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Abstract Statin is crucial for acute myocardial infarction (AMI) patients. However, the risk of new-onset diabetes mellitus (NODM) associated with statin is a concern. This study aimed to determine the incremental diabetogenic effects of statins according to their intensity and dose in AMI patients undergoing percutaneous coronary intervention (PCI). Among 13,104 patients enrolled in the Korea AMI Registry between 2011 and 2015, 6152 patients without diabetes mellitus (DM) who underwent PCI and received moderate-to-high-intensity atorvastatin and rosuvastatin were selected for the study. The endpoints were NODM and major adverse cardiovascular events (MACE), composite of all-cause mortality, recurrent MI, and revascularization up to 3 years. Among the participants, 3747 and 2405 received moderate- and high-intensity statins, respectively. The Kaplan–Meier curves demonstrated a higher incidence of NODM in patients with high-intensity statins than those with moderate-intensity. High-intensity statin was a significant predictor of NODM after adjusting for other co-variables (HR = 1.316, 95% CI 1.024–1.692; P

Introduction There is a lack of evidence to support the effectiveness of prolonged β-blocker therapy after stabilisation of patients with acute myocardial infarction (AMI) without heart failure (HF) or left ventricular systolic dysfunction.Methods and analysis The SMart Angioplasty Research Team: DEcision on Medical Therapy in Patients with Coronary Artery DIsease or Structural Heart Disease Undergoing InterventiON (SMART-DECISION) trial is a multicentre, prospective, open-label, randomised, non-inferiority trial designed to determine whether discontinuing β-blocker therapy after ≥1 year of maintenance in stabilised patients after AMI is non-inferior to continuing it. Patients eligible for participation are those without HF or left ventricular systolic dysfunction (ejection fraction >40%) who have been continuing β-blocker therapy for ≥1 year after AMI. A total of 2540 patients will be randomised 1:1 to continuation of β-blocker therapy or not. Randomisation will be stratified according to the type of AMI (ie, ST-segment-elevation MI or non-ST-segment-elevation MI), type of β-blocker (carvedilol, bisoprolol, nebivolol or other) and participating centre. The primary study endpoint is a composite of all-cause death, MI and hospitalisation for HF over a median follow-up period of 3.5 years (minimum, 2.5 years; maximum, 4.5 years). Adverse effects related to β-blocker therapy, the occurrence of atrial fibrillation, medical costs and Patient-reported Outcomes Measurement Information system-29 questionnaire responses will also be collected as secondary endpoints.Ethics and dissemination Ethics approval for this study was granted by the Institutional Review Board of Samsung Medical Center (no. 2020-10-176). Informed consent is obtained from every participant before randomisation. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences.Trial registration number ClinicalTrials.gov, NCT04769362.

Abstract Aims The clinical application of doxorubicin (DOX), a potent anthracycline anticancer drug that effectively treats various malignancies, is limited by its side effects, such as cardiomyopathy. Apurinic/apyrimidinic endonuclease 1/redox factor‐1 (APE1/Ref‐1) is a multifunctional protein that can be secreted and is a promising target for the reduction of DOX‐induced inflammation and oxidative stress. We aimed to investigate the protective role of secretory APE1/Ref‐1 against DOX‐induced cardiac injury. Methods and results Designated adenoviral preprotrypsin‐leading sequence APE1/Ref‐1 (Ad‐PPTLS‐APE1/Ref‐1) was used to overexpress secretory APE1/Ref‐1 and assess its role in preventing DOX‐induced cardiomyopathy in vitro. Our findings revealed that exposure to secretory APE1/Ref‐1 significantly decreased N‐terminal pro‐B‐type natriuretic peptide levels in DOX‐treated H9C2 cells. In addition, secretory APE1/Ref‐1 reduced the severity of cardiomyocyte injury and apoptosis in both in vitro and in vivo DOX‐induced cardiotoxicity models. The observed cardioprotective effects of secretory APE1/Ref‐1 were mediated via inhibition of the p53 signalling pathway and enhancement of cell viability through attenuation of oxidative stress in DOX‐treated cardiomyocytes. Conclusions Our study provides evidence that secretory APE1/Ref‐1 has the potential to inhibit DOX‐induced cardiac toxicity by inhibiting oxidative stress and p53 related apoptosis both in vitro and in vivo. These findings suggest that secretory APE1/Ref‐1 supplementation is a promising strategy to attenuate DOX‐induced cardiomyocyte damage in a preclinical model. Further clinical investigations are essential to validate the therapeutic efficacy and safety of the intervention in human subjects.

Abstract The clinical impact of different polymer technologies in newer-generation drug-eluting stents (DESs) for patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains poorly understood. We investigated the efficacy and safety of durable polymer DESs (DP-DESs) compared with biodegradable polymer DESs (BP-DESs). A total of 620 patients who underwent percutaneous coronary intervention with newer-generation DESs for AMI complicated by CS was divided into two groups based on polymer technology: the DP-DES group (n = 374) and the BP-DES group (n = 246). The primary outcome was target vessel failure (TVF) during a 12-month follow-up, defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization. Both the DP-DES and BP-DES groups exhibited low stent thrombosis rates (1.3% vs. 1.6%, p = 0.660). The risk of TVF did not significantly differ between the two groups (34.2% vs. 28.5%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.69–1.29, p = 0.721). This finding remained consistent after adjustment with inverse probability of treatment weighting (28.1% vs. 25.1%, HR 0.98, 95% CI 0.77–1.27, p = 0.899). In AMI patients complicated by CS, the risk of a composite of cardiac death, myocardial infarction, or target vessel revascularization was not significantly different between those treated with DP-DESs and those treated with BP-DESs. Trial registration: RESCUE registry, https://clinicaltrials.gov/ct2/show/NCT02985008 , NCT02985008.

Abstract Early identification of women at high risk for cardiovascular diseases (CVD), with subsequent monitoring, will allow for improved clinical outcomes and generally better quality of life. This study aimed to identify the associations between early menopause, abnormal diastolic function, and clinical outcomes. This retrospective study included 795 menopausal women from is a nationwide, multicenter, registry of patients with suspected angina visiting outpatient clinic. The patients into two groups: early and normal menopause (menopausal age ≤ 45 and > 45 years, respectively). If participants met > 50% of the diastolic function criteria, they were classified as having normal diastolic function. Multivariable-adjusted Cox models were used to test associations between menopausal age and clinical outcomes including the incidence of major adverse cardiovascular events (MACE), over a median follow-up period of 771 days. Early menopause was associated with increased waist circumference (p = 0.001), diabetes prevalence (p = 0.003), obstructive coronary artery disease (p = 0.005), abnormal diastolic function (p = 0.003) and greater incidences of MACE, acute coronary syndrome, and hospitalization for heart failure. In patients with abnormal diastolic function, early menopause increased MACE risk significantly, with no significant difference in normal diastolic function. These findings highlight early menopause and abnormal diastolic function as being potential risk markers in women for midlife CVD events.

Background: Little is known about the association between seasonal variation and prognosis in patients with CS caused by AMI. Objectives: We investigated the 12-month clinical outcomes in patients treated with percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) according to season. Methods: A total of 695 patients undergoing PCI for AMI complicated by CS was enrolled from 12 centers in South Korea. The study patients were divided into four groups according to season in which the AMI with CS occurred (spring, n = 178 vs. summer, n = 155 vs. autumn, n = 182 vs. winter, n = 180). We compared major adverse cardiovascular events (MACEs; the composite of cardiac death, myocardial infarction, re-hospitalization due to heart failure, and any revascularization) between the four groups. Results: The risk of MACE during the 12 months after CS was similar in the four groups: spring, 68 patients, vs. summer, 69, vs. autumn, 73, vs. winter, 68 (p = 0.587). Multivariate Cox-regression analysis revealed no significant difference in 12-month MACE among groups compared to the spring group after inverse probability of treatment weighting adjustment (summer, HR 1.40, 95 % CI 0.98–1.99, p = 0.062; autumn, HR 1.26, 95 % CI 0.89–1.80, p = 0.193; winter, HR 1.18, 95 % CI 0.83–1.67, p = 0.356). The similarity of MACE between the four groups was consistent across a variety of subgroups. Conclusions: After adjusting for baseline differences, seasonal variation seems not to influence the mid-term risk of 12-month MACE in patients treated with PCI for AMI complicated by CS. Condensed abstract: Data are limited regarding the association between seasonal variation and prognosis in patients with cardiogenic shock (CS) caused by AMI. This study divided patients undergoing PCI for AMI complicated by CS into four groups based on the season of occurrence and found no significant differences in 12-month MACE between the groups after adjusting for bias and confounding factors. Multivariate analysis revealed consistent MACE similarity across subgroups. The study suggests that seasonal variation has no impact on the mid-term risk of 12-month MACE in patients with CS caused by AMI, after adjusting for baseline differences. Trial registration: ClinicalTrials.gov NCT02985008RESCUE (REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy of left ventricular assist device for Korean patients with cardiogenic shock), NCT02985008, Registered December 5, 2016 - retrospectively and prospectively. Irb information: This study was approved by the institutional review board of Samsung Medical Center (Reference number: 2016-03-130).

Background Clinical outcome of ischemic cardiogenic shock (CS) requiring extracorporeal membrane oxygenation is highly variable, necessitating appropriate assessment of prognosis. However, a systemic predictive model estimating the mortality of refractory ischemic CS is lacking. The PRECISE (Prediction of In‐Hospital Mortality for Patients With Refractory Ischemic Cardiogenic Shock Requiring Veno‐Arterial Extracorporeal Membrane Oxygenation Support) score was developed to predict the prognosis of refractory ischemic CS due to acute myocardial infarction. Methods and Results Data were obtained from the multicenter CS registry RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock) that consists of 322 patients with acute myocardial infarction complicated by refractory ischemic CS requiring extracorporeal membrane oxygenation support. Fifteen parameters were selected to assess in‐hospital mortality. The developed model was validated internally and externally using an independent external cohort (n=138). Among 322 patients, 138 (42.9%) survived postdischarge. Fifteen predictors were included for model development: age, diastolic blood pressure, hypertension, chronic kidney disease, peak lactic acid, serum creatinine, lowest left ventricular ejection fraction, vasoactive inotropic score, shock to extracorporeal membrane oxygenation insertion time, extracorporeal cardiopulmonary resuscitation, use of intra‐aortic balloon pump, continuous renal replacement therapy, mechanical ventilator, successful coronary revascularization, and staged percutaneous coronary intervention. The PRECISE score yielded a high area under the receiver‐operating characteristic curve (0.894 [95% CI, 0.860–0.927]). External validation and calibration resulted in competent sensitivity (area under the receiver‐operating characteristic curve, 0.895 [95% CI, 0.853–0.930]). Conclusions The PRECISE score demonstrated high predictive performance and directly translates into the expected in‐hospital mortality rate. The PRECISE score may be used to support clinical decision‐making in ischemic CS (www.theprecisescore.com). Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.

Abstract Limited knowledge exists regarding the predictors of mortality after successful weaning of venoarterial extracorporeal membrane oxygenation (ECMO). We aimed to identify predictors of in-hospital mortality in patients with cardiogenic shock (CS) after successful weaning from ECMO. Data were obtained from a multicenter registry of CS. Successful ECMO weaning was defined as survival with minimal mean arterial pressure (> 65 mmHg) for > 24 h after ECMO removal. The primary outcome was in-hospital mortality after successful ECMO weaning. Among 1247 patients with CS, 485 received ECMO, and 262 were successfully weaned from ECMO. In-hospital mortality occurred in 48 patients (18.3%). Survivors at discharge differed significantly from non-survivors in age, cardiovascular comorbidities, cause of CS, left ventricular ejection fraction, and use of adjunctive therapy. Five independent predictors for in-hospital mortality were identified: use of continuous renal replacement therapy (odds ratio 5.429, 95% confidence interval [CI] 2.468–11.940; p

Abstract Background To assess the efficacy and safety of a combination therapy involving fimasartan, amlodipine, and rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond to fimasartan monotherapy. Methods This phase III, randomized, double-blind, multicenter study was conducted in adults aged 19–70 years. Patients who voluntarily consented were screened for eligibility to enroll in the study. Patients who failed to respond to 4 weeks of fimasartan monotherapy were randomized with a 1:1:1 ratio to the fimasartan 60 mg/amlodipine 10 mg + rosuvastatin 20 mg (FMS/ALD + RSV) as study group, fimasartan 60 mg/amlodipine 10 mg (FMS/ALD) as control 1 group, and fimasartan 60 mg + rosuvastatin 20 mg (FMS + RSV) as control 2 group. The primary efficacy endpoints were the change in the sitting systolic blood pressure and the rate of change in the low-density lipoprotein cholesterol (LDL-C) level from baseline to 8 weeks. The adverse events, adverse drug reactions, physical examination findings, laboratory test results, electrocardiograms, and vital signs were evaluated to assess safety in the study. Results Of 138 randomized patients, 131 were conducted efficacy analysis, and 125 completed the study. For the change in LDL-C and sitting SBP (SiSBP) as primary efficacy assessments, the change in LDL-C at week 8 was significantly reduce in the FMS/ALD + RSV group than in the control 1 group (P

Background Despite the benefit of culprit‐only percutaneous coronary intervention (PCI) in the CULPRIT‐SHOCK (Culprit Lesion Only PCI Versus Multi‐vessel PCI in Cardiogenic Shock) trial, the optimal revascularization strategy for refractory cardiogenic shock (CS) requiring mechanical circulatory support devices remains controversial. This study aimed to compare clinical outcomes between the culprit‐only and immediate multivessel PCI strategies in patients with acute myocardial infarction complicated by CS who underwent venoarterial‐extracorporeal membrane oxygenation before revascularization. Methods and Results This study included patient‐pooled data from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Devices for Korean Patients With Cardiogenic Shock) and SMC‐ECMO (Samsung Medical Center–Extracorporeal Membrane Oxygenation) registries. A total of 315 patients with acute myocardial infarction with multivessel disease who underwent venoarterial‐extracorporeal membrane oxygenation before revascularization attributable to refractory CS were included in this analysis. The study population was classified into culprit‐only versus immediate multivessel PCI according to nonculprit lesion treatment strategies. The primary end point was 30‐day mortality or renal‐replacement therapy, and the key secondary end point was 12‐month follow‐up mortality. Among the study population, 175 (55.6%) underwent culprit‐only PCI and 140 (44.4%) underwent immediate multivessel PCI. Compared with culprit‐only PCI, immediate multivessel PCI was associated with significantly lower risks of 30‐day mortality or renal‐replacement therapy (68.0% versus 54.3%; P=0.018) and all‐cause mortality during 12 months of follow‐up (59.5% versus 47.5%; hazard ratio [HR], 0.689 [95% CI, 0.506–0.939]; P=0.018) in patients with acute myocardial infarction and CS who underwent venoarterial‐extracorporeal membrane oxygenation before revascularization. These results were also consistent in the 99 pairs of propensity score–matched population (60.6% versus 43.6%; HR, 0.622 [95% CI, 0.420–0.922]; P=0.018). Conclusions Among patients with acute myocardial infarction with multivessel disease complicated by advanced CS requiring venoarterial‐extracorporeal membrane oxygenation before revascularization, immediate multivessel PCI was associated with lower incidences of 30‐day mortality or renal replacement therapy and 12‐month follow‐up mortality, compared with culprit‐only PCI. Registration Information clinicaltrials.gov. Identifier: NCT02985008.

Background: Early risk stratification is necessary for optimal determination of the treatment strategy in cardiogenic shock (CS) complicating acute coronary syndrome (ACS). Therefore, we evaluated the prognostic impact of an intra-aortic balloon pump on the cardiogenic shock (IABP-SHOCK) II score according to the treatment strategies in ACS complicated by CS using the RESCUE (REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy of left ventricular assist device for Korean patients with cardiogenic shock) registry. Methods: The RESCUE registry contains multicenter observational retrospective and prospective cohorts that include 1247 patients with CS from 12 centers in Korea. A total of 865 patients with ACS complicated by CS were selected and stratified into low-, intermediate- and high-risk categories according to their IABP-SHOCK II scores and then according to treatment: non-mechanical support, IABP, and extracorporeal membrane oxygenators (ECMOs). The primary outcome was all-cause mortality during follow-up. Results: The observed mortality rates for the low-, intermediate-, and high-IABP-SHOCK II score risk categories were 28.8%, 52.4%, and 69.8%, respectively (p < 0.01). Patients in the non-mechanical support and IABP groups showed an increasingly elevated risk of all-cause mortality as their risk scores increased from low to high. In the ECMO group, the risk of all-cause mortality did not differ between the intermediate- and high-risk categories (HR = 1.21, 95% CI: 0.81–1.81, p = 0.33). The IABP-SHOCK II scores for the non-mechanical support and IABP groups showed a better predictive performance (area under curve [AUC] = 0.70, 95% CI: 0.65–0.76) for mortality compared with the EMCO group (AUC = 0.61, 95% CI 0.54–0.67; p-value for comparison = 0.02). Conclusions: Risk stratification using the IABP-SHOCK II score is useful for predicting mortality in ACS complicated by CS when patients are treated with non-mechanical support or IABP. However, its prognostic value may be unsatisfactory in severe cases where patients require ECMOs.

ObjectivesWe evaluated the clinical impact of residual non-culprit left main coronary artery disease (LMCAD) on prognosis in patients undergoing emergent percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) complicated by cardiogenic shock (CS).MethodsA total of 429 patients who underwent PCI for AMI complicated by CS was enrolled from 12 centers in the Republic of Korea. The patients were divided into two groups according to presence of non-culprit LMCAD or not: the LMCAD non-culprit group (n = 43) and the no LMCAD group (n = 386). Primary outcome was major adverse cardiac event (MACE, defined as a composite of cardiac death, myocardial infarction, or repeat revascularization). Propensity score matching analysis was performed to reduce selection bias and potential confounding factors.ResultsDuring a 12-month follow-up, a total of 168 MACEs occurred (LMCAD non-culprit group, 17 [39.5%] vs. no LMCAD group, 151 [39.1%]). Multivariate analysis revealed no significant difference in the incidence of MACE at 12 months between the LMCAD non-culprit and no LMCAD groups (adjusted hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.58 to 1.62, p = 0.901). After propensity score matching, the incidence of MACE was still similar between the two groups (HR 0.64; 95% CI 0.33 to 1.23; p = 0.180). The similarity of MACEs between the two groups was consistent across a variety of subgroups.ConclusionsAfter adjusting for baseline differences, residual non-culprit LMCAD does not appear to increase the risk of MACEs at 12 months in patients undergoing emergent PCI for AMI complicated by CS.

BackgroundDiabetes mellitus (DM) is a critical risk factor for the pathogenesis and progression of coronary artery disease, with a higher prevalence of complex coronary artery disease, including bifurcation lesions. This study aimed to elucidate the optimal stenting strategy for coronary bifurcation lesions in patients with DM.MethodsA total of 905 patients with DM and bifurcation lesions treated with second-generation drug-eluting stents (DES) from a multicenter retrospective patient cohort were analyzed. The primary outcome was the 5-year incidence of target lesion failure (TLF), which was defined as a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization.ResultsAmong all patients with DM with significant bifurcation lesions, 729 (80.6%) and 176 (19.4%) were treated with one- and two-stent strategies, respectively. TLF incidence differed according to the stenting strategy during the mean follow-up of 42 ± 20 months. Among the stent strategies, T- and V-stents were associated with a higher TLF incidence than one-stent strategy (24.0 vs. 7.3%, p < 0.001), whereas no difference was observed in TLF between the one-stent strategy and crush or culotte technique (7.3 vs. 5.9%, p = 0.645). The T- or V-stent technique was an independent predictor of TLF in multivariate analysis (hazard ratio, 3.592; 95% confidence interval, 2.117–6.095; p < 0.001). Chronic kidney disease, reduced left ventricular ejection fraction, and left main bifurcation were independent predictors of TLF in patients with DM.ConclusionT- or V-stenting in patients with DM resulted in increased cardiovascular events after second-generation DES implantation.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03068494?term=03068494&draw=2&rank=1, identifier: NCT03068494.

Abstract Background Limited data are available on the clinical significance of lactate clearance (LC) in patients with cardiogenic shock (CS). This study investigated the prognostic role of LC in CS patients. Methods We analyzed data from 628 patients in the RESCUE registry, a multicenter, observational cohort enrolled between January 2014 and December 2018. Univariable logistic regression analysis was performed to determine the prognostic implications of 24 h LC, and then patients were divided into two groups according to the cut-off value of 24 h LC (high lactate clearance [HLC] group vs. low lactate clearance [LLC] group). The primary outcome was in-hospital mortality. We also assessed all-cause mortality at 12 month follow-up and compared the prognostic performance of 24 h LC according to initial serum lactate level. Results In the univariable logistic regression analysis, 24 h LC was associated with in-hospital mortality (odds ratio 0.989, 95% confidence interval [CI] 0.985–0.993, p 5 mmol/L than in those with serum lactate ≤ 5 mmol/L (c-statistics of initial serum lactate > 5 mmol/L = 0.782 vs. c-statistics of initial serum lactate ≤ 5 mmol/L = 0.660, p = 0.011). Conclusions Higher LC during the early phase of CS was associated with reduced risk of in-hospital and 12 month all-cause mortalities. Patients with LC ≥ 64% during the 24 h after CS onset could expect a favorable prognosis, especially those with an initial serum lactate > 5 mmol/L. Trial registration: RESCUE (REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy of left ventricular assist device for Korean patients with cardiogenic shock), NCT02985008, Registered December 5, 2016—retrospectively and prospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT02985008

Abstract Aims This study aimed to investigate differences in baseline and treatment characteristics, and in‐hospital mortality according to the aetiologies of cardiogenic shock in patients undergoing veno‐arterial‐extracorporeal membrane oxygenation (VA‐ECMO). Methods and results The RESCUE registry is a multicentre, observational cohort that includes 1247 patients with cardiogenic shock from 12 centres. A total of 496 patients requiring VA‐ECMO were finally selected, and the study population was stratified by cardiogenic shock aetiology [ischaemic cardiomyopathy (ICM, n = 342) and non‐ICM (NICM, n = 154)]. The primary outcome of interest was in‐hospital mortality. Sensitivity analyses including propensity‐score matching adjustments were performed. Mean age of the entire population was 61.8 ± 14.2, and 30.8% were women. There were significant differences in baseline characteristics; notable differences included the older age of patients with ICM (65.1 ± 13.7 vs. 58.2 ± 13.8, P

Background: The optimal side branch (SB) treatment strategy after simple crossover stenting in bifurcation lesions is still controversial. Objectives: The purpose of this study was to compare the long-term outcomes of a 1-stent strategy with simple crossover alone versus with an additional SB–opening procedure in patients with left main (LM) and non-LM coronary bifurcation lesions. Methods: Patients who underwent percutaneous coronary intervention with a 1-stent strategy for bifurcation lesions including LM were selected from the COBIS (Coronary Bifurcation Stenting) III registry and divided into the simple crossover–alone group and SB-opening group. Clinical outcomes were assessed by the 5-year rate of target lesion failure (a composite of cardiac death, target vessel myocardial infarction, and target lesion repeat revascularization). Results: Among 2,194 patients who underwent the 1-stent strategy, 1,685 (76.8%) patients were treated with simple crossover alone, and 509 (23.2%) patients were treated with an additional SB-opening procedure. Although the baseline SB angiographic disease was more severe in the SB-opening group, the final lumen diameter of the SB was larger. The 5-year observed target lesion failure rate was similar between the 2 groups (7.0% in the simple crossover vs. 6.7% in SB-opening group; hazard ratio: 0.99; 95% confidence interval: 0.66 to 1.48; p = 0.947), even in the subgroup analyses including LM (9.5% vs. 11.3%; p = 0.442) and true bifurcation (5.3% vs. 7.8%; p = 0.362). The results were not changed after an inverse probability of treatment weighting adjustment. There was no difference in the overall and SB-related target lesion revascularization rate in both groups. Conclusions: The long-term clinical outcome of the 1-stent strategy with simple crossover alone for coronary bifurcation lesions was acceptable compared to those of additional SB-opening procedures. (Korean Coronary Bifurcation Stenting [COBIS] Registry III [COBIS III]; NCT03068494)

Background: There is a paucity of data regarding the long-term clinical outcomes of first- versus second-generation drug-eluting stent (DES), especially when used to treat complex lesions such as bifurcation lesions. Objectives: The current study compares the efficacy and safety of first- versus second-generation DES at the 5-year follow-up in patients who underwent bifurcation percutaneous coronary intervention (PCI). Methods: A total of 5,498 patients with a bifurcation lesion who underwent PCI were pooled at a single patient level from COBIS (Coronary Bifurcation Stenting) registries II and III. Five-year target lesion failure (TLF) (the composite of cardiac death, myocardial infarction [MI], and target lesion revascularization [TLR]) and cardiac death or MI were compared between the use of first-generation DES (n = 2,436) and second-generation DES (n = 3,062) during PCI. Propensity score matching was performed to reduce selection bias. Results: After a 1:1 propensity score matching procedure was conducted, the cohort consisted of 1,702 matched pairs. Patients treated with second-generation DES had a significantly lower risk of TLF at 5 years than those treated with first-generation DES in both overall and propensity-matched populations (matched hazard ratio [HRmatched]: 0.576; 95% confidence interval [CI]: 0.456 to 0.727; p

Background Several studies have shown that obesity is associated with better outcomes in patients with cardiogenic shock (CS). Although this phenomenon, the “obesity paradox,” reportedly manifests differently based on sex in other disease entities, it has not yet been investigated in patients with CS. Methods and Results A total of 1227 patients with CS from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock) registry in Korea were analyzed. The study population was classified into obese and nonobese groups according to Asian Pacific criteria (BMI ≥25.0 kg/m2 for obese). The clinical impact of obesity on in‐hospital mortality according to sex was analyzed using logistic regression analysis and restricted cubic spline curves. The in‐hospital mortality rate was significantly lower in obese men than nonobese men (34.2% versus 24.1%, respectively; P=0.004), while the difference was not significant in women (37.3% versus 35.8%, respectively; P=0.884). As a continuous variable, higher BMI showed a protective effect in men; conversely, BMI was not associated with clinical outcomes in women. Compared with patients with normal weight, obesity was associated with a decreased risk of in‐hospital death in men (multivariable‐adjusted odds ratio [OR], 0.63; CI, 0.43–0.92 [P=0.016]), but not in women (multivariable‐adjusted OR, 0.94; 95% CI, 0.55–1.61 [P=0.828]). The interaction P value for the association between BMI and sex was 0.023. Conclusions The obesity paradox exists and apparently occurs in men among patients with CS. The differential effect of BMI on in‐hospital mortality was observed according to sex. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.

Background/Aims Chest pain in patients with obstructive coronary artery disease (OCAD) is affected by several social factors. The gender-based differences in chest pain among Koreans have yet to be investigated. Methods The study consecutively enrolled 1,549 patients (male/female, 514/1,035; 61 ± 11 years old) with suspected angina. The predictive factors for OCAD based on gender were evaluated. Results Men experienced more squeezing type pain on the left side of chest, while women demonstrated more dull quality pain in the retrosternal and epigastric area. After adjustment for risk factors, pain in the retrosternal area (odds ratio [OR], 1.491; 95% confidence interval [CI], 1.178 to 1.887) and aggravation by exercise (OR, 2.235; 95% CI, 1.745 to 2.861) were positively associated with OCAD. In men, shorter duration (OR, 1.581; 95% CI, 1.086 to 2.303) and dyspnea (OR, 1.610; 95% CI, 1.040 to 2.490) increased the probability for OCAD, while left-sided chest pain suggested a low probability for OCAD (OR, 0.590; 95% CI, 0.388 to 0.897). In women, aggravation by emotional stress (OR, 0.348; 95% CI, 0.162 to 0.746) and dizziness (OR, 0.457; 95% CI, 0.246 to 0.849) decreased the probability for OCAD. Conclusions This is the first study to focus on gender differences in chest pain among Koreans with angina. Symptoms with high probability for OCAD were different between sexes. Our findings suggest that patient’s medical history in pretest assessment for OCAD should be individualized considering gender.

Background Despite advances in devices and techniques, coronary bifurcation lesion remains a challenging lesion subset in the field of percutaneous coronary intervention (PCI). We evaluate 10‐year trends in bifurcation PCI and their effects on patient outcomes. Methods and Results We analyzed 10‐year trends in patient/lesion characteristics, devices, PCI strategy, stent optimization techniques, and clinical outcomes using data from 5498 patients who underwent bifurcation PCI from 2004 to 2015. Clinical outcomes 2 years after the index procedure were evaluated in terms of target vessel failure (a composite of cardiac death, myocardial infarction, and target vessel revascularization) and a patient‐oriented composite outcome (a composite of all‐cause death, myocardial infarction, and any revascularization). During the 10‐year study period, patient and lesion complexity, such as multivessel disease, diabetes mellitus, chronic kidney disease, and left main bifurcation, increased continuously (all P

Abstract Background Hypertension is an important risk factor for cardiovascular disease, even in the elderly. Fimasartan is a new non-peptide angiotensin II receptor blocker with a selective type I receptor blocking effect. The objective of this study is to confirm the safety and the non-inferiority of the blood pressure–lowering effect of fimasartan compared with those of perindopril, which has been proven safe and effective in elderly patients with hypertension. Methods This is a randomized, double-blind, active-controlled, two-parallel group, optional-titration, multicenter, phase 3 study comparing the efficacy and safety of fimasartan and perindopril arginine. The study population consists of individuals 70 years old or older with essential hypertension. The primary outcome will be a change in sitting systolic blood pressure from baseline after the administration of the investigational product for 8 weeks. The secondary outcomes will be a change in sitting diastolic blood pressure from baseline and changes in sitting systolic blood pressure and diastolic blood pressure from baseline after the administration of the investigational product for 4, 16, and 24 weeks. The sample size will be 119 subjects for each group to confer enough power to test for the primary outcome. Discussion Research to confirm the efficacy and safety of a new medicine compared with those of previously proven anti-hypertensive drugs is beneficial to guide physicians in the selection of therapeutic agents. If it is confirmed that the new drug is not inferior to the existing drug, the drug will be considered as an option in the treatment of hypertension in elderly patients. Trial registration ClinicalTrials.gov Identifier: NCT03246555, registered on July 25, 2017.

Background This study sought to investigate the safety of 3‐month dual antiplatelet therapy (DAPT) in patients receiving ultrathin sirolimus‐eluting stents with biodegradable polymer (Orsiro). Methods and Results The SMART‐CHOICE (Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Anti‐ platelet Therapy in Patients Undergoing Implantation of Coronary Drug‐Eluting Stents) randomized trial compared 3‐month DAPT followed by P2Y12 inhibitor monotherapy with 12‐month DAPT in 2993 patients undergoing percutaneous coronary intervention. The present analysis was a prespecified subgroup analysis for patients receiving Orsiro stents. As a post hoc analysis, comparisons between Orsiro and everolimus‐eluting stents were also done among patients receiving 3‐month DAPT. Of 972 patients receiving Orsiro stents, 481 patients were randomly assigned to 3‐month DAPT and 491 to 12‐month DAPT. At 12 months, the target vessel failure, defined as a composite of cardiac death, target vessel–related myocardial infarction, or target vessel revascularization, occurred in 8 patients (1.7%) in the 3‐month DAPT group and in 14 patients (2.9%) in the 12‐month DAPT group (hazard ratio [HR], 0.58; 95% CI, 0.24–1.39; P=0.22). In whole population who were randomly assigned to receive 3‐month DAPT (n=1495), there was no significant difference in the target vessel failure between the Orsiro group and the everolimus‐eluting stent group (n=1014) (1.7% versus 1.8%; HR, 0.96; 95% CI, 0.41–2.22; P=0.92). Conclusions In patients receiving Orsiro stents, clinical outcomes at 1 year were similar between the 3‐month DAPT followed by P2Y12 inhibitor monotherapy and 12‐month DAPT strategies. With 3‐month DAPT, there was no significant difference in target vessel failure between Orsiro and everolimus‐eluting stents. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02079194.

Immunoglobulin G4 (IgG4)-related periaortitis and periarteritis are rare systemic inflammatory and fibrosclerosing diseases, usually involving the aorta and its main branches. We report a pathologically confirmed case of IgG4-related periaortitis involving the thoracoabdominal aorta, which can be confused with intramural hematoma or periaortic lymphoma.

Background: Although brachial-ankle pulse wave velocity (baPWV) is well-known for predicting the cardiovascular mortality and morbidity, its anticipated value is not demonstrated well concerning acute stroke. Methods: Total 1557 patients with acute stroke who performed baPWV were enrolled. We evaluated the prognostic value of baPWV predicting all-cause death and vascular death in patients with acute stroke Results: Highest quartile of baPWV was ≥23.64 m/s. All-caused deaths (including vascular death; 71) were 109 patients during follow-up periods (median 905 days). Multivariate Cox regression analysis revealed that patients with the highest quartile of baPWV had higher risk for vascular death when they are compared with patients with all other three quartiles of baPWV (Hazard ratio with 95% confidence interval [CI] 1.879 [1.022–3.456], p = .042 for vascular death). Conclusion: High baPWV was a strong prognostic value of vascular death in patients with acute stroke

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is involved in DNA base repair and reducing activity. However, the role of APE1/Ref-1 in atherosclerosis is unclear. Herein, we investigated the role of APE1/Ref-1 in atherosclerotic apolipoprotein E (ApoE−/−) mice fed with a Western-type diet. We found that serologic APE1/Ref-1 was strongly correlated with vascular inflammation in these mice. Neutrophil/lymphocyte ratio (NLR), endothelial cell/macrophage activation, and atherosclerotic plaque formation, reflected by atherosclerotic inflammation, were increased in the ApoE−/− mice fed with a Western-type diet. APE1/Ref-1 expression was upregulated in aortic tissues of these mice, and was co-localized with cells positive for cluster of differentiation 31 (CD31) and galectin-3, suggesting endothelial cell/macrophage expression of APE1/Ref-1. Interestingly, APE1/Ref-1 plasma levels of ApoE−/− mice fed with a Western-type diet were significantly increased compared with those of the mice fed with normal diet (15.76 ± 3.19 ng/mL vs. 3.51 ± 0.50 ng/mL, p < 0.05), and were suppressed by atorvastatin administration. Correlation analysis showed high correlation between plasma APE1/Ref-1 levels and NLR, a marker of systemic inflammation. The cut-off value for APE1/Ref-1 for predicting atherosclerotic inflammation at 4.903 ng/mL showed sensitivity of 100% and specificity of 91%. We conclude that APE1/Ref-1 expression is upregulated in aortic endothelial cells/macrophages of atherosclerotic mice, and that plasma APE1/Ref-1 levels could predict atherosclerotic inflammation.

Cardiac lipoma is a rare neoplasm of encapsulated mature adult adipose tissue. It is usually asymptomatic, but it may be related to hemodynamic obstruction depending on its location. We report a typical case of right ventricular lipomatous mass and multifocal fat infiltration of both ventricles, which were detected incidentally in a young woman.

There are limited data about clinical outcomes of biodegradable polymer biolimus-eluting BioMatrix stents (BP-BES) and durable polymer everolimus-eluting Xience stents (DP-EES) in real world practice. We sought to compare the clinical outcomes of BP-BES and DP-EES in real world cohorts of patients undergoing percutaneous coronary intervention. A prospective multicenter registry enrolled 999 patients treated with BP-BES and 1,000 patients treated with DP-EES. The primary outcome was target lesion failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or target lesion revascularization. Definite or probable stent thrombosis was also compared in total and propensity score-matched cohorts. The median follow-up duration was 24 months, and mean age was 65 years (interquartile range, 56-72 years). Patients receiving BP-BES had a lower prevalence of acute coronary syndrome, prior myocardial infarction, multi-vessel disease, bifurcation lesions, and left anterior descending artery lesions than those receiving DP-EES. After propensity score matching (692 pairs), target lesion failure occurred in 22 patients receiving BP-BES and in 25 patients receiving DP-EES (3.2% versus 3.6%; adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.53 to 1.60; p = 0.77). The risk of definite or probable stent thrombosis did not differ between the 2 groups (0.4% versus 0.4%; adjusted HR, 1.03; 95% CI, 0.21 to 4.98; p = 0.97). The results were consistent across various subgroups. In the propensity score-matched analysis of real world cohorts, BP-BES showed similar clinical outcomes compared to DP-EES. We need to investigate about whether differences in clinical outcome emerge during long-term follow-up.

Myocarditis is an inflammatory disease of the myocardium that causes cardiogenic shock and death. However, endomyocardial biopsy that is, the gold standard for a diagnosis is limited. Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a multifunctional protein, which is involved in DNA-based excision repair pathway, and in redox signaling, its changes are observed in various cardiovascular diseases including hypertension and coronary artery disease. We analyzed serum APE1/Ref-1 in experimental murine myocarditis. To induce myocarditis, coxsackievirus B3 was injected intraperitoneally to BALB/c mice. The serum APE1/Ref-1, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin I were measured. The histology and virus titers measurements were performed. The troponin I and inflammation were significantly elevated at day 3, peaked to day 7 and decreased at day 10. The NT-proBNP and virus titers were significantly peaked at day 3, and dropped at day 7 and 10. The serum APE1/Ref-1 was gradually raised and its elevation is still maintained until a later time, namely day 10. Also, its level was positively correlated with myocardial inflammation, reflecting severity of myocardial injury. We suggest that serum APE1/Ref-1 can be used to assess for myocardial injury in viral myocarditis without endomyocardial biopsy.

Familial hypercholesterolemia (FH) is a genetic disorder with an increased risk of early-onset coronary artery disease. Although some clinically diagnosed FH cases are caused by mutations in LDLR, APOB, or PCSK9, mutation detection rates and profiles can vary across ethnic groups. In this study, we aimed to provide insight into the spectrum of FH-causing mutations in Koreans. Among 136 patients referred for FH, 69 who met Simon Broome criteria with definite family history were enrolled. By whole-exome sequencing (WES) analysis, we confirmed that the 3 known FH-related genes accounted for genetic causes in 23 patients (33.3%). A substantial portion of the mutations (19 of 23 patients, 82.6%) resulted from 17 mutations and 2 copy number deletions in LDLR gene. Two mutations each in the APOB and PCSK9 genes were verified. Of these anomalies, two frameshift deletions in LDLR and one mutation in PCSK9 were identified as novel causative mutations. In particular, one novel mutation and copy number deletion were validated by co-segregation in their relatives. This study confirmed the utility of genetic diagnosis of FH through WES.

Vascular calcification plays a role in the pathogenesis of atherosclerosis, diabetes, and chronic kidney disease; however, the role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in inorganic phosphate (Pi)-induced vascular smooth muscle cell (VSMC) calcification remains unknown. In this study, we investigated the possible role of APE1/Ref-1 in Pi-induced VSMC calcification. We observed that Pi decreased endogenous APE1/Ref-1 expression and promoter activity in VSMCs, and that adenoviral overexpression of APE1/Ref-1 inhibited Pi-induced calcification in VSMCs and in an ex vivo organ culture of a rat aorta. However, a redox mutant of APE1/Ref-1(C65A/C93A) did not reduce Pi-induced calcification in VSMCs, suggesting APE1/Ref-1-mediated redox function against vascular calcification. Additionally, APE1/Ref-1 overexpression inhibited Pi-induced intracellular and mitochondrial reactive oxygen species production, and APE1/Ref-1 overexpression resulted in decreased Pi-induced lactate dehydrogenase activity, pro-apoptotic Bax levels, and increased anti-apoptotic Bcl-2 protein levels. Furthermore, APE1/Ref-1 inhibited Pi-induced osteoblastic differentiation associated with alkaline phosphatase activity and inhibited Pi-exposure-induced loss of the smooth muscle phenotype. Our findings provided valuable insights into the redox function of APE1/Ref-1 in preventing Pi-induced VSMC calcification by inhibiting oxidative stress and osteoblastic differentiation, resulting in prevention of altered osteoblastic phenotypes in VSMCs.

Clinical practice guidelines have been slowly and inconsistently applied in clinical practice, and certain evidence-based, guideline-driven therapies for heart failure (HF) have been significantly underused. The purpose of this study was to survey guideline compliance and its effect on clinical outcomes in the treatment of systolic HF in Korea.The SUrvey of Guideline Adherence for Treatment of Systolic Heart Failure in Real World (SUGAR) trial was a multi-center, retrospective, observational study on subjects with systolic HF (ejection fraction

BACKGROUND: The RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention) demonstrated that intravascular imaging--guided percutaneous coronary intervention (PCI) improved clinical outcome compared with angiography-guided PCI for patients with complex coronary artery lesions. This study aims to assess whether the prognostic benefit of intravascular imaging--guided procedural optimization persists in patients undergoing PCI for left main coronary artery disease. METHODS: Of 1639 patients enrolled in the RENOVATE-COMPLEX-PCI, 192 patients with left main coronary artery disease were selected for the current prespecified substudy. Selected patients were randomly assigned to either the intravascular imaging--guided PCI group (n=138) or the angiography-guided PCI group (n=54). The primary end point was target vessel failure defined as a composite of cardiac death, target vessel--related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: At a median follow-up of 2.1 years (interquartile range 1.1 to 3.0 years), intravascular imaging--guided PCI was associated with lower incidence of primary end point compared with angiography-guided PCI (6.8% versus 25.1%; hazard ratio, 0.31 [95% CI, 0.13-0.76]; P=0.010). This significant reduction in primary end point was mainly driven by a lower risk of cardiac death or spontaneous target vessel--related myocardial infarction (1.6% versus 12.7%; hazard ratio, 0.16 [95% CI, 0.03-0.82]; P=0.028). Intravascular imaging--guided PCI was independently associated with a lower risk of primary end point, even after adjusting for various clinical factors (hazard ratio, 0.29 [95% CI, 0.12-0.72]; P=0.007). CONCLUSIONS: Intravascular imaging--guided PCI showed clinical benefit over angiography-guided PCI for left main coronary artery disease in reducing the risk of cardiac death, target vessel--related myocardial infarction, or target vessel revascularization. [ABSTRACT FROM AUTHOR]