Net clinical benefit of oral anticoagulants in Korean atrial fibrillation patients with low to intermediate stroke risk: A report from the Clinical Survey on Stroke Prevention in patients with Atrial Fibrillation (CS-SPAF).

Background: The balance of stroke risk reduction and potential bleeding risk associated with antithrombotic treatment (ATT) remains unclear in atrial fibrillation (AF) at non-gender CHA2DS2-VASc scores 0-1. A net clinical benefit (NCB) analysis of ATT may guide stroke prevention strategies in AF with non-gender CHA2DS2-VASc scores 0-1. Methods: This multi-center cohort study evaluated the clinical outcomes of treatment with a single antiplatelet (SAPT), vitamin K antagonist (VKA), and non-VKA oral anticoagulant (NOAC) in non-gender CHA2DS2-VASc score 0-1 and further stratified by biomarker-based ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/mL], creatinine clearance [<50 mL/min], and dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT, including composite thrombotic events (ischemic stroke, systemic embolism, and myocardial infarction) and major bleeding events. Results: We included 2465 patients (age 56.2 ± 9.5 years; female 27.0%) followed-up for 4.0 ± 2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. With detailed risk stratification using the ABCD score, NOAC showed a significant positive NCB compared with the other ATTs (SAPT vs. NOAC, NCB 2.01, 95% confidence interval [CI] 0.37-4.66; VKA vs. NOAC, NCB 2.38, 95% CI 0.56-5.40) in ABCD score ≥1. ATT failed to show a positive NCB in patients with truly low stroke risk (ABCD score = 0). Conclusions: In the Korean AF cohort at non-gender CHA2DS2-VASc scores 0-1, NOAC showed significant NCB advantages over VKA or SAPT with ABCD score ≥1.

CoAt-Mixer: Self-attention deep learning framework for left ventricular hypertrophy using electrocardiography.

Left ventricular hypertrophy is a significant independent risk factor for all-cause mortality and morbidity, and an accurate diagnosis at an early stage of heart change is clinically significant. Electrocardiography is the most convenient, economical, and non-invasive method for screening in primary care. However, the coincidence rate of the actual left ventricular hypertrophy and diagnostic findings was low, consequently increasing the interest in algorithms using big data and deep learning. We attempted to diagnose left ventricular hypertrophy using big data and deep learning algorithms, and aimed to confirm its diagnostic power according to the differences between males and females. This retrospective study used electrocardiographs obtained at Yonsei University Wonju Severance Christian Hospital, Wonju, Korea, from October 2010 to February 2020. Binary classification was performed for primary screening for left ventricular hypertrophy. Three datasets were used for the experiment: the male, female, and entire dataset. A cutoff for binary classification was defined as the meaningful as a screening test (<132 g/m2 vs. ≥132 g/m2, <109 g/m2 vs. ≥109 g/m2). Six types of input were used for the classification tasks. We attempted to determine whether electrocardiography had predictive power for left ventricular hypertrophy diagnosis. For the entire dataset, the model achieved an area under the receiver operating characteristic (AUROC) curve of 0.836 (95% CI, 0.833-838) with a sensitivity of 78.37% (95% CI, 76.79-79.95). For the male dataset, the AUROC was 0.826 (95% CI, 0.822-830) with a sensitivity of 76.73% (95% CI, 75.14-78.33). For the female dataset, the AUROC was 0.772 (95% CI, 0.769-775) with a sensitivity of 72.90% (95% CI, 70.33-75.46). Our model confirmed that left ventricular hypertrophy can be classified to some extent using electrocardiography, demographics, and electrocardiography features. In particular, a learning environment that considered gender differences was constructed. Consequently, the difference in diagnostic power between men and women was confirmed. Our model will help patients with suspected left ventricular hypertrophy to undergo screening tests at a low cost. In addition, our research and attempts will show the expected effect that gender-consideration approaches can help with various currently proposed diagnostic methods.

Impact of the ultra-long 48 mm drug-eluting stent on procedural and clinical outcomes in patients with diffuse long coronary artery disease.

BACKGROUND: Diffuse coronary artery disease (CAD) is a prognostic factor after percutaneous coronary intervention (PCI) and requires multiple overlapping stent implantations. HYPOTHESIS: We investigated the impact of ultra-long 48 mm drug-eluting stent (DES) on procedural and clinical outcomes in real-world practice. METHODS: Patients who underwent DES implantation for a lesion length of >40 mm were selected from a prospective registry between 2019 and 2021. Patients treated with one or more ultra-long 48 mm DES were in the ultra-long DES group (n = 221). The others comprised the conventional DES group (n = 428). Procedural and clinical outcomes were compared after propensity score matching (PSM). The primary endpoint was a device-oriented composite outcome (DOCO) consisting of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization at 1-year follow-up. RESULTS: After PSM, 158 matched pairs of patients showed no differences in the baseline clinical and angiographic characteristics. The stent delivery failure rate, the use of guide-extension catheter or anchor balloon technique, and the procedural success rate were similar for both groups. Approximately two-thirds of lesions could be treated with one DES in the ultra-long DES group. At 1-year follow-up, the DOCO was similar for both groups (2.5% vs. 0.6%, p = .168). CONCLUSIONS: In daily clinical practice, ultra-long DES implantation is as safe and effective as multiple overlapping conventional DES implants in treating diffuse long CAD. However, ultra-long DES can reduce the number of stents. (Trial Registration: ClinicalTrials.gov Identifier: NCT02038127).

Validation of Biomarker-Based ABCD Score in Atrial Fibrillation Patients with a Non-Gender CHA2DS2-VASc Score 0-1: A Korean Multi-Center Cohort.

PURPOSE: Atrial fibrillation (AF) patients with low to intermediate risk, defined as non-gender CHA2DS2-VASc score of 0-1, are still at risk of stroke. This study verified the usefulness of ABCD score [age (≥60 years), B-type natriuretic peptide (BNP) or N-terminal pro-BNP (≥300 pg/mL), creatinine clearance (<50 mL/min/1.73 m²), and dimension of the left atrium (≥45 mm)] for stroke risk stratification in non-gender CHA2DS2-VASc score 0-1. MATERIALS AND METHODS: This multi-center cohort study retrospectively analyzed AF patients with non-gender CHA2DS2-VASc score 0-1. The primary endpoint was the incidence of stroke with or without antithrombotic therapy (ATT). An ABCD score was validated. RESULTS: Overall, 2694 patients [56.3±9.5 years; female, 726 (26.9%)] were followed-up for 4.0±2.8 years. The overall stroke rate was 0.84/100 person-years (P-Y), stratified as follows: 0.46/100 P-Y for an ABCD score of 0; 1.02/100 P-Y for an ABCD score ≥1. The ABCD score was superior to non-gender CHA2DS2-VASc score in the stroke risk stratification (C-index=0.618, p=0.015; net reclassification improvement=0.576, p=0.040; integrated differential improvement=0.033, p=0.066). ATT was prescribed in 2353 patients (86.5%), and the stroke rate was significantly lower in patients receiving non-vitamin K antagonist oral anticoagulant (NOAC) therapy and an ABCD score ≥1 than in those without ATT (0.44/100 P-Y vs. 1.55/100 P-Y; hazard ratio=0.26, 95% confidence interval 0.11-0.63, p=0.003). CONCLUSION: The biomarker-based ABCD score demonstrated improved stroke risk stratification in AF patients with non-gender CHA2DS2-VASc score 0-1. Furthermore, NOAC with an ABCD score ≥1 was associated with significantly lower stroke rate in AF patients with non-gender CHA2DS2-VASc score 0-1.

Reference diameter and characteristics of the distal radial artery based on ultrasonographic assessment.

BACKGROUND/AIMS: While distal radial artery (DRA) access is increasingly being used for diagnostic coronary angiography, limited information is available regarding DRA size. We aimed to determine the DRA reference diameters of Korean patients and identify the predictors of DRA diameter < 2.3 mm. METHODS: The outer bilateral DRA diameters were assessed using a linear ultrasound probe in 1,162 consecutive patients who underwent transthoracic echocardiography. The DRA diameter was measured by the perpendicular angle in the dorsum of the hand, and the average values were compared by sex. DRA diameter < 2.3 mm was defined as unsuitable for routine diagnostic coronary angiography using a 5 Fr introducer sheath. RESULTS: The mean DRA diameters were 2.31 ± 0.43 mm (right) and 2.35 ± 0.45 mm (left). The DRA was smaller in women than men (right: 2.15 ± 0.38 mm vs. 2.43 ± 0.44 mm, p < 0.001; left: 2.18 ± 0.39 mm vs. 2.47 ± 0.45 mm, p < 0.001). The DRA diameter was approximately 20% smaller than the radial artery diameter. A total of 630 (54.2%) and 574 (49.4%) patients had DRA diameter < 2.3 mm in the right and left hands, respectively. Female sex, low body mass index (BMI), and low body surface area (BSA) were significant predictors of DRA diameter < 2.3 mm. CONCLUSION: We provided reference DRA diameters for Korean patients. Approximately 50% of the studied patients had DRA diameter < 2.3 mm. Female sex, low BMI, and low BSA remained significant predictors of DRA diameter < 2.3 mm.

Evaluation of Adherence to Guideline for Heart Failure with Reduced Ejection Fraction in Heart Failure with Preserved Ejection Fraction and with or without Atrial Fibrillation.

BACKGROUND: This study evaluated the relationship between guideline adherence for heart failure (HF) with reduced ejection fraction (HFrEF) at discharge and relevant clinical outcomes in patients with acute HF with preserved ejection fraction (HFpEF) with or without atrial fibrillation (AF). METHODS: We analyzed Korean Acute Heart Failure Registry data for 707 patients with HFpEF with documented AF and 687 without AF. Guideline adherence was defined as good or poor according to the prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, ß-blockers, and mineralocorticoid receptor antagonists. Anticoagulation adherence was also incorporated for the AF group. RESULTS: Among patients with normal sinus rhythm, those with poor guideline adherence had a reduced prevalence of comorbidities and favorable clinical characteristics when compared with those with good guideline adherence. Using inverse probability of treatment weighting (IPTW) to address the bias of nonrandom treatment assignment, good adherence was associated with a poor 60-day composite endpoint in the multivariable Cox model (weighted hazard ratio [wHR], 1.74; 95% confidence interval [CI], 1.01-3.00; P = 0.045). For patients with AF, baseline clinical characteristics were similar according to the degree of adherence. The IPTW-adjusted analysis indicated that good adherence was significantly associated with the 60-day composite endpoint (wHR, 0.47; 95% CI, 0.27-0.79; P = 0.005). In the analysis excluding warfarin, good adherence was associated with 60-day re-hospitalization (wHR, 0.60; 95% CI, 0.37-0.98; P = 0.040), 1-year re-hospitalization (wHR, 0.67; 95% CI, 0.48-0.93; P = 0.018), and the composite endpoint (wHR, 0.77; 95% CI, 0.59-0.99; P = 0.041). CONCLUSION: Our findings indicate that good adherence to guidelines for HFrEF is associated with a better 60-day composite endpoint in patients with HFpEF with AF.

Beta-blocker Therapy at Discharge in Patients with Acute Heart Failure and Atrial Fibrillation.

BACKGROUND: ß-blockers (BBs) are considered primary therapy in stable heart failure (HF) with reduced ejection fraction (HFrEF) without atrial fibrillation (AF); evidence-based benefits of BB on outcome have been documented. However, BBs have not been shown to improve mortality or reduce hospital admissions in HF patients with AF. This study assessed the relationship between BBs at discharge and relevant clinical outcomes in acute heart failure (AHF) patients with AF. METHODS: From the Korean Acute Heart Failure Registry, 936 HFrEF and 639 HF patients with preserved ejection fraction (HFpEF) and AF were selected. Propensity score (PS) matching accounted for BB selection bias when assessing associations. RESULTS: BB-untreated patients in the overall cohort of HFrEF and HFpEF had greater deteriorated clinical and laboratory characteristics. In the 670 PS-matched cohort of HFrEF patients, incidences of all clinical events at 60 days and 1 year were not different according to use of BBs. In the 470 PS-matched cohort of HFpEF, rehospitalization and composite outcome at 6 months and 1 year more frequently occurred in non-users of BBs. After adjusting for covariates in the multivariable Cox model of matched cohorts, BB was not associated with clinical outcomes at 60 days and 1 year in HFrEF with AF patients. In HFpEF patients with AF, BB use was associated with reduced 6-month (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20-0.74) and 1-year rehospitalization (HR, 0.53; 95% CI, 0.34-0.82). CONCLUSION: In the HFrEF with AF PS-matched cohort, the use of BBs at discharge was not associated with clinical outcome. However, in HFpEF with AF, the use of BB was associated with reduced rehospitalization during the 6-month and 1-year follow up.

Transient receptor potential channel TRPV4 mediates TGF-ß1-induced differentiation of human ventricular fibroblasts.

BACKGROUND: Cardiac fibroblasts (CFs) are principal extracellular matrix-producing cells. In response to injury, CFs transdifferentiate into myofibroblasts. Intracellular calcium (Ca2+) signaling, involved in fibroblast proliferation and differentiation, is activated in fibroblasts through transient receptor potential (TRP) channels, but the function of these channels has not been investigated in human ventricular CFs. Under evaluation in this study, was the role of TRP channels in the differentiation of human ventricular CFs induced by transforming the growth factor beta (TGF-ß), a pro-fibrotic cytokine. METHODS: Human ventricular CFs were used in this study. The differentiation of CFs into myofibroblast was induced with TGF-ß and was identified by the expression of smooth muscle actin. RESULTS: Results indicate that Ca2+ signaling was an essential component of ventricular CF dif-ferentiation. CFs treated with TGF-ß demonstrated increased expression of a TRP channel, TRPV4, both at the mRNA and protein levels, which corresponded with CF-myofibroblast trans-differentiation, as evidenced by the upregulation of α-smooth muscle actin, a myofibroblast marker, and plasminogen activator inhibitor-1, which are fibrogenesis markers. An agonist of TRPV4 induced the conversion of CFs into myofibroblasts, whereas it's antagonist as well a Ca2+ chelating agent reduced it, indicating that the Ca2+ influx throughTRPV4 is required for CF trans-differentiation. Overall, these results dem-onstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway. CONCLUSIONS: Overall, these results demonstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway.

Comparison of Blood Pressure Variability Between Losartan and Amlodipine in Essential Hypertension (COMPAS-BPV).

BACKGROUND: Antihypertensive therapy using renin-angiotensin system blockers and calcium channel blockers to target blood pressure variability (BPV) has not yet been established. We aimed to compare the ability of losartan and amlodipine to lower BPV and systolic blood pressure (SBP) in essential hypertensive patients. METHODS: Patients were randomly assigned either losartan 50 mg or amlodipine 5 mg. Medications were uptitrated and hydrochlorothiazide was added according to protocol for 6 months. The primary endpoint was the office visit-to-visit SD of SBP. The secondary endpoints included average real variability (ARV), office SBP, and home SBP. RESULTS: The losartan group (n = 71) and amlodipine group (n = 73) finished the scheduled visits between April 2013 and May 2017. The office visit-to-visit SD of SBP was comparable between the losartan and amlodipine groups (11.0 ± 4.2 vs. 10.5 ± 3.8, P = 0.468). The office visit-to-visit ARV of SBP was significantly elevated in the losartan group (10.6 ± 4.3 vs. 9.1 ± 3.4, P = 0.02). The absolute SBP decrement from baseline to 6 months was similar between groups, although the office mean SBP at 6 months was higher in the losartan group (132.3 ± 12.9 vs. 127.5 ± 9.0 mm Hg, P = 0.011). In home blood pressure analysis, evening day-to-day BPV indexes (SD and ARV) were significantly higher in the losartan group at 6 months. CONCLUSIONS: The lowering effect of the office visit-to-visit SD of SBP was similar between losartan and amlodipine. However, the losartan group showed a higher office visit-to-visit ARV of SBP and evening day-to-day home BPV indexes. Therefore, amlodipine may be better to lower BPV in essential hypertensive patients.

Clinical Impact of Atypical Chest Pain and Diabetes Mellitus in Patients with Acute Myocardial Infarction from Prospective KAMIR-NIH Registry.

Atypical chest pain and diabetic autonomic neuropathy attract less clinical attention, leading to underdiagnosis and delayed treatment. To evaluate the long-term clinical impact of atypical chest pain and diabetes mellitus (DM), we categorized 11,159 patients with acute myocardial infarction (AMI) from the Korea AMI-National Institutes of Health between November 2011 and December 2015 into four groups (atypical DM, atypical non-DM, typical DM, and typical non-DM). The primary endpoint was defined as patient-oriented composite endpoint (POCE) at 2 years including all-cause death, any myocardial infarction (MI), and any revascularization. Patients with atypical chest pain showed higher 2-year mortality than those with typical chest pain in both DM (29.5% vs. 11.4%, p < 0.0001) and non-DM (20.4% vs. 6.3%, p < 0.0001) groups. The atypical DM group had the highest risks of POCE (hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.48-2.10), all-cause death (HR 2.23, 95% CI 1.80-2.76) and any MI (HR 2.34, 95% CI 1.51-3.64) in the adjusted model. In conclusion, atypical chest pain was significantly associated with mortality in patients with AMI. Among four groups, the atypical DM group showed the worst clinical outcomes at 2 years. Application of rapid rule in/out AMI protocols would be beneficial to improve clinical outcomes.

Guideline-directed therapy at discharge in patients with heart failure and atrial fibrillation.

OBJECTIVES: This study evaluated the relationship between guideline adherence for recommended therapy on discharge and relevant 60-day and 1-year clinical outcomes in patients with acute heart failure (HF) with reduced ejection fraction and atrial fibrillation (AF). METHODS: Of 5625 acute patients with HF in the Korean Acute Heart Failure registry, 986 patients with HF and documented AF were analysed. Guideline adherence scores were calculated for the prescription of ACE inhibitors, angiotensin receptor blockers, ß-blockers, mineralocorticoid receptor antagonists and anticoagulants. RESULTS: In patients with HF with AF, there was a significant trend of reduced 60-day and 1-year mortality rates and the composite end point with guideline adherence. According to the Cox proportion hazard model, poor adherence was associated with a significantly higher risk of 60-day mortality (HR 4.75; 95% CI 1.77 to 12.74) and the composite end point (HR 2.36; 95% CI 1.33 to 4.18) compared with good adherence. Furthermore, poor adherence was associated with a significantly higher risk of 1-year mortality compared with moderate (HR 1.64; 95% CI 1.15 to 2.33) and good adherence (HR 2.34; 95% CI 1.39 to 3.97) and with a higher risk of the 1-year composite end point compared with good adherence (HR 1.58; 95% CI 1.07 to 2.33). CONCLUSION: Better adherence to guidelines was associated with better 60-day and 1-year prognoses in patients with HF with AF.

Validation of post-stenting fractional flow reserve with intravascular ultrasound parameters for optimal stent deployment.

We aimed to evaluate the relationship between post-stent fractional flow reserve (FFR) and intravascular ultrasound (IVUS) parameters for stent optimization. IVUS and FFR measurements were performed in 101 coronary lesions after successful percutaneous coronary intervention (PCI). Quantitative IVUS parameters for stent optimization such as minimal intra-stent cross sectional area (CSA), proximal, and distal reference lumen CSA, and plaque burden (PB) at both edges of the stent related to the post-stent FFR. Mean post-stent FFR was 0.91 ± 0.06. Post-stent FFR ≤ 0.90 was observed in 46 (45.5%) lesions. The 55 lesions with post-stent FFR > 0.9 had larger proximal CSA (9.2 ± 2.9 mm2 vs. 7.4 ± 2.3 mm2, p = 0.001), distal reference lumen CSA (7.4 ± 2.7 mm2 vs. 6.3 ± 2.1 mm2, p = 0.017), minimum intra-stent lumen CSA (7.4 ± 2.5 mm2 vs. 6.1 ± 1.7 mm2, p = 0.004), and lower proximal reference PB (45 ± 8.2% vs. 50 ± 11%, p = 0.017) than did those with post-stent FFR ≤ 0.90. Post-stent FFR had an inverse correlation with age, left anterior descending artery (LAD) against non-LAD, and proximal reference PB and a positive correlation with pre-stent FFR, proximal and distal reference lumen CSA, and minimum intra-stent lumen CSA. Meanwhile, no correlation was found between post-stent FFR and stent length. Pre-stent FFR (ß = 0.544), proximal reference lumen CSA (ß = 0.530) and age (ß = - 0.251) were found to be independently associated with the post-stent FFR. Post-procedural FFR might partly reflect the appropriateness of PCI results in terms of the adequate expansion of the stent and full lesion coverage on IVUS.

Status of international normalized ratio control and treatment patterns in patients with nonvalvular atrial fibrillation taking vitamin K antagonist with or without antiplatelet therapy: Results from KORAFII registry.

BACKGROUND: Studies have shown that the concomitant use of a vitamin K antagonist (VKA) and an antiplatelet (APL) drug increased the bleeding risk and was less effective at preventing ischemic events. This study aimed to investigate the control status of international normalized ratio (INR) and the discontinuation rate of a VKA in patients taking VKA plus an APL drug compared with those taking a VKA alone. METHODS: Data were extracted from the KORean Atrial Fibrillation Investigation II registry, a multicenter noninterventional prospective observational study. Nonvalvular atrial fibrillation (NVAF) patients with CHADS 2 scores ≥ 1 who newly started (within 3 months) a VKA were enrolled and followed up for 1 year. RESULTS: A total of 866 NVAF patients (mean age, 67.7 years; 60.3% men) without a bleeding history were divided into the VKA+APL (n = 229) and VKA alone (n = 637) groups. During follow-up, mean INR level was lower in the VKA+APL group than in the VKA alone group (1.7 ± 0.8 vs 1.9 ± 0.9, P = 0.0005). INR levels were poorly controlled in both groups (66.1% and 64.7%, respectively). Patients in the VKA+APL group more frequently discontinued VKA than patients in the VKA alone group (28.8% vs 24.2%, P = 0.045). Major causes of VKA discontinuation were uncontrolled INR level and patient dissatisfaction or concerns. CONCLUSIONS: The conditions of NVAF patients were inadequately controlled with VKA with or without an APL. These findings suggest that other antithrombotic treatment options are warranted in NVAF patients to achieve INR control.

Prognostic Effect of Guideline-Directed Therapy Is More Noticeable Early in the Course of Heart Failure.

BACKGROUND: There have been few studies to evaluate the prognostic implications of guideline-directed therapy according to the temporal course of heart failure. This study assessed the relationship between adherence to guideline-directed therapy at discharge and 60-day clinical outcomes in de novo acute heart failure (AHF) and acute decompensated chronic heart failure (ADCHF) separately. METHODS: Among 5,625 AHF patients who were recruited from a multicenter cohort registry of Korean Acute Heart Failure, 2,769 patients with reduced ejection fraction were analyzed. Guideline-directed therapies were defined as the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), ß-blocker, and mineralocorticoid receptor antagonist. RESULTS: In de novo AHF, ACEI or ARB reduced re-hospitalization (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.34-0.95), mortality (HR, 0.41; 95% CI, 0.24-0.69) and composite endpoint (HR, 0.52; 95% CI, 0.36-0.77) rates. Beta-blockers reduced re-hospitalization (HR, 0.62; 95% CI, 0.41-0.95) and composite endpoint (HR, 0.65; 95% CI, 0.47-0.90) rates. In ADCHF, adherence to ACEI or ARB was associated with only mortality and ß-blockers with composite endpoint. CONCLUSION: The prognostic implications of adherence to guideline-directed therapy at discharge were more pronounced in de novo heart failure. We recommend that guideline-directed therapy be started as early as possible in the course of heart failure with reduced ejection fraction.

Co-treatment with interferon-γ and 1-methyl tryptophan ameliorates cardiac fibrosis through cardiac myofibroblasts apoptosis.

Cardiac remodeling characterized by cardiac fibrosis is a pathologic process occurring after acute myocardial infarction. Fibrosis can be ameliorated by interferon-gamma (IFN-γ), which is a soluble cytokine showing various effects such as anti-fibrosis, apoptosis, anti-proliferation, immunomodulation, and anti-viral activities. However, the role of IFN-γ in cardiac myofibroblasts is not well established. Therefore, we investigated the anti-fibrotic effects of IFN-γ in human cardiac myofibroblasts (hCMs) in vitro and whether indoleamine 2,3-dioxygenase (IDO), induced by IFN-γ and resulting in cell cycle arrest, plays an important role in regulating the biological activity of hCMs. After IFN-γ treatment, cell signaling pathways and DNA contents were analyzed to assess the biological activity of IFN-γ in hCMs. In addition, an IDO inhibitor (1-methyl tryptophan; 1-MT) was used to assess whether IDO plays a key role in regulating hCMs. IFN-γ significantly inhibited hCM proliferation, and IFN-γ-induced IDO expression caused cell cycle arrest in G0/G1 through tryptophan depletion. Moreover, IFN-γ treatment gradually suppressed the expression of α-smooth muscle actin. When IDO activity was inhibited by 1-MT, marked apoptosis was observed in hCMs through the induction of interferon regulatory factor, Fas, and Fas ligand. Our results suggest that IFN-γ plays key roles in anti-proliferative and anti-fibrotic activities in hCMs and further induces apoptosis via IDO inhibition. In conclusion, co-treatment with IFN-γ and 1-MT can ameliorate fibrosis in cardiac myofibroblasts through apoptosis.

Prognostic value of short-term follow-up B-type natriuretic peptide levels after hospital discharge in patients with acute myocardial infarction.

BACKGROUND: Elevated B-type natriuretic peptide (BNP) levels in patients hospitalized for acute myocardial infarction (AMI) are associated with heart failure and mortality. However, the role of BNP after hospital discharge is not clear. Therefore, we assessed the relationship between short-term follow-up BNP levels and clinical outcomes including all-cause mortality and major adverse cardiovascular events (MACE) in patients with AMI after hospital discharge. METHODS: From a prospective single-center percutaneous coronary intervention (PCI) registry, a total of 442 out of 2157 patients with AMI who had measurements for both initial and follow-up BNP levels within 2 months after discharge were retrospectively enrolled. Patients were divided into 4 groups (low-low, high-low, low-high, and high-high) according to their follow-up log-transformed BNP median values. RESULTS: The median follow-up period was 441 days (interquartile range [IQR], 362-861 days). Logistic regression analysis demonstrated that short-term follow-up BNP level was a significant predictor for all-cause mortality (odds ratio [OR], 2.265; 95% confidence interval [CI], 1.455-3.527) and MACE (OR, 1.43; 95% CI, 1.101-1.858) after adjustments for covariates. The initial BNP level did not predict both all-cause mortality and MACE. The group with high initial and high follow-up BNP levels was significantly associated with all-cause mortality (OR, 3.465; 95% CI, 1.122-10.700). CONCLUSIONS: Short-term follow-up BNP level after hospital discharge was a powerful prognostic marker for all-cause mortality and MACE in patients with AMI. The combination of short-term follow-up BNP level with initial BNP level was a better predictor of all-cause mortality.

Quality of Anticoagulation and Treatment Satisfaction in Patients with Non-Valvular Atrial Fibrillation Treated with Vitamin K Antagonist: Result from the KORean Atrial Fibrillation Investigation II.

BACKGROUND: Vitamin K antagonist (VKA) to prevent thromboembolism in non-valvular atrial fibrillation (NVAF) patients has limitations such as drug interaction. This study investigated the clinical characteristics of Korean patients treated with VKA for stroke prevention and assessed quality of VKA therapy and treatment satisfaction. METHODS: We conducted a multicenter, prospective, non-interventional study. Patients with CHADS2 ≥ 1 and treated with VKA (started within the last 3 months) were enrolled from April 2013 to March 2014. Demographic and clinical features including risk factors of stroke and VKA treatment information was collected at baseline. Treatment patterns and international normalized ratio (INR) level were evaluated during follow-up. Time in therapeutic range (TTR) > 60% indicated well-controlled INR. Treatment satisfaction on the VKA use was measured by Treatment Satisfaction Questionnaire for Medication (TSQM) after 3 months of follow-up. RESULTS: A total of 877 patients (age, 67; male, 60%) were enrolled and followed up for one year. More than half of patients (56%) had CHADS2 ≥ 2 and 83.6% had CHA2DS2-VASc ≥ 2. A total of 852 patients had one or more INR measurement during their follow-up period. Among those patients, 25.5% discontinued VKA treatment during follow-up. Of all patients, 626 patients (73%) had poor-controlled INR (TTR < 60%) measure. Patients' treatment satisfaction measured with TSQM was 55.6 in global satisfaction domain. CONCLUSION: INR was poorly controlled in Korean NVAF patients treated with VKA. VKA users also showed low treatment satisfaction.

Validation of the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) heart failure risk score and the effect of adding natriuretic peptide for predicting mortality after discharge in hospitalized patients with heart failure.

BACKGROUND: In clinical practice, a risk prediction model is an effective solitary program to predict prognosis in particular patient groups. B-type natriuretic peptide (BNP)and N-terminal pro-b-type natriuretic peptide (NT-proBNP) are widely recognized outcome-predicting factors for patients with heart failure (HF).This study derived external validation of a risk score to predict 1-year mortality after discharge in hospitalized patients with HF using the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC)program data. We also assessed the effect of adding BNP or NT-proBNP to this risk score model in a Korean HF registry population. METHOD AND RESULTS: We included 5625 patients from the Korean acute heart failure registry (KorAHF) and excluded those who died in hospital. The MAGGIC constructed a risk score to predict mortality in patients with HF by using 13 routinely available patient characteristics (age, gender, diabetes, chronic obstructive pulmonary disorder (COPD), HF diagnosed within the last 18 months, current smoker, NYHA class, use of beta blocker, ACEI or ARB, body mass index, systolic blood pressure, creatinine, and EF). We added BNP or NT-proBNP, which are the most important biomarkers, to the MAGGIC risk scoring system in patients with HF. The outcome measure was 1-year mortality. In multivariable analysis, BNP or NT-proBNP independently predicted death. The risk score was significantly varied between alive and dead groups (30.61 ± 6.32 vs. 24.80 ± 6.81, p < 0.001). After the conjoint use of BNP or NT-proBNP and MAGGIC risk score in patients with HF, a significant difference in risk score was noted (31.23 ± 6.46 vs. 25.25 ± 6.96, p < 0.001).The discrimination abilities of the risk score model with and without biomarker showed minimal improvement (C index of 0.734 for MAGGIC risk score and 0.736 for MAGGIC risk score plus BNP or NT-proBNP, p = 0.0502) and the calibration was found good. However, we achieved a significant improvement in net reclassification and integrated discrimination for mortality (NRI of 33.4%,p < 0.0001 and IDI of 0.002, p < 0.0001). CONCLUSION: In the KorAHF, the MAGGIC project HF risk score performed well in a large nationwide contemporary external validation cohort. Furthermore, the addition of BNP or NT-proBNPto the MAGGIC risk score was beneficial in predicting more death in hospitalized patients with HF.

Is There a Sex-Related Difference in the Obesity Paradox in Systolic Heart Failure? Sex-Related Difference in the Obesity Paradox.

PURPOSE: Obesity is often associated with better clinical outcomes in heart failure (HF). This so-called obesity paradox remains controversial. The aim of present study was to investigate the prognostic value of obesity in patients hospitalized for systolic HF. MATERIALS AND METHODS: We performed a pooled analysis of data from two multicenter, observational HF studies. Patients hospitalized for systolic HF were eligible for the present study. We divided the subjects into two groups, a normal body mass index (BMI) group and a high BMI group. Study endpoints included all-cause mortality and any re-hospitalization within 1 year. RESULTS: We enrolled 3145 patients (male, 1824; female, 1321). The high BMI group was significantly associated with lower 1-year mortality rate [odds ratio (OR), 0.543; 95% confidence interval (CI), 0.355-0.832] after adjusting for age, hypertension, diabetes, ischemic HF, previous myocardial infarction, serum creatinine level, anemia, and ejection fraction in men. After adjustment for clinical characteristics, high BMI was not significantly associated with 1-year mortality (OR, 0.739; 95% CI, 0.450-1.216) or 1-year re-hospitalization (OR, 0.958; 95% CI, 0.696-1.319) in women. CONCLUSION: In pooled analysis of data from two Korean HF registries, the high BMI group was independently associated with lower 1-year mortality rate from systolic HF, especially in men.

Remote Ischemic Conditioning by Effluent Collected from a Novel Isolated Hindlimb Model Reduces Infarct Size in an Isolated Heart Model.

BACKGROUND AND OBJECTIVES: Experimental protocols for remote ischemic conditioning (RIC) utilize models in which a tourniquet is placed around the hindlimb or effluent is collected from an isolated heart. In analyzing the humoral factors that act as signal transducers in these models, sampled blood can be influenced by systemic responses, while the effluent from an isolated heart might differ from that of the hindlimb. Thus, we designed a new isolated hindlimb model for RIC and tested whether the effluent from this model could affect ischemia/reperfusion (IR) injury and if the reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways are involved in RIC. MATERIALS AND METHODS: After positioning needles into the right iliac artery and vein of rats, Krebs-Henseleit buffer was perfused using a Langendorff apparatus, and effluent was collected. The RIC protocol consisted of 3 cycles of IR for 5 minutes. In the RIC effluent group, collected effluent was perfused in an isolated heart for 10 minutes before initiating IR injury. RESULTS: Compared with the control group, the infarct area in the RIC effluent group was significantly smaller (31.2%±3.8% vs. 20.6%±1.8%, p<0.050), while phosphorylation of signal transducer and activation of transcription-3 (STAT-3) was significantly increased. However, there was a trend of increased phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in this group. CONCLUSION: This is the first study to investigate the effect of effluent from a new isolated hindlimb model after RIC on IR injury in an isolated heart model. The RIC effluent was effective in reducing the IR injury, and the cardioprotective effect was associated with activation of the SAFE pathway.