Safety and effectiveness of anticoagulation with non-vitamin K antagonist oral anticoagulants and warfarin in patients on tuberculosis treatment.

Anti-tuberculosis treatment can cause significant drug-drug interaction and interfere with effective anticoagulation. However, there is a lack of evidence and conflicting data on the optimal oral anticoagulation in patients treated for tuberculosis. We investigated the safety and effectiveness of anticoagulation with non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients on anti-tuberculosis treatment. Patients on concomitant oral anticoagulation and anti-tuberculosis treatment including rifampin were identified from the Korean nationwide healthcare database. Subjects were censored at discontinuation of either anticoagulation or rifampin. The outcomes of interest were major bleeding, death, and ischemic stroke. A total 2090 patients (1153 on warfarin, 937 on NOAC) were included. NOAC users, compared to warfarin users, were older, had a lower prevalence of hypertension, heart failure, ischemic stroke, and aspirin use and a higher prevalence of cancer, with no significant differences in CHA2DS2-VASc or HAS-BLED scores. There were 18 major bleeding events, 106 deaths, and 50 stroke events during a mean follow-up of 2.9 months. After multivariable adjustment, the use of NOAC was associated with a lower risk of incident ischemic stroke (HR 0.51, 95% CI 0.27-0.94), while there was no significant difference in risk for major bleeding or death compared with warfarin. These results suggest that NOACs have better effectiveness for stroke prevention and similar safety compared with warfarin in patients on concomitant anti-tuberculosis treatment. This is the first study assessing the safety and effectiveness of NOACs compared to warfarin in this clinical scenario.

Impact of Clinical and Lesion Features on Outcomes After Percutaneous Coronary Intervention in Bifurcation Lesions.

Background: Bifurcation percutaneous coronary intervention (PCI) is associated with higher risk of clinical events. Objectives: This study aimed to determine clinical and lesion features that predict adverse outcomes, and to evaluate the differential prognostic impact of these features in patients undergoing PCI for bifurcation lesions. Methods: We analyzed 5,537 patients from the BIFURCAT (comBined Insights From the Unified RAIN and COBIS bifurcAtion regisTries) registry. The primary outcome was major adverse cardiac events (MACE) at 2-year follow-up; secondary outcomes included hard endpoints (all-cause death, myocardial infarction) and lesion-oriented clinical outcomes (LOCO) (target-vessel myocardial infarction, target lesion revascularization). The least absolute shrinkage and selection operator (LASSO) model was used for feature selection. Results: During the 2-year follow-up period, MACE occurred in 492 patients (8.9%). The LASSO model identified 5 clinical features (old age, chronic renal disease, diabetes mellitus, current smoking, and left ventricular dysfunction) and 4 lesion features (left main disease, proximal main branch disease, side branch disease, and a small main branch diameter) as significant features that predict MACE. A combination of all 9 features improved the predictive value for MACE compared with clinical and lesion features (area under the receiver-operating characteristics curve: 0.657 vs 0.636 vs 0.581; P < 0.001). For secondary endpoints, the clinical features had a higher impact than lesion features on hard endpoints, whereas lesion features had a higher impact than clinical features on LOCO. Conclusions: In bifurcation PCI, 9 features were associated with MACE. Clinical features were predominant predictors for hard endpoints, and lesion features were predominant for predicting LOCO. Clinical and lesion features have distinct values, and both should be considered in bifurcation PCI.

Prediction of incident atherosclerotic cardiovascular disease with polygenic risk of metabolic disease: Analysis of 3 prospective cohort studies in Korea.

BACKGROUND AND AIMS: Studies have demonstrated that the risk of atherosclerotic cardiovascular disease (ASCVD) can be assessed by polygenic risk score (PRS) using common genetic variants. Because metabolic syndrome is a well-known, robust risk factor of ASCVD, we established PRS of metabolic disease and analyzed whether this PRS could predict incident ASCVD. METHODS: We constructed PRSs for eight quantifiable metabolic phenotypes-systolic/diastolic blood pressure, body mass index (BMI), four blood lipid components, and fasting blood glucose-by genome-wide association studies of two prospective Korean cohorts (n = 37,285). We conducted a grid search of combinations of metabolic PRSs to identify the most optimal weighted score for incident ASCVD (PRSMetS-ASCVD). The utility of PRSMetS-ASCVD was validated in an independent prospective cohort (n = 4333). RESULTS: The individuals in the highest PRS quintile demonstrated a 1.4-2.0-fold increased risk of incident hypertension, obesity, hyperlipidemia, and diabetes. Using the PRSMetS-ASCVD, we identified 6.7% of the population as a high risk group demonstrating a 3.3-fold (95% confidence interval 1.7-6.1, p < 0.001) higher risk for incident ASCVD. The model combining the PRSMetS-ASCVD demonstrated a better performance for predicting ASCVD than that consisting of only conventional risk factors, such as age, sex, BMI, smoking, hypertension, diabetes and hyperlipidemia. The population with high PRSMetS-ASCVD minimally overlapped with that of high Framingham risk score, thus suggesting the additive independent benefits beyond the Framingham risk score, especially in younger individuals. CONCLUSIONS: The polygenic risk of metabolic disease independently predicts those at an increased risk of ASCVD, identifying those at a genetically high risk of incident ASCVD.

Association Between Low Muscle Mass and Prognosis of Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

Background Low muscle mass has been associated with poor prognosis in certain chronic diseases, but its clinical significance in patients with coronary artery disease is unclear. We assessed the clinical significance of 2 easily measured surrogate markers of low muscle mass: the ratio of serum creatinine to serum cystatin C (Scr/Scys), and the ratio of estimated glomerular filtration rate by Scys to Scr (eGFRcys/eGFRcr). Methods and Results Patients with coronary artery disease undergoing percutaneous coronary intervention were prospectively enrolled from a single tertiary center, and Scr and Scys levels were simultaneously measured at admission. Best cut-off values for Scr/Scys and eGFRcys/eGFRcr to discriminate 3-year mortality were determined; 1.0 for men and 0.8 for women in Scr/Scys, and 1.1 for men and 1.0 for women in eGFRcys/eGFRcr. The prognostic values on 3-year mortality and the additive values of 2 markers on the predictive model were compared. In 1928 patients enrolled (mean age 65.2±9.9 years, 70.8% men), the risk of 3-year mortality increased proportionally according to the decrease of the surrogate markers. Both Scr/Scys- and eGFRcys/eGFRcr-based low muscle mass groups showed significantly higher risk of death, after adjusting for possible confounders. They also increased predictive power of the mortality prediction model. Low Scr/Scys values were associated with high mortality rate in patients who were ≥65 years, nonobese, male, had renal dysfunction at baseline, and presented with acute myocardial infarction. Conclusions Serum surrogate markers of muscle mass, Scr/Scys, and eGFRcys/eGFRcr may have clinical significance for detecting patients with coronary artery disease at high risk for long-term mortality.

Circulating tumor DNA as a prognostic indicator in resectable pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

Circulating tumor DNA (ctDNA) is a promising prognostic biomarker in various cancers. Due to the high recurrence rate of resectable pancreatic ductal adenocarcinoma (PDAC), effective strategies for prognostic stratification are necessary. Yet, for resectable PDAC, prognostic impact of ctDNA lacks systemic evidence. We sought to investigate the prognostic significance of baseline ctDNA and postoperative ctDNA in patients with resectable PDAC. PubMed, EMBASE, and the Cochrane library were searched up to March 2019. Five studies met the inclusion criteria, and 375 patients were pooled for the meta-analysis. Positive ctDNA significantly indicated poor overall survival (at baseline, hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.13-4.56; postoperative, HR 3.66, 95% CI 1.45-9.28). Patients with detectable ctDNA showed the trend to have higher risk for disease recurrence than those without detectable ctDNA (at baseline, HR 1.96, 95% CI 0.65-5.87; postoperative, HR 2.20, 95% CI 0.99-4.87). The results were consistent regardless of pre- or post-operative ctDNA. There was no significant heterogeneity among the included studies. In conclusion, our meta-analysis revealed that ctDNA, either at baseline or postoperative, might be a useful prognostic biomarker for stratifying risk of death and recurrence in resectable PDAC.

Diagnostic Agreement of Quantitative Flow Ratio With Fractional Flow Reserve and Instantaneous Wave-Free Ratio.

Background Quantitative flow ratio ( QFR ) has a high diagnostic accuracy in assessing functional stenoses relevance, as judged by fractional flow reserve ( FFR ). However, its diagnostic performance has not been thoroughly evaluated using instantaneous wave-free ratio ( iFR ) or coronary flow reserve as the reference standard. This study sought to evaluate the diagnostic performance of QFR using other reference standards beyond FFR . Methods and Results We analyzed 182 patients (253 vessels) with stable ischemic heart disease and 82 patients (105 nonculprit vessels) with acute myocardial infarction in whom coronary stenoses were assessed with FFR , iFR, and coronary flow reserve. Contrast QFR analysis of interrogated vessels was performed in blinded fashion by a core laboratory, and its diagnostic performance was evaluated with respect to the other invasive physiological indices. Mean percentage diameter stenosis, FFR , iFR , coronary flow reserve, and QFR were 53.1±19.0%, 0.80±0.13, 0.88±0.12, 3.14±1.30, and 0.81±0.14, respectively. QFR showed higher correlation ( r=0.863 with FFR versus 0.740 with iFR , P<0.001), diagnostic accuracy (90.8% versus 81.3%, P<0.001), and discriminant function (area under the curve=0.953 versus 0.880, P<0.001) when FFR was used as a reference standard than when iFR was used as the reference standard. However, when coronary flow reserve was used as an independent reference standard, FFR , iFR , and QFR showed modest discriminant function (area under the curve=0.682, 0.765, and 0.677, respectively) and there were no significant differences in diagnostic accuracy among FFR , iFR , and QFR (65.4%, 70.6%, and 64.9%; all P values in pairwise comparisons >0.05, overall comparison P=0.061). Conclusions QFR has a high correlation and agreement with respect to both FFR and iFR , although it is better when FFR is used as the comparator. As a pressure-derived index not depending on wire or adenosine, QFR might be a promising tool for improving the adoption rate of physiology-based revascularization in clinical practice.

The Effects of Preoperative Aspirin on Coronary Artery Bypass Surgery: a Systematic Meta-Analysis.

BACKGROUND AND OBJECTIVES: Aspirin plays an important role in the maintenance of graft patency and the prevention of thrombotic event after coronary artery bypass graft surgery (CABG). However, the use of preoperative aspirin is still under debate due to the risk of bleeding. METHODS: From PubMed, EMBASE, and Cochrane Central Register of Controlled Trials, data were extracted by 2 independent reviewers. Meta-analysis using random effect model was performed. RESULTS: We performed a systemic meta-analysis of 17 studies (12 randomized controlled studies and 5 non-randomized registries) which compared clinical outcomes of 9,101 patients who underwent CABG with or without preoperative aspirin administration. Preoperative aspirin increased chest tube drainage (weighted mean difference 177.4 mL, 95% confidence interval [CI], 41.3-313.4; p=0.011). However, the risk of re-operation for bleeding was not different between the preoperative aspirin group and the control group (3.2% vs. 2.4%; odds ratio [OR], 1.23; 95% CI, 0.94-1.60; p=0.102). There was no difference in the rates of all-cause mortality (1.6% vs. 1.5%; OR, 0.98; 95% CI, 0.64-1.49; p=0.920) and myocardial infarction (MI) (8.7% vs. 10.4%; OR, 0.83; 95% CI, 0.66-1.04; p=0.102) between patients with and without preoperative aspirin administration. CONCLUSIONS: Although aspirin increased the amount of chest tube drainage, it was not associated with increased risk of re-operation for bleeding. In addition, the risks of early postoperative all-cause mortality and MI were not reduced by using preoperative aspirin.

Influence of Sex on Relationship Between Total Anatomical and Physiologic Disease Burdens and Their Prognostic Implications in Patients With Coronary Artery Disease.

Background Total atherosclerosis disease burden is associated with clinical outcomes in patients with coronary artery disease. However, the influence of sex on the relationship between total anatomical and physiologic disease burdens and their prognostic implications have not been well defined. Methods and Results A total of 1136 patients who underwent fractional flow reserve (FFR) measurement in all 3 major coronary arteries were included in this study. Anatomical and physiologic total disease burden was assessed by SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score, residual SYNTAX score, a total sum of FFR in 3 vessels (3-vessel FFR), and functional SYNTAX score. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization at 2 years. There were no differences in angiographic diameter stenosis, SYNTAX score, or residual SYNTAX score between women and men. However, both per-vessel FFR (0.89±0.10 versus 0.87±0.11, P<0.001) and 3-vessel FFR (2.72±0.13 versus 2.69±0.15, P<0.001) were higher in women. Multivariable Cox regression analyses showed that total anatomical and physiologic disease burdens were significantly associated with 2-year major adverse cardiac events, and there was no significant interaction between sex and total disease burden for clinical outcomes. Conclusions Despite similar angiographic disease severity, both per-vessel and per-patient physiologic disease severity was less in women than in men. There was no influence of sex on prognostic implications of total anatomical and physiologic disease burdens in patients with coronary artery disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01621438.

Comparison of long-term clinical outcomes between revascularization versus medical treatment in patients with silent myocardial ischemia.

BACKGROUND: There have been limited and conflicting results regarding the prognostic impact of revascularization treatment on the long-term clinical outcomes of silent ischemia. The current study aimed to determine whether revascularization treatment compared with medical treatment (MT) alone reduces long-term risk of cardiac death of asymptomatic patients with objective evidence of inducible myocardial ischemia. METHODS: A total of 1473 consecutive asymptomatic patients with evidence of inducible myocardial ischemia were selected from a prospective institutional registry. All patients showed at least 1 epicardial coronary stenosis with ≥50% diameter stenosis in coronary angiography. Patients were classified according to their treatment strategies. The primary outcome was cardiac death up to 10 years. RESULTS: Among the total population, 709 patients (48.1%) received revascularization treatment including percutaneous coronary intervention (PCI, n = 558) or coronary artery bypass graft surgery (CABG, n = 151), with the remaining patients (764 patients, 51.9%) receiving MT alone. During the follow-up period, the revascularization treatment group showed a significantly lower risk of cardiac death compared with the MT alone group (25.4% vs. 33.7%, HR 0.624, 95%CI 0.498-0.781, p < 0.001). Among revascularized patients, patients with negative non-invasive stress test results after revascularization showed significantly lower risk of cardiac death compared to those with residual myocardial ischemia (8.9% vs. 18.7%, HR 0.406, 95% CI 0.175-0.942, p = 0.036). CONCLUSIONS: In patients with silent myocardial ischemia, revascularization treatment was associated with significantly lower long-term risk of cardiac death compared with the MT alone group. The current results support contemporary practice of ischemia-directed revascularization, even in patients with silent myocardial ischemia.

Addition of Hyperbaric Oxygen Therapy vs Medical Therapy Alone for Idiopathic Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-analysis.

Importance: Sudden sensorineural hearing loss (SSNHL) causes substantial disease burden for both individuals and socioeconomic aspects. The benefit of hyperbaric oxygen therapy (HBOT) in addition to standard medical therapy (MT) for idiopathic SSNHL has been unclear. Objective: To perform a systematic review and meta-analysis to compare HBOT + MT with MT alone as a treatment for patients with SSNHL. Data Sources: PubMed, Embase, and the Cochrane Database of Systematic Reviews were systematically searched up to February 2018. Study Selection: Randomized clinical trials and nonrandomized studies comparing HBOT + MT with MT alone for SSNHL treatment. Data Extraction and Synthesis: Two investigators independently screened the eligible studies, established data, and assessed quality and risk of bias. A systematic review and meta-analysis using random-effects models was conducted. Main Outcomes and Measures: The primary outcome was complete hearing recovery, and secondary outcomes were any hearing recovery and absolute hearing gain. Results: Three randomized clinical trials and 16 nonrandomized studies comparing outcomes after HBOT + MT vs MT alone in 2401 patients with SSNHL (mean age, 45.4 years; 55.3% female) were included. Pooled odds ratios (ORs) for complete hearing recovery and any hearing recovery were significantly higher in the HBOT + MT group than in the MT alone group (complete hearing recovery OR, 1.61; 95% CI, 1.05-2.44 and any hearing recovery OR, 1.43; 95% CI, 1.20-1.67). Absolute hearing gain was also significantly greater in the HBOT + MT group than in the MT alone group. The benefit of HBOT was greater in groups with severe to profound hearing loss at baseline, HBOT as a salvage treatment, and a total HBOT duration of at least 1200 minutes. Conclusions and Relevance: The addition of HBOT to standard MT is a reasonable treatment option for SSNHL, particularly for those patients with severe to profound hearing loss at baseline and those who undergo HBOT as a salvage treatment with a prolonged duration. Optimal criteria for patient selection and a standardized regimen for HBOT should be applied in routine practice, with future trials to investigate maximal treatment benefit.

Association between aortic knob width and invasively measured aortic pulse pressure.

BACKGROUND: Aortic knob width (AKW), which can be measured easily in simple radiography, is associated with the degree of dilatation and tortuosity of the aortic arch. Pulsatile stress influences aortic geometry. This study was carried out to investigate whether AKW can represent invasively measured aortic pulse pressure (APP). METHODS: A total of 252 patients who underwent invasive coronary angiography (ICA) for the evaluation of coronary artery disease were enrolled. AKW was defined as the perpendicular length from the lateral margin of the main bronchus to the most prominent edge of the aortic knob on chest radiography. APP was measured at the ascending aorta using a pigtail catheter immediately before ICA. RESULTS: When patients were divided into two groups according to the median value of APP (69 mmHg), AKW was significantly greater in patients with higher APP (≥69 mmHg) than in those with lower APP (<69 mmHg) (40.6±4.9 vs. 38.1±4.2 mm, P<0.001). There was a positive linear correlation between APP and AKW (r=0.207, P<0.001). In multiple linear regression analysis, the significant association between APP and AKW remained even after controlling for the confounding factors, including age, sex, height, heart rate, smoking status, left ventricular ejection fraction, and left ventricular end-diastolic dimension (ß=0.131, P=0.031). CONCLUSION: Greater AKW on chest radiography was independently predictive of increased APP in patients undergoing elective ICA. The results of this study suggest that AKW can be useful as a simple surrogate marker of APP.

Differential Clinical Outcomes Between Angiographic Complete Versus Incomplete Coronary Revascularization, According to the Presence of Chronic Kidney Disease in the Drug-Eluting Stent Era.

BACKGROUND: There are limited data regarding the prognostic impact of angiographic complete revascularization (CR) in patients with chronic kidney disease (CKD). We sought to investigate the differential prognostic impact of angiographic CR over incomplete revascularization (IR), according to the presence of CKD in the drug-eluting stent era. METHODS AND RESULTS: Between 2003 and 2011 at Samsung Medical Center, consecutive patients with multivessel disease were stratified by the presence of CKD (estimated glomerular filtration rate <60 mL/min per 1.73 m2) and classified according to angiographic CR (residual SYNTAX score=0) or IR. Clinical outcomes were compared between angiographic CR and IR, stratified by the presence of CKD. Primary outcome was patient-oriented composite outcomes (POCO, a composite of all-cause death, myocardial infarction, any revascularization) at 3 years. Inverse probability weighting was performed between the CR and IR groups. A total of 3224 patients were eligible for analysis: 2295 without CKD; 929 with CKD. Among non-CKD patients, angiographic CR showed a significantly lower risk of POCO than IR (17.2% versus 21.7%, adjusted hazard ratio 0.76, 95% confidence interval, 0.62-0.95, P=0.014), mainly driven by a significantly lower risk of any revascularization. Among CKD patients, however, angiographic CR was associated with a significantly higher risk of POCO than IR (37.7% versus 28.4%, adjusted hazard ratio 1.42, 95% confidence interval, 1.08%-1.85%, P=0.011), mainly driven by a significantly higher risk of nonfatal target vessel myocardial infarction. CONCLUSIONS: Angiographic CR was associated with reduced risk of POCO than IR in patients without CKD; however, it was associated with a significantly higher risk of POCO and nonfatal myocardial infarction in CKD patients.

Prognostic Implication of Functional Incomplete Revascularization and Residual Functional SYNTAX Score in Patients With Coronary Artery Disease.

OBJECTIVES: The aim of this study was to investigate the prognostic implication of functional incomplete revascularization (IR) and residual functional SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (rFSS) in comparison with 3-vessel fractional flow reserve (FFR) and residual SYNTAX score. BACKGROUND: IR is associated with poor clinical outcomes in patients who underwent percutaneous coronary intervention. METHODS: A total of 385 patients who underwent 3-vessel FFR measurement after stent implantation were included in this study. The rFSS was defined as residual SYNTAX score measured only in vessels with FFR ≤0.8. The study population was divided into the functional IR group (rFSS ≥1) and the functional complete revascularization (CR) group (rFSS = 0). The primary outcome was major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization) at 2 years. RESULTS: Functional CR was achieved in 283 patients (73.5%). At 2-year follow-up, the functional IR group showed a significantly higher risk for MACEs (functional IR vs. CR, 14.6% vs. 4.2%; hazard ratio: 4.09; 95% confidence interval: 1.82 to 9.21; p < 0.001) than the functional CR group. In a multivariate-adjusted model, functional IR was an independent predictor of MACEs (adjusted hazard ratio: 4.17; 95% confidence interval: 1.85 to 9.44; p < 0.001). The rFSS showed a significant association with estimated 2-year MACE rate (hazard ratio: 1.09 per 1-U increase; 95% confidence interval: 1.02 to 1.17; p = 0.018). When added to clinical risk factors, rFSS showed the highest integrated discrimination improvement value for MACEs (3.5%; p = 0.002) among 3-vessel FFR, residual SYNTAX score, and rFSS. CONCLUSIONS: Patients with functional IR showed significantly higher rate of 2-year MACEs than those with functional CR. A combined anatomic and physiological scoring system (rFSS) after stent implantation better discriminated the risk for adverse events than anatomic or physiological assessment alone. (Clinical Implication of 3-Vessel Fractional Flow Reserve [FFR]; NCT01621438).

Proteinuria Detected by Urine Dipstick Test as a Risk Factor for Atrial Fibrillation: A Nationwide Population-Based Study.

Proteinuria is one of the well-known risk factors for cardiovascular disease. However the impact of proteinuria on the incidence of atrial fibrillation (AF) is unclear. In this study, we investigated the association between proteinuria detected using urine dipstick test and the risk of AF. A total of 18,201,275 individuals were analyzed, who had no prior AF and had received biennial health checkups provided by the National Health Insurance Service between 2005 and 2008 in Korea. Incidences of AF were ascertained through the end of 2015. During a mean follow-up of 9.6 years, a total of 324,764 (1.8%) developed AF (1.86 per 1,000 person-years). In Cox regression models, proteinuria was associated with an increased risk of AF: adjusted HR and 95% CI of AF occurrence were 1.13 (1.10-1.16), 1.34 (1.31-1.38), 1.53 (1.48-1.58), 1.82 (1.71-1.94), and 1.86 (1.61-2.16) in individuals with trace, 1+, 2+, 3+, and 4+ proteinuria, respectively, compared with those without proteinuria. The result was consistent even after additional adjustment for estimated glomerular filtration rate. In addition, the risk of AF further increased or decreased according to the follow-up dipstick test results. Thus, proteinuria measured with a dipstick test might be considered a potent risk factor for AF development.