risk of composite endpoint of IS/SE or major bleeding (aHR, 0.567; 95 % CI, 0.331 - 0.972), mortality (aHR, 0.336; 95 % CI, 0.138 - 0.815), and 'IS/SE or major bleeding or mortality (aHR, 0.551; 95 % CI, 0343 - 0.886) compared to warfarin while the risk was comparable between SD apixaban and warfarin (aHR, 0.745; 95 % CI, 0.402 - 1.378; aHR, 0.407; 95 % CI, 0.145 - 1.143; aHR, 0.619; 95 % CI, 0.354 - 1.084, respectively). Conclusion: In patients with sCr < 1.5 mg/dL and eGFR < 50 mL/min, SD and LD apixaban were comparable in the prevention of IS/SE, but LD apixaban was superior in reducing the composite endpoint of 'IS/SE or major bleeding or mortality'. Therefore, LD apixaban might be a preferred dose for this population.

Risk of Incident Atrial Fibrillation and Subsequent Use of Oral Anticoagulants in Patients with Dementia.

BACKGROUND: Dementia and atrial fibrillation (AF) have many shared risk factors. Besides, patients with dementia are under-represented in randomized trials, and even if AF is present, oral anticoagulants (OACs) are not prescribed frequently. This study aimed to report the incidence of newly diagnosed AF in dementia patients, and the impacts of use of vitamin K antagonist (VKA; e.g., warfarin) and non-VKA OAC (NOACs) on stroke and bleeding outcomes. METHODS: Our study utilized the Taiwan National Health Insurance Research Database. A total of 554,074 patients with dementia were compared with 554,074 age- and sex-matched patients without dementia regarding the risk of incident AF. Among patients with dementia who experienced incident AF, the risks of clinical events of patients treated with warfarin or NOACs were compared with those without OACs (reference group). RESULTS: The risk of incident AF was greater for patients with dementia compared with those without (adjusted hazard ratio [aHR]: 1.054; 95% confidence interval [CI]: 1.040-1.068 for all types of dementia, aHR: 1.035; 95% CI: 1.020-1.051 for presenile/senile dementia, and aHR: 1.125; 95% CI: 1.091-1.159 for vascular dementia). Among patients with dementia and experienced incident AF, warfarin use was associated with a higher risk of ischemic stroke (aHR: 1.290; 95% CI: 1.156-1.440), intracranial hemorrhage (ICH; aHR: 1.678; 95% CI: 1.346-2.090), and major bleeding (aHR: 1.192; 95% CI: 1.073-1.323) compared with non-OACs. NOAC use was associated with a lower risk of ischemic stroke (aHR: 0.421; 95% CI: 0.352-0.503) and composite risk of ischemic stroke or major bleeding (aHR: 0.544; 95% CI: 0.487-0.608) compared with non-OACs. These results were consistent among the patients after the propensity matching. CONCLUSION: In this large nationwide cohort, the risk of newly diagnosed AF was higher in patients with dementia (all dementia, presenile/senile dementia, and vascular dementia) compared with those without dementia. For patients with dementia who experienced incident AF, NOAC use was associated with a better clinical outcome compared with non-OAC. Patients with dementia require a holistic approach to their care and management, including the use of NOACs to reduce the risks of clinical events.

Sex difference in the association of the triglyceride glucose index with obstructive coronary artery disease.

Insulin resistance (IR) is associated with cardiovascular disease in non-diabetic patients. The triglyceride-glucose (TyG) index, incorporating serum glucose and insulin concentrations, is a surrogate insulin resistance marker. We investigated its association with obstructive coronary artery disease (CAD) and sex differences therein. Patients with stable angina pectoris requiring invasive coronary angiography between January 2010 and December 2018 were enrolled. They were divided into two groups according to TyG index. Two interventional cardiologists diagnosed obstructive CAD by angiography review. Demographic characteristics and clinical outcomes were compared between groups. Relative to lower index, patients with higher (≥ 8.60) TyG index had higher BMIs and more prevalent hypertension, diabetes, and elevated lipid profiles [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), fasting plasma glucose (FPG)]. Higher TyG index increased women's obstructive CAD risk after multivariate adjustment (adjusted odds ratio (aOR) 2.15, 95% confidence interval (95% CI) 1.08-4.26, p = 0.02) in non-diabetic populations compared with men. No sex difference was found for diabetic patients. Higher TyG index significantly increased the obstructive CAD risk, overall and for non-diabetic women. Larger-scale studies are needed to confirm our findings.

Plasma asymmetric dimethylarginine is associated with vulnerable plaque and long-term outcomes in stable coronary artery disease.

Asymmetric dimethylarginine (ADMA) is considered to be an atherogenic molecule. We aimed to investigate the relationship between ADMA and plaque vulnerability assessed by optical coherence tomography (OCT) in patients with stable coronary artery disease (CAD). Two hundred and forty-five patients with stable CAD undergoing OCT-guided percutaneous coronary intervention were included in this study and were divided into two groups according to their ADMA levels. Micro-vessel, macrophage accumulation, thin-cap fibroatheroma, intra-plaque calcium and lipid core content, and vulnerable score (VS) were evaluated by OCT analysis. The patients with higher ADMA levels had significantly higher calcium and lipid content (p < 0.001, respectively). There were significantly more micro-vessel and macrophage (32.8%, p = 0.004 and 52.5%, p < 0.001, respectively) and higher VS (87.7 ± 17.6, p < 0.001) in the higher ADMA group. Moreover, plasma ADMA level was significantly correlated with the intra-plaque lipid, calcium content and VS (p < 0.001, respectively). Plasma ADMA level was identified as an independent predictor of future adverse cardiovascular events, following OCT-guided PCI. In patients with stable CAD, higher plasma ADMA levels were significantly associated with the presence of intra-plaque lipid, calcification, vulnerable plaque, and poor long-term outcomes.

The clinical impact of serum 1,5-anhydro-D-glucitol levels on coronary artery calcification and adverse outcomes assessed by coronary optical coherence tomography in diabetic patients.

Background: Serum 1,5-anhydro-D-glucitol (1,5-AG) is a novel biomarker for short-term glycemic status and postprandial hyperglycemia. The association between serum 1,5-AG levels and coronary artery calcification (CAC) through a quantitative assessment using optical coherence tomography (OCT) is unclear. We aimed to evaluate this association using OCT in patients with diabetes mellitus (DM). Methods: From June 2016 to December 2019, we prospectively enrolled 256 patients who underwent OCT-guided percutaneous coronary intervention (PCI). Half of the patients had diabetes. Patients were followed up for a mean period of 1.8 ± 0.8 years (median: 2.2 years). The relative calcium index and relative lipid core index measured by quantitative OCT analysis were used to evaluate the intra-plaque calcium and lipid levels of culprit plaques. We also analyzed the correlation between serum 1,5-AG levels and long-term major adverse cardiovascular events. Results: Serum 1,5-AG levels were significantly lower in diabetic patients than in non-diabetic patients (DM vs. non-DM: 55.6 ± 27.9 µg/mL vs. 63.7 ± 26.1 µg/mL, p = 0.016), and lower in fibrocalcified lesions than in fibrotic or fibrolipidic lesions (fibrocalcified vs. fibrotic or fibrolipidic: 42.8 ± 19.1 vs. 72.9 ± 25.2 or 66.4 ± 27.5 µg/mL, p < 0.001, respectively). In addition, we found a significant inverse correlation between serum 1,5-AG levels and relative calcium index (r = -0.729, p < 0.001). In multivariate Cox regression analysis, low serum 1,5-AG level was identified as an independent predictor for major adverse cardiovascular events in diabetic patients (p = 0.043), but not in non-diabetic patients (p = 0.748) after adjusting for age and sex. Conclusion: This study revealed that low serum 1,5-AG levels were associated with an increased risk of CAC as assessed by OCT, especially in diabetic patients. Low serum 1,5-AG levels may predict future major adverse cardiovascular events in diabetic patients undergoing OCT-guided PCI.

Effect of timing of coronary revascularization in patients with post-infectious myocardial infarction.

OBJECTIVES: Acute infection is a well-known provocative factor of acute myocardial infarction (AMI). Prognosis is worse when it is associated with sepsis. Coronary revascularization is reported to provide benefit in these patients; however, the optimal timing remains uncertain. METHODS: This retrospective study was performed at a tertiary center in Taipei from January 2010 to December 2017. 1931 patients received coronary revascularization indicated for AMI. Among these, 239 patients were hospitalized for acute infection but later developed AMI. Patients with either an ST-elevation myocardial infarct or the absence of obstructive coronary artery disease were excluded. Revascularization was performed via either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). We defined early and delayed revascularization groups if it was performed within or after 24 hours of the diagnosis of AMI, respectively. We evaluated whether the timing of revascularization altered 30-day and one-year all-cause mortality. RESULTS: At one month, 24 (26%) patients died in early revascularization group and 32 (22%) patients in delayed revascularization group. At one year, 40 (43%) and 59 (40%) patients died on early and delayed revascularization groups respectively. Early revascularization did not result in lower 30-day all-cause mortality (P = 0.424), and one-year all-cause mortality (Hazard ratio (HR): 0.935; 95% confidence interval (CI): 0.626-1.397, P = 0.742) than delay revascularization. CONCLUSIONS: Timing of coronary revascularization of post infectious acute coronary syndrome may be arranged according to individual risk category as those without sepsis.

Risk of Ischemic Bowel Disease in Patients With Atrial Fibrillation Receiving Warfarin or Non-vitamin K Antagonist Oral Anticoagulants.

Background: Although atrial fibrillation (AF) is a risk factor for ischemic bowel disease, data regarding the incidence of ischemic bowel disease in patients with anticoagulated AF were limited. Methods: The present study used the Taiwan NHIRD and included newly diagnosed patients with AF aged ≥ 20 years without ischemic bowel disease from 2012 to 2018. A total of 69,549 patients taking warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) constituted the final study group. We aimed to study the incidence of ischemic bowel disease in patients with AF receiving warfarin or NOACs. Secondary endpoints were also analyzed, including ischemic stroke, systemic embolism, myocardial infarction, mortality, intracranial hemorrhage (ICH), major bleeding, and composite adverse events (ischemic bowel disease or ICH or major bleeding). Results: There were 43,787 patients taking NOACs and 25,762 patients taking warfarin. The overall incidence rate of ischemic bowel disease was 0.036% per year and increased with the CHA2DS2-VASc scores [0.013% for patients with a CHA2DS2-VASc score of 0 (men) or 1 (women), 0.022% for those with a CHA2DS2-VASc score of 1 (men) or 2 (women), and 0.039% for those with a CHA2DS2-VASc score ≥ 2 (men) or ≥ 3 (women)]. The risk of ischemic bowel disease was similar between NOAC and warfarin groups (0.036%/year vs. 0.037%/year; adjusted hazard ratio 0.802, p = 0.430), whereas the NOAC group had a significantly lower risk of secondary endpoints compared to the warfarin group. Conclusion: We reported the incidence of ischemic bowel disease in patients with anticoagulated AF from a nationwide cohort database and observed a positive correlation between the increase of CHA2DS2-VASc scores and the incidence rate. Moreover, NOAC was as effective as warfarin for the risk of ischemic bowel disease.

Effects of aggressive predilatation, sizing, and postdilatation strategy for coronary bioresorbable vascular scaffolds implantation.

BACKGROUND: The results of the recent Amsterdam Investigator-Initiated Absorb Strategy All-Comers trial showed that the predilatation, sizing, and postdilatation (PSP) technique did not lower the long-term rates of scaffold thrombosis and adverse events. We evaluated the impact of aggressive PSP bioresorbable vascular scaffold (BRS) implantation on the short- and long-term clinical outcomes. METHODS: From June 2014 to December 2016, 150 patients with BRS implantation were enrolled and received successful percutaneous coronary intervention (PCI), of whom 104 received aggressive PSP technique (high-pressure predilatation and lesion preparation in addition to the traditional PSP technique). Short- and long-term outcomes were compared. RESULTS: All patients underwent successful PCI and BRS implantation with final Thrombolysis in Myocardial Infarction grade 3 flow. The baseline and procedure characteristics were similar in both groups. Debulking techniques were used in 13 (8.7%) patients. Intracoronary imaging modalities were used in 73 (48.7%) patients. After BRS implantation, no adverse events were observed within 30 days in both groups. During the mean follow-up period of 2.98 ± 0.77 years, 12 (8.0%) patients experienced major adverse cardiovascular events (MACEs), including one cardiovascular death (0.6%), three nonfatal myocardial infarction (2.0 %), and 11 target-vessel revascularization (7.3 %). Multivariate Cox regression analysis showed that aggressive PSP remained an independent protective factor for MACEs. Moreover, the use of intracoronary imaging and rotablation atherectomy was associated with better clinical outcomes. CONCLUSION: Lesion preparation by aggressive PSP in BRS implantation was associated with better long-term clinical outcomes.

Optimal anticoagulation in elderly patients with atrial fibrillation: Which drug at which dose?

Aging is an important risk factor for adverse events in elderly patients with atrial fibrillation (AF) and complicates the management of anticoagulation. Underuse of oral anticoagulants (OACs) is common in elderly patients because of comorbidities, the altered physiological function of multiple organs, frailty, risk of falls, and the lack of randomized controlled trials (RCTs) specifically for elderly patients. Nevertheless, current data still support OACs use for reducing ischemic stroke with positive net clinical benefits. Sub-analyses of RCTs and real-world cohort studies showed that non-vitamin K antagonist OACs (NOACs) would be more favorable choices compared to warfarin for stroke prevention in the elderly. This review will discuss important data on stroke prevention and the use of NOACs in elderly AF patients.

Technical Characteristics and Feasibility of Coronary Angiography and Percutaneous Coronary Interventions Performed after Transcatheter Aortic Valve Replacement with Self-Expanding Valves.

BACKGROUND: Coronary angiography (CA) or percutaneous coronary intervention (PCI) after transcatheter aortic valve replacement (TAVR) may become technically challenging after implantation of the self-expanding Medtronic CoreValve (MCV) device, which extends above the coronary ostia. The aim of this study was to investigate the incidence and feasibility of CA or PCI and the outcomes of PCI after TAVR with the MCV device. METHODS: From July 2014 to April 2020, among 209 patients treated with TAVR with a MCV device, 14 (7%) underwent CA or PCI after the procedure at a mean duration of 28 ± 15 months at our institution. RESULTS: The mean age of the patients was 83 ± 6 years. Thirteen (93%) patients underwent CA due to angina symptoms with a positive noninvasive test, and 1 underwent CA for acute coronary syndrome. Most of the CA and PCI procedures were performed through a radial approach: 11 patients (79%) via the right radial artery, 1 (7%) the left radial artery, and 2 (14%) through the right femoral artery. CA of the left and right coronary arteries was successfully achieved in 13 patients (93%) with Judkin left (3.5 to 5) diagnostic catheters and in 11 patients (79%) with Judkin right (4) diagnostic catheters. The second-line catheter of choice was the Amplatz left (AL) 1 catheter for the right coronary artery and AL 2 for the left coronary artery. Procedural success was achieved in all 5 patients who underwent post-TAVR PCI without procedural or in-hospital complications. The use of a Guideliner microcatheter facilitated stent delivery in one patient. CONCLUSIONS: Coronary angiography or PCI following TAVR with a MCV device is feasible and safe, but requires understanding of the three-dimensional geometry of the prosthetic valve and its relationship to the coronary ostia.

Obesity paradox in patients with chronic total occlusion of coronary artery.

BACKGROUND: Obesity is associated with metabolic syndrome which increases further risk of coronary artery disease and adverse cardiovascular events. Impact of body mass index (BMI) on long-term outcome in patients with coronary chronic total occlusion (CTO) is less clear. METHOD AND RESULTS: From January 2005 to November 2020, a total of 1301 patients with coronary angiographic confirmed CTO were enrolled in our study. Patients were divided into two groups: low BMI group: 18-24.99 kg/m2 and high BMI group ≥25 kg/m2 . Clinical outcomes were 3-year all-cause mortality, 3-year cardiovascular mortality and 3-year non-fatal myocardial infarct. During the 3-year follow-up period, all-cause mortality was significantly higher in patients with low BMI group compared to those in high BMI groups (14% vs. 6%, p = .0001). Kaplan-Meier analysis showed patients with high BMI groups had significant better survival compared with those in low BMI group (p = .0001). In multivariate analysis, higher BMI was independently associated with decreased risk of 3-year all-cause mortality (Hazard ratio [HR]: 0.534; 95% confidence interval [CI]: 0.349-0.819, p = .004) after controlling for age, renal function, prior history of stroke, coronary artery bypass graft, co-morbidities with peripheral arterial disease, heart failure and revascularization status for CTO. In propensity-matched multivariate analysis, high BMI remained a significant predictor of 3-year all-cause mortality (HR, 0.525; 95% CI, 0.346-0.795, p = .002). CONCLUSION: Higher BMI was associated with better long-term outcome in patients with coronary CTO.

Elevated serum galectin-1 concentrations are associated with increased risks of mortality and acute kidney injury in critically ill patients.

BACKGROUND: Galectin-1 (Gal-1), a member of the ß-galactoside binding protein family, is associated with inflammation and chronic kidney disease. However, the effect of Gal-1 on mortality and acute kidney injury (AKI) in critically-ill patients remain unclear. METHODS: From May 2018 to March 2020, 350 patients admitted to the medical intensive care unit (ICU) of Taipei Veterans General Hospital, a tertiary medical center, were enrolled in this study. Forty-one patients receiving long-term renal replacement therapy were excluded. Serum Gal-1 levels were determined within 24 h of ICU admission. The patients were divided into tertiles according to their serum Gal-1 levels (low, serum Gal-1 < 39 ng/ml; median, 39-70 ng/ml; high, ≥71 ng/ml). All patients were followed for 90 days or until death. RESULTS: Mortality in the ICU and at 90 days was greater among patients with elevated serum Gal-1 levels. In analyses adjusted for the body mass index, malignancy, sepsis, Sequential Organ Failure Assessment (SOFA) score, and serum lactate level, the serum Gal-1 level remained an independent predictor of 90-day mortality [median vs. low: adjusted hazard ratio (aHR) 2.11, 95% confidence interval (CI) 1.24-3.60, p = 0.006; high vs. low: aHR 3.21, 95% CI 1.90-5.42, p < 0.001]. Higher serum Gal-1 levels were also associated with a higher incidence of AKI within 48 h after ICU admission, independent of the SOFA score and renal function (median vs. low: aHR 2.77, 95% CI 1.21-6.34, p = 0.016; high vs. low: aHR 2.88, 95% CI 1.20-6.88, p = 0.017). The results were consistent among different subgroups with high and low Gal-1 levels. CONCLUSION: Serum Gal-1 elevation at the time of ICU admission were associated with an increased risk of mortality at 90 days, and an increased incidence of AKI within 48 h after ICU admission.

Non-vitamin K antagonist oral anticoagulants versus warfarin in AF patients ≥ 85 years.

BACKGROUND: Atrial fibrillation (AF) prevalence and its risk of stroke rise with ageing. We aimed to investigate the outcomes of NOAC and warfarin in AF patients aged ≥ 85 years. METHODS: This is a retrospective study using Taiwan National Health Insurance Research Database. A total of 15,361 patients aged ≥ 85 years with AF on oral anticoagulants were identified. The end points included ischaemic stroke, intracranial haemorrhage (ICH), major bleeding, all-cause mortality and composite adverse events (ICH or major bleeding or all-cause mortality). Clinical outcomes were compared between each NOAC and warfarin after propensity matching. RESULTS: Before propensity matching, patients taking warfarin were older, more female with more comorbidities than NOACs users. After propensity matching, baseline characteristics did not differ significantly between matched subjects receiving warfarin and each NOAC. Compared to warfarin, dabigatran was associated with a lower risk of ICH (hazard ratio [HR] 0.496), mortality (HR 0.558) and adverse events (HR 0.628), while rivaroxaban was associated with a lower risk of ischaemic stroke (HR 0.781), ICH (HR 0.453), mortality (HR 0.558) and adverse events (HR 0.636). Apixaban was associated with a lower risk of mortality (HR 0.488) and adverse events (HR 0.557) compared to warfarin. (all P < .05). CONCLUSION: For the efficacy, NOACs were associated with a comparable or lower risk of ischaemic stroke compared to warfarin. For adverse events, NOACs were associated with a lower risk of all-cause mortality and composite adverse events. In the elderly AF population, NOACs could be a more favourable choice for stroke prevention.

Long term clinical impact of successful recanalization of chronic total occlusion in patients with and without type 2 diabetes mellitus.

BACKGROUND: Diabetes mellitus is one of the risk factors for coronary artery disease and frequently associated with multivessels disease and poor clinical outcomes. Long term outcome of successful revascularization of chronic total occlusions (CTO) in diabetes patients remains controversial. METHODS AND RESULTS: From January 2005 to December 2015, 739 patients who underwent revascularization for CTO in Taipei Veterans General Hospital were included in this study, of which 313 (42%) patients were diabetes patients. Overall successful rate of revascularization was 619 (84%) patients whereas that in diabetics and non-diabetics were 265 (84%) and 354 (83%) respectively. Median follow up was 1095 days (median: 5 years, interquartile range: 1-10 years). During 3 years follow-up period, 59 (10%) in successful group and 18 (15%) patients in failure group died. Although successful revascularization of CTO was non-significantly associated with better outcome in total cohort (hazard ratio (HR): 0.593, 95% confidence interval (CI) 0.349-0.008, P: 0.054), it might be associated with lower risk of all-cause mortality (HR: 0.307, 95% CI 0.156-0.604, P: 0.001) and CV mortality (HR: 0.266, 95% CI 0.095-0.748, P: 0.012) in diabetics (P: 0.512). In contrast, successful CTO revascularization didn't improve outcomes in non-diabetics (all P > 0.05). In multivariate cox regression analysis, successful CTO revascularization remained an independent predictor for 3-years survival in diabetic subgroup (HR: 0.289, 95% CI 0.125-0.667, P: 0.004). The multivariate analysis result was similar after propensity score matching (all-cause mortality, HR: 0.348, 95% CI 0.142-0.851, P: 0.021). CONCLUSIONS: Successful CTO revascularization in diabetes may be related to better long term survival benefit but not in non-diabetic population.

Association of Ischemic Stroke, Major Bleeding, and Other Adverse Events With Warfarin Use vs Non-vitamin K Antagonist Oral Anticoagulant Use in Patients With Atrial Fibrillation With a History of Intracranial Hemorrhage.

Importance: Current guidelines recommend the use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF). Data regarding warfarin sodium use compared with NOAC use in patients with AF with a history of intracranial hemorrhage (ICH) are limited. Objective: To compare the clinical outcomes of warfarin use and NOAC use in patients with AF with a history of ICH using a nationwide cohort with AF. Design, Setting, and Participants: A nationwide cohort study from January 1, 2012, to December 31, 2016, was performed using data from the Taiwan National Health Insurance Research Database. The dates of analysis were July 1 to September 1, 2019. The study population comprised patients with AF with a history of ICH and a CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, prior stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease], age 65-74 years, sex category [female]) of at least 1 for men or at least 2 for women who had received warfarin or NOACs. The clinical outcomes were examined using Cox proportional hazards regression analyses among the study population before and after propensity score matching. Exposures: Oral anticoagulation with warfarin or NOACs. Main Outcomes and Measures: The clinical outcomes measured were all-cause mortality, ischemic stroke, ICH, major bleeding, and adverse events. Results: The study cohort included 4540 patients (mean [SD] age, 76.0 [10.5] years; 2653 men [58.4%]), with 1047 patients receiving warfarin (mean [SD] age, 75.1 [11.4] years; 571 men [54.5%]) and 3493 patients receiving NOACs (mean [SD] age, 76.3 [10.2] years; 2082 men [59.6%]). Compared with warfarin use, NOAC use was associated with statistically significantly lower risk of all-cause mortality (adjusted hazard ratio [aHR], 0.517; 95% CI, 0.457-0.585), ICH (aHR, 0.556; 95% CI, 0.389-0.796), and major bleeding (aHR, 0.645; 95% CI, 0.525-0.793), whereas the rate of ischemic stroke was similar in the 2 groups (aHR, 0.879; 95% CI, 0.678-1.141). These results were generally consistent after propensity score matching among 973 patients in each group. Conclusions and Relevance: Among patients with AF with prior ICH, NOAC use was associated with lower rates of ICH and major bleeding compared with warfarin use, whereas the rate of ischemic stroke was similar in the 2 groups. Among patients with AF with prior ICH, NOACs could be the preferred choice for stroke prevention.

Associations of antithrombotic agent use with clinical outcomes in critically ill patients with troponin I elevation in the absence of acute coronary syndrome.

INTRODUCTION: To evaluate efficacy of antithrombotic agents in critically ill patients with elevated troponin I level during intensive care unit (ICU) admission. METHODS AND RESULTS: It was a retrospective observational study which was conducted in a tertiary teaching hospital in Taipei, Taiwan. All patients hospitalized in ICU for >3 days and with available serum troponin I data from December 2015 to July 2017 were included. Patients with definite diagnosis of acute myocardial infarction (AMI) were excluded. We divided patients with troponin I elevation into three groups; no prescription, chronic prescription and new prescription of antithrombotic agents during ICU admission. We defined new prescription when patients were on antithrombotic agents, including antiplatelet agents, direct oral anticoagulants, and warfarin after troponin I was found to be elevated at ICU admission and chronic prescription, if antithrombotic agents were on medication list more than 30 days before ICU admission. Primary outcomes were 30-day and one-year all-cause mortality. Of 597 subjects who met inclusion criteria, 407 (68%) patients had elevated troponin I (>0.1 ng/mL) on ICU admission. These patients had increased 30-day [hazard ratio (HR), 1.679; 95% confidence interval (CI), 1.132-2.491; p = 0.009] and one-year (HR, 1.568; 95% CI, 1.180-2.083; p = 0.002) all-cause mortality compared with those without elevated troponin I. In patients with elevated troponin I, there was no significant difference of 30-day all-cause mortality among three groups (p = 0.051) whereas patients on chronic prescription showed significant survival benefit in one-year all-cause mortality when compared to those without or with new prescription (p = 0.008). CONCLUSIONS: In critically ill patients, elevated troponin I in the absence of AMI was associated with poor prognosis. Newly prescribed antithrombotic agents in ICU didn't reveal the difference in short and long-term prognosis while chronic antithrombotic agent use was associated with better one-year survival rate, suggesting that these drugs play a protective role in this high-risk population.

Association between asymmetric dimethylarginine and in-stent restenosis tissue characteristics assessed by optical coherence tomography.

BACKGROUND: Impaired bioavailability of endothelium-derived nitric oxide (NO) and endothelial dysfunction may play a pivotal role in the pathogenesis of in-stent restenosis (ISR) after coronary stenting. We aimed to investigate the relation between asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, and the ISR lesions tissue characteristics assessed by optical coherence tomography (OCT). METHODS AND RESULTS: Forty-five patients with symptomatic ISR lesions (17 bare metal stents, 28 drug-eluting stents, medium implantation duration: 58.0 months) were evaluated by OCT for in-stent tissue characteristics and calcification. We defined neoatherosclerosis as the presence of lipid or calcified neointima in ISR lesions, and 12 (26.7%), 33 (73.3%) ISR lesions were classified as with homogenous neointima and neoatherosclerosis respectively. The patients with neoatherosclerosis have significantly higher plasma ADMA levels compared to those of patients with homogenous neointima (1.12 ±â€¯0.21 µmol/l versus 0.83 ±â€¯0.08 µmol/l, p < 0.001). Furthermore, the plasma ADMA level of ISR lesions with intra-stent calcification (n = 24, 53.3%) was also significantly higher than those of ISR lesions without (n = 21, 46.7%; p < 0.001). There was a highly significant association between plasma ADMA level and intra-stent relative calcium index (mean calcium arc × calcium length)/(360 × analyzed length) (p < 0.001, r = 0.702). In multivariate analyses adjusted for age, sex, diabetes, eGFR, plasma ADMA level remained the only significant predictor for the presence of neoatherosclerosis (p = 0.008) and intra-stent calcification (p < 0.001). In contrast, plasma ADMA level correlated with intra-stent relative lipid core index (mean lipid core arc × lipid core length)/(360 × analyzed length) only in subgroup without intra-stent calcification (p = 0.004, r = 0.596, multivariate-adjusted p = 0.022). CONCLUSIONS: Increased plasma ADMA levels were associated with the development of in-stent neoatherosclerosis and calcification.