Background: Data regarding the association between preexisting cardiovascular risk factors (CVRFs) and cardiovascular diseases (CVDs) and the outcomes of patients requiring hospitalization for coronavirus disease 2019 (COVID-19) are limited. Therefore, the aim of this study was to investigate the impact of preexisting CVRFs or CVDs on the outcomes of patients with COVID-19 hospitalized in a Korean healthcare system. Methods: Patients with COVID-19 admitted to 10 hospitals in Daegu Metropolitan City, Korea, were examined. All sequentially hospitalized patients between February 15, 2020, and April 24, 2020, were enrolled in this study. All patients were confirmed to have COVID-19 based on the positive results on the polymerase chain reaction testing of nasopharyngeal samples. Clinical outcomes during hospitalization, such as requiring intensive care and invasive mechanical ventilation (MV) and death, were evaluated. Moreover, data on baseline comorbidities such as a history of diabetes, hypertension, dyslipidemia, current smoking, heart failure, coronary artery disease, cerebrovascular accidents, and other chronic cardiac diseases were obtained. Results: Of all the patients enrolled, 954 (42.0%) had preexisting CVRFs or CVDs. Among the CVRFs, the most common were hypertension (28.8%) and diabetes mellitus (17.0%). The prevalence rates of preexisting CVRFs or CVDs increased with age (P < 0.001). The number of patients requiring intensive care (P < 0.001) and invasive MV (P < 0.001) increased with age.The in-hospital death rate increased with age (P < 0.001). Patients requiring intensive care (5.3% vs. 1.6%; P < 0.001) and invasive MV (4.3% vs. 1.7%; P < 0.001) were significantly greater in patients with preexisting CVRFs or CVDs. In-hospital mortality (12.9% vs. 3.1%; P < 0.001) was significantly higher in patients with preexisting CVRFs or CVDs. Among the CVRFs, diabetes mellitus and hypertension were associated with increased requirement of intensive care and invasive MV and in-hospital death. Among the known CVDs, coronary artery disease and congestive heart failure were associated with invasive MV and in-hospital death. In multivariate analysis, preexisting CVRFs or CVDs (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.07–3.01; P = 0.027) were independent predictors of in-hospital death adjusting for confounding variables. Among individual preexisting CVRF or CVD components, diabetes mellitus (OR, 2.43; 95% CI, 1.51–3.90; P < 0.001) and congestive heart failure (OR, 2.43; 95% CI, 1.06–5.87; P = 0.049) were independent predictors of in-hospital death. Conclusion Based on the findings of this study, the patients with confirmed COVID-19 with preexisting CVRFs or CVDs had worse clinical outcomes. Caution is required in dealing with these patients at triage.after

Background/Aims: Minimising total ischemic time (TIT) is important for improving clinical outcomes in patients with ST-segment elevation myocardial infarction who have undergone percutaneous coronary intervention (PCI). TIT has not shown a significant improvement due to persistent pre-hospital delay. This study aimed to investigate the risk factors associated with pre-hospital delay. Methods: Individuals enrolled in the Korea Acute Myocardial Infarction Registry-National Institutes of Health between 2011 and 2015 were included in this study. The study population was analyzed according to the symptom-to-door time (STDT; within 60 or > 60 minutes), and according to the type of hospital visit (emergency medical services [EMS], non-PCI center, or PCI center). Results: A total of 4,874 patients were included in the analysis, of whom 28.4% arrived at the hospital within 60 minutes of symptom-onset. Old age (> 65 years), female gender, and renewed ischemia were independent predictors of delayed STDT. Utilising EMS was the only factor shown to reduce STDT within 60 minutes, even when cardiogenic shock was evident. The overall frequency of EMS utilisation was low (21.7%). Female gender was associated with not utilising EMS, whereas cardiogenic shock, previous myocardial infarction, familial history of ischemic heart disease, and off-hour visits were associated with utilising EMS. Conclusions Factors associated with delayed STDT and not utilising EMS could be targets for preventive intervention to improve STDT and TIT.

Background: This study aimed to investigate the incidences of and risk factors for perioperative events following anticoagulant discontinuation in patients with non-valvular atrial fibrillation (NVAF) undergoing non-cardiac surgery. Methods: A total of 216 consecutive patients who underwent cardiac consultation for suspending perioperative anticoagulants were enrolled. A perioperative event was defined as a composite of thromboembolism and major bleeding. Results: The mean anticoagulant discontinuation duration was 5.7 (±4.2) days and was significantly longer in the warfarin group (p<0.001). Four perioperative thromboembolic (1.85%; three strokes and one systemic embolization) and three major bleeding events (1.39%) were observed. The high CHA2DS2-VASc and HAS-BLED scores and a prolonged preoperative anticoagulant discontinuation duration (4.4±2.1 vs. 2.9±1.8 days; p=0.028) were associated with perioperative events, whereas the anticoagulant type (non-vitamin K antagonist oral anticoagulants or warfarin) was not. The best cut-off levels of the HAS-BLED and CHA2DS2-VASc scores were 3.5 and 2.5, respectively, and the preoperative anticoagulant discontinuation duration for predicting perioperative events was 2.5 days. Significant differences in the perioperative event rates were observed among the four risk groups categorized according to the sum of these values: risk 0, 0%; risk 1, 0%; risk 2, 5.9%; and risk 3, 50.0% (p<0.001). Multivariate logistic regression analysis showed that the HAS-BLED score was an independent predictor for perioperative events. Conclusion Thromboembolic events and major bleeding are not uncommon during perioperative anticoagulant discontinuation in patients with NVAF, and interrupted anticoagulation strategies are needed to minimize these.

A 60-year-old male patient with coronavirus disease-2019 showed new onset ST-segment elevation in V1–V2 leads on electrocardiogram and cardiac enzyme elevation in intensive care unit. He had a history of type 2 diabetes mellitus, hypertension, and dyslipidemia. He was receiving mechanical ventilation and veno-venous extracorporeal membrane oxygenation treatment for severe hypoxia. Two-D echocardiogram showed regional wall motion abnormalities. We performed primary percutaneous coronary intervention for acute myocardial infarction complicating cardiogenic shock under hemodynamic support. He expired on the 16th day of admission because of cardiogenic shock and multi-organ failure. Active surveillance and intensive treatment strategy are important for saving lives of COVID-19 patients with acute myocardial infarction.

Background: The association of N-terminal pro-B type natriuretic peptide (NT-proBNP) and plasma renin activity (PRA) for the prognosis of the patients with acute heart failure (HF) has not been fully investigated. This study aimed to determine the association between NT-proBNP and PRA and to investigate the incremental value of PRA to NT-proBNP for predicting long term prognosis in patients with acute HF. Methods: Three hundred and ninety-six patients (mean age, 64.7 ± 15.9 years; 46.5% female) presenting with acute HF were enrolled between December 2004 and July 2013. Patients with newly diagnosed HF as well as patients with acute exacerbated chronic HF were included. The prognosis was assessed with the composite event of all-cause mortality and readmission for HF during a 2-year follow-up period. Results: The etiology of HF was ischemic in 116 (29.3%) patients. In a Cox proportional hazards model, log-transformed PRA (hazard ratio [HR], 1.205; P = 0.007) was an independent predictor of the composite outcome of all-cause mortality and readmission for HF in addition to age (HR, 1.032; P = 0.001), white blood cell (WBC) count (HR, 1.103;P< 0.001), and left ventricular ejection fraction (LVEF) (HR, 0.978; P = 0.013). Adding PRA to age, sex, LVEF, and NT-proBNP significantly improved the prediction for the composite outcome of all-cause mortality and readmission for HF, as shown by the net reclassification improvement (0.47; P < 0.001) and integrated discrimination improvement (0.10; P < 0.001). Conclusion PRA could provide incremental predictive value to NT-proBNP for predicting long term prognosis in patients with acute HF.

BACKGROUND/AIMS: Carbohydrate antigen 125 (CA-125) is an emerging prognostic biomarker for heart failure. We aimed to test the long-term prognostic value of CA-125 in combination with N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with acute decompensated heart failure (ADHF). METHODS: This observational study included a total of 413 patients (64.1 ± 15.6 year-old, 214 men) with ADHF. All-cause mortality during the 2-year follow-up was investigated for the prognosis. RESULTS: During the follow-up (mean follow-up, 591 ± 233 days), 109 deaths (26.0%) were recorded. In the multivariable analysis model, CA-125 was an independent factor associated with all-cause mortality (log CA-125: hazard ratio, 1.23; 95% confidence interval, 1.02 to 1.48; p = 0.030) together with age, sex, New York Heart Association class, β-blocker, and NT-proBNP. The Kaplan-Meier survival analysis demonstrated that the group with both low marker levels showed the best 2-year survival (87.9%) followed by the group with low NT-proBNP and high CA-125 (76.1%), high NT-proBNP and low CA-125 (64.7%) and high NT-proBNP and high CA-125 levels (54.3%) (p < 0.001). Addition of CA-125 in combination with NT-proBNP and established risk factors further increased the predictive power for mortality in patients with ADHF. CONCLUSIONS CA-125 was an independent factor associated with all-cause mortality in patients with ADHF. Combination of CA-125 with NT-proBNP significantly improved the prediction of mortality in patients with ADHF.

Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101. To support clinical development, we also evaluated the preclinical pharmacokinetics and toxicokinetics in cynomolgus monkeys, and human and cynomolgus monkey tissue was stained with YYB-101 to test tissue cross-reactivity. We found that YYB-101 inhibited cMET activation in vitro and suppressed tumor growth in the orthotopic mouse model of human glioblastoma. Combination treatment with YYB-101 and temozolomide decreased tumor growth and increased overall survival compared with the effects of either agent alone. Five cancer-related genes (TMEM119, FST, RSPO3, ROS1 and NBL1) were overexpressed in YYB-101-treated mice that showed tumor regrowth. In the tissue cross-reactivity assay, critical cross-reactivity was not observed. The terminal elimination half-life was 21.7 days. Taken together, the in vitro and in vivo data demonstrated the anti-tumor efficacy of YYB-101, which appeared to be mediated by blocking the HGF/cMET interaction. The preclinical pharmacokinetics, toxicokinetics and tissue cross-reactivity data support the clinical development of YYB-101 for advanced cancer.
Animals ; Antibodies, Neutralizing* ; Cell Line ; Cell Proliferation ; Glioblastoma ; Half-Life ; Hepatocyte Growth Factor ; Heterografts ; Humans* ; In Vitro Techniques ; Macaca fascicularis ; Mice ; Mice, Nude ; Pharmacokinetics ; Phosphorylation ; Phosphotransferases ; Toxicokinetics

The prevalence of heart failure (HF) is skyrocketing worldwide, and is closely associated with serious morbidity and mortality. In particular, HF is one of the main causes for the hospitalization and mortality in elderly individuals. Korea also has these epidemiological problems, and HF is responsible for huge socioeconomic burden. However, there has been no clinical guideline for HF management in Korea. 
The present guideline provides the first set of practical guidelines for the management of HF in Korea and was developed using the guideline adaptation process while including as many data from Korean studies as possible. The scope of the present guideline includes the definition, diagnosis, and treatment of chronic HF with reduced/preserved ejection fraction of various etiologies.
Aged ; Diagnosis* ; Heart Failure* ; Heart* ; Hospitalization ; Humans ; Korea ; Mortality ; Prevalence

BACKGROUND AND OBJECTIVES: Optimal international normalized ratio (INR) in elderly atrial fibrillation (AF) patients at higher risk of hemorrhagic events remains unclear. We investigated the efficacy and safety of low-intensity warfarin therapy (target international normalized ratio [INR], 1.6-2.6) in elderly Korean patients with nonvalvular AF (NVAF). SUBJECTS AND METHODS: We enrolled 528 NVAF patients (mean age, 67±9 years; 361 men) who were actively taking warfarin. Major events were defined based on the annual rates of ischemic stroke, systemic embolism, and major bleeding events requiring blood transfusion or hospitalization. Time in therapeutic range (TTR) was 45±19% for all patients. RESULTS: Ischemic stroke and systemic embolism occurred in 20 patients with INR between 1.00 and 2.44 (16 ischemic strokes and 4 systemic embolisms) and major bleeding in 37 patients with INR between 1.74 and no coagulation (exceed laboratory detection capability, more than 10 [7 intracranial hemorrhages, 21 gastrointestinal bleedings, and 9 others]). Incidence rates of ischemic or hemorrhagic events at INR<2.00, 2-3, and >3 were 3.0%, 1.4%, and 20.1% per year, respectively. In patients who were ≥70 years old, CHADS₂, CHA₂DS₂VASc, and HAS-BLED scores were significantly higher compared with those in patients who were <70 years old. When we applied the INR between 1.6 and 2.6, as recommended by the Japanese AF Guideline for patients≥70 years old, the TTR increased from 43.8% to 58.6%. In addition, ischemic or hemorrhagic event rates decreased from 1.9% to 1.2% within the optimal INR range. CONCLUSION: Low-intensity warfarin therapy (INR, 1.6-2.6) should be considered in elderly Korean patients with NVAF.
Aged* ; Asian Continental Ancestry Group ; Atrial Fibrillation* ; Blood Transfusion ; Embolism ; Hemorrhage ; Hospitalization ; Humans ; Incidence ; International Normalized Ratio* ; Intracranial Hemorrhages ; Stroke ; Warfarin*

Cardiac involvement is a major cause of morbidity and mortality in hypereosinophilic syndrome (HES). It is classified into 3 stages by the degree of eosinophils-mediated heart injury; acute necrotic stage, thrombotic stage, and fibrotic stage. Nonetheless, definitive evidence that each patient passes sequentially through these stages is lacking. We present a case of 48-year-old male patient with dyspnea and peripheral edema who underwent valve replacement surgery due to severe mitral regurgitation. After the valve replacement, HES with cardiac involvement in the thrombotic stage was diagnosed. In the follow-up study, the patient progressed into fibrotic stage of HES.
Dyspnea ; Edema ; Follow-Up Studies ; Heart Injuries ; Humans ; Hypereosinophilic Syndrome* ; Male ; Middle Aged ; Mitral Valve Insufficiency ; Mortality