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A significant mismatch between proximal and distal reference lumen diameters of the target lesion may pose challenges during percutaneous coronary intervention (PCI) and therefore influence the outcomes. We investigated total 1706 lesions underwent IVUS guided percutaneous coronary intervention, that were divided into 2 groups, including 411 lesions in Mismatch group and 1295 lesions in Non-Mismatch group. After propensity score matching, 397 lesions in each group were selected for final data set. The analysis showed that Mismatch group PCI required more frequently use of post-stenting optimization (79.6% vs 53.9%, P < .001) using higher max pressure (19.5 ± 3.9 vs 16.7 ± 3.7 atm, P < .001). Besides, Mismatch group also encountered more PCI major complications (7.8% vs 4.0%, P = .024) and lower procedure success rate (91.4% vs 95.5%, P = .022). On final angiogram, Mismatch group had smaller minimum lumen diameter (2.62 ± .45 vs 2.90 ± .57 mm, P < .001) and lower angiographic success rate (93.2% vs 96.7%, P = .023). On final IVUS, Mismatch group had higher rate of incomplete stent apposition and stent edge dissection (6.3% vs 3.0%, P = .029 and 2.5% vs .5%, P = .021, respectively). In conclusion, reference mismatch posed significant challenging during PCI that led to unfavorable procedural outcomes. These impacts may translate into long-term clinical implications that need to be addressed in future studies.

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 Insulin and insulin-like growth factor 1 (IGF-1) signaling regulate cellular growth and glucose metabolism in the myocardium. However, their physiological role in cardiac conduction cells has never been explored. Therefore, we sought to determine the spatiotemporal function of insulin/IGF-1 receptors in the sinoatrial node (SAN). Methods We generated cardiac conduction cell-specific inducible IGF-1 receptor (IGF-1R) knockout (KO) (CSIGF1RKO), insulin receptor (IR) KO (CSIRKO), and IR/IGF-1R double KO (CSDIRKO) mice and evaluated their phenotypes. Results Telemetry measured electrocardiography found regular sinus rhythm in CSIGF1RKO mice, indicating that IGF-1R is dispensable for normal pacemaking. In contrast, CSIRKO and CSDIRKO mice exhibited profound sinus bradycardia. CSDIRKO mice showed a typical sinus node dysfunction characterized by junctional rhythm and sinus pauses on electrocardiography. Interestingly, the lack of an insulin receptor in the SAN cells of CSIRKO and CSDIRKO mice caused sinus nodal fibrosis. Mechanistically, hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) protein expression significantly decreased in the CSIRKO and CSDIRKO mice relative to the controls. A patch-clamp study of the SAN cells of CSIRKO mice marked a significant decrease in the funny current, which is responsible for spontaneous diastolic depolarization in the SAN. This result suggested that insulin receptor loss reduces the heart rate via downregulation of the HCN4 channel. Additionally, HCN1 expression was decreased in CSDIRKO mice explaining sinus node dysfunction. Conclusion Our results reveal a previously unrecognized insulin/IGF-1 signaling role in the sinus node structural maintenance and pacemaker function.

BACKGROUND: Moderate-intensity statin role with ezetimibe combination therapy following percutaneous coronary intervention (PCI) has not been thoroughly investigated, particularly compared to high-intensity statin monotherapy. We aimed to investigate the effect of ezetimibe combination with moderate-intensity statin in patients with atherosclerotic cardiovascular disease following PCI. METHODS: This was a post-hoc analysis of a subset of patients who underwent PCI in the RACING trial. At 26 centres in South Korea, patients with atherosclerotic cardiovascular disease (ASCVD) were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The prespecified endpoints of the RACING trial were used. The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, and nonfatal stroke. Event rates between the two groups were compared using log-rank tests, and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox regression analysis. Consistent with the RACING trial, the primary and secondary efficacy endpoints were evaluated using an intention-to-treatment approach, and the safety endpoints were assessed in the safety population. The RACING trial was registered at ClinicalTrials.gov (NCT03044665). FINDINGS: Between Feb 14, 2017, and Dec 18, 2018, 3780 participants were enrolled in the RACING trial. Prior history of PCI was found in 2497 patients (67%, median 64 years, 79% male), and was associated with higher rates of the primary endpoint (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.06–1.69; p = 0.014). Among patients with prior PCI, moderate-intensity statin therapy with ezetimibe combination versus high-intensity statin therapy did not increase the risk of the primary endpoint (HR, 0.95; 95% CI, 0.74–1.24; p = 0.781). The proportion of patients with low-density lipoprotein cholesterol (LDL-C)

Background: It remains unclear whether P2Y 12 monotherapy, especially clopidogrel, following short-duration dual antiplatelet therapy (DAPT) is associated with favorable outcomes in patients undergoing complex percutaneous coronary intervention (PCI). Therefore, this study analyzed the efficacy and safety of P2Y 12 inhibitor monotherapy, mostly clopidogrel (78%), in complex PCI following short-term DAPT. Methods: The post-hoc analysis of the SMART-CHOICE trial involving 2,993 patients included 498 cases of complex PCIs, defined by at least one of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with ≥ 2 stents implanted, and a total stent length of ≥ 60 mm. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as the composite of all-cause death, myocardial infarction, and stroke. The primary safety endpoint included bleeding, defined as Bleeding Academic Research Consortium (BARC) types 2 to 5. Results: Complex PCI group had a higher risk of MACCE (4.0% vs. 2.3%, hazard ratio [HR] = 1.74, 95% confidence interval [CI]: 1.05–2.89, p = 0.033) and a similar risk of BARC types 2–5 bleeding (2.6% vs. 2.6%, HR = 1.02, 95% CI: 0.56–1.86, p = 0.939) compared with those without complex PCIs. Patients undergoing complex PCIs, followed by P2Y 12 inhibitor monotherapy and 12 months of DAPT exhibited similar rates of MACCE (3.8% vs. 4.2%, HR = 0.92, 95% CI: 0.38–2.21, p = 0.853). Conclusions: P2Y 12 inhibitor monotherapy, mostly clopidogrel, following 3 months of DAPT did not increase ischemic events in patients with complex PCIs.

In this study, the use of shear strength ratio (SSR) in analysing asphalt mixture’s susceptibility to moisture was investigated and verified. Three surface and two base mixtures were considered for...

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

ObjectiveTo compare P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) with 12-month DAPT according to the type of P2Y12 inhibitor in patients undergoing percutaneous coronary intervention (PCI).MethodsThe Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) randomised trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT. In this trial, 2993 patients undergoing successful PCI with drug-eluting stent were enrolled in Korea. As a prespecified analysis, P2Y12 inhibitor monotherapy after 3-month DAPT versus 12-month DAPT were compared among patients receiving clopidogrel and those receiving potent P2Y12 inhibitor (ticagrelor or prasugrel), respectively. The primary endpoint was a composite of all-cause death, myocardial infarction or stroke at 12 months after the index procedure.ResultsAmong 2993 patients (mean age 64 years), 58.2% presented with acute coronary syndrome. Clopidogrel was prescribed in 2312 patients (77.2%) and a potent P2Y12 inhibitor in 681 (22.8%). There were no significant differences in the primary endpoint between the P2Y12 inhibitor monotherapy group and the DAPT group among patients receiving clopidogrel (3.0% vs 3.0%; HR: 1.02; 95% CI 0.64 to 1.65; p=0.93) as well as among patients receiving potent P2Y12 inhibitors (2.4% vs 0.7%; HR: 3.37; 95% CI 0.77 to 14.78; p=0.11; interaction p=0.1). Among patients receiving clopidogrel, P2Y12 inhibitor monotherapy compared with DAPT showed consistent treatment effects across various subgroups for the primary endpoint. Among patients receiving potent P2Y12 inhibitors, the rate of bleeding (Bleeding Academic Research Consortium types 2– 5) was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (1.5% vs 5.0%; HR: 0.33; 95% CI 0.12 to 0.87; p=0.03).ConclusionsCompared with 12-month DAPT, clopidogrel monotherapy after 3-month DAPT showed comparable cardiovascular outcomes in patients undergoing PCI.Trial registration numberNCT02079194.

OBJECTIVES To identify whether the prognostic implications of Vasoactive Inotropic Score according to use of mechanical circulatory support differ in the treatment of acute myocardial infarction complicated by cardiogenic shock. DESIGN A multicenter retrospective and prospective observational cohort study. SETTING/PATIENT The REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy registry includes 1,247 patients with cardiogenic shock from 12 centers in Korea. A total of 836 patients with acute myocardial infarction complicated by cardiogenic shock were finally selected, and the study population was stratified by quartiles of Vasoactive Inotropic Score ( 90) for the present study. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Primary endpoint was in-hospital mortality and secondary endpoint was follow-up mortality. Among the study population, 326 patients (39.0%) received medical treatment alone, 218 (26.1%) received intra-aortic balloon pump, and 292 (34.9%) received extracorporeal membrane oxygenation. In-hospital mortality occurred in 305 patients (36.5%) and was significantly higher in patients with higher Vasoactive Inotropic Score (15.6%, 20.8%, 40.2%, and 67.3%, for 90; p < 0.001). Vasoactive Inotropic Score showed better ability to predict in-hospital mortality in acute myocardial infarction patients with cardiogenic shock who received medical treatment alone (area under the curve: 0.797; 95% CI, 0.728-0.865) than in those who received intra-aortic balloon pump (area under the curve, 0.704; 95% CI, 0.625-0.783) or extracorporeal membrane oxygenation (area under the curve, 0.644; 95% CI, 0.580-0.709). The best cutoff value of Vasoactive Inotropic Score for the prediction of in-hospital mortality also differed according to the use of mechanical circulatory support (16.5, 40.1, and 84.0 for medical treatment alone, intra-aortic balloon pump, and extracorporeal membrane oxygenation, respectively). There was a significant interaction between Vasoactive Inotropic Score as a continuous value and the use of mechanical circulatory support including intra-aortic balloon pump (interaction-p = 0.006) and extracorporeal membrane oxygenation (interaction-p < 0.001) for all-cause mortality during follow-up. CONCLUSIONS High Vasoactive Inotropic Score was associated with significantly higher in-hospital and follow-up mortality in patients with acute myocardial infarction complicated by cardiogenic shock. The predictive value of Vasoactive Inotropic Score for mortality was significantly higher in acute myocardial infarction patients with cardiogenic shock treated by medical treatment alone than in those treated by mechanical circulatory support such as intra-aortic balloon pump or extracorporeal membrane oxygenation.

To describe the prevalence and associated factors of pre-frailty and frailty in older patients with heart failure.Secondary analysis of data collected across two cross-sectional surveys on self-care behaviours of patients with heart failure.We analysed the data of patients with heart failure who were 60 years or older (n = 407) in cardiovascular outpatient clinics at two tertiary medical centres in South Korea between 2018 and 2019. Frailty was evaluated using the Korean version of the 5-item fatigue, resistance, ambulation, illnesses and loss of weight (FRAIL) scale. Frailty status was categorized as robust, pre-frail and frail. Multivariate multinomial logistic regression was used to examine the associations between sociodemographic, clinical characteristics and frailty status.In our sample, the prevalence of pre-frailty and frailty was 45.6% and 28.3% respectively. Patients aged 80 years or older had a higher prevalence of pre-frailty and frailty than those younger than 80 years. Advanced age and the worst category in the New York Heart Association (NYHA) functional classification were significantly associated with the risk of pre-frailty and frailty. Additionally, having more comorbid conditions was associated with an increased risk of frailty.Our study identified advanced age, the NYHA functional classification, and the number of comorbidities as the major characteristics associated with the risk of frailty in older patients with heart failure.The findings of this study highlight the prevalence and associated characteristics of pre-frailty and frailty in older adults with heart failure in South Korea. Most older adults with heart failure were either pre-frail or frail. Advanced age, the NYHA functional classification, and the number of comorbidities were the major characteristics associated with frailty risk. Our findings highlight the importance of incorporating frailty screening into routine assessments in older patients with heart failure.

Coronary artery calcium score (CACS) is associated with increased risk of atrial fibrillation (AF). However, the relationship between the burden of CACS and extra-coronary calcium and the AF is unclear. This cross-sectional study retrospectively analyzed the data of 143,529 participants (74.9% men; mean age, 41.7 ± 8.6 years) who underwent health examination including non-contrast cardiac CT and electrocardiography, from 2010 to 2018 to evaluate the association between cardiac calcium and AF. AF was diagnosed in 679 participants. The prevalence of AF was significantly increased as the CACS increased (p < 0.01). Multivariable analysis adjusted for age, sex, body mass index, hypertension, diabetes, hyperlipidemia, smoking, alcohol, and history of coronary artery disease showed a significant association between a high CACS ≥1000 and AF (OR 2.26, 95% CI 1.07–4.77, p = 0.032). In a subgroup analysis of participants with a CACS ≥100, aortic valve and thoracic aorta calcium were significantly associated with AF (OR 3.49, 95% CI 1.57–7.77, p = 0.002 and OR 2.19, 95% CI 1.14–4.21, p = 0.01, respectively). High CACS was associated with AF, and extra-coronary atherosclerosis was associated with AF in participants with a moderate to very high CACS.

Objectives We 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). Methods A 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. Results During 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. Conclusions After 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.

Although the presence of hyperglycemia has been shown to affect the clinical outcome of patients with cardiogenic shock, the extent of hyperglycemia and its association with prognosis have not been fully addressed in a large population. A total of 1,177 consecutive patients with cardiogenic shock were enrolled from January 2014 to December 2018 at 12 hospitals in South Korea. The primary outcome was in-hospital mortality. Patients were divided into 4 groups according to their initial plasma glucose level in patients with diabetes mellitus (DM) (n = 752) and patients without DM (n=425); group 1 (≤8 mmol/L or 144 mg/100 ml), group 2 (8 to 12 mmol/L or 144 to 216 mg/100 ml), group 3 (12 to 16 mmol/L or 216 to 288 mg/100 ml), and group 4 (≥16 mmol/L or 288 mg/100 ml). The groups with higher admission plasma glucose were associated with lower systolic blood pressure and higher lactic acid levels in patients with and without DM. In-hospital mortality increased in groups with higher admission plasma glucose level in patients without DM (group 1:24.2%, group 2: 28.6%, group 3: 38.1%, group 4: 49.0%, p0.01), whereas in patients with DM, mortality and admission plasma glucose level showed no significant association (group 1: 45%, group 2: 35.4%, group 3: 33.3%, group 4: 43.1%, p = 0.26). Even after multivariate analysis, high plasma glucose was an independent predictor of in-hospital mortality in patients without DM. In patients with cardiogenic shock, plasma glucose obtained at admission was associated with in-hospital mortality in patients without DM.

NAD(P)H:quinone oxidoreductase (NQO) is an antioxidant flavoprotein that catalyzes the reduction of highly reactive quinone metabolites by employing NAD(P)H as an electron donor. There are two NQO enzymes—NQO1 and NQO2—in mammalian systems. In particular, NQO1 exerts many biological activities, including antioxidant activities, anti-inflammatory effects, and interactions with tumor suppressors. Moreover, several recent studies have revealed the promising roles of NQO1 in protecting against cardiovascular damage and related diseases, such as dyslipidemia, atherosclerosis, insulin resistance, and metabolic syndrome. In this review, we discuss recent developments in the molecular regulation and biochemical properties of NQO1, and describe the potential beneficial roles of NQO1 in diseases associated with oxidative stress.

ImportanceAlthough P2Y12 inhibitor monotherapy after a minimum period of dual antiplatelet therapy (DAPT) is a well-known way to reduce the risk of bleeding after percutaneous coronary intervention (PCI), data comparing long-term clinical outcomes between P2Y12 inhibitor monotherapy and extended DAPT in patients undergoing PCI have been unavailable.ObjectiveTo identify the long-term safety and efficacy of P2Y12 inhibitor monotherapy following 3 months of DAPT after PCI.Design, Setting, and ParticipantsThe Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy and Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) trial was an open-label, noninferiority, randomized clinical trial, enrolling patients who underwent PCI with drug-eluting stent at 33 hospitals in Korea from March 2014 through July 2017. Clinical follow-up was extended to 3 years and completed in August 2020.InterventionsPatients were randomly assigned to either P2Y12 inhibitor monotherapy after 3 months of DAPT or DAPT for 12 months or longer.Main Outcomes and MeasuresThe primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 3 years. The secondary end points included the components of the primary end point, bleeding (defined as Bleeding Academic Research Consortium [BARC] types 2-5), and major bleeding (BARC types 3-5).ResultsIn total, 2993 patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (1495 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1087 [72.7%] male) or prolonged DAPT (1498 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1111 [74.2%] male) after PCI. At 3 years, the primary end point occurred in 87 individuals (6.3%) in the P2Y12 inhibitor monotherapy group and 83 (6.1%) in the prolonged DAPT group (hazard ratio [HR], 1.06 [95% CI, 0.79-1.44]; P = .69). P2Y12 inhibitor monotherapy significantly reduced the risk of bleeding (BARC types 2-5: 112 [3.2%] vs 44 [8.2%]; HR, 0.39 [95% CI, 0.28-0.55]; P P = .048), compared with prolonged DAPT. The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.Conclusions and RelevanceAmong patients who underwent PCI and completed 3-month DAPT, P2Y12 inhibitor monotherapy was associated with a lower risk of clinically relevant major bleeding than prolonged DAPT. Although the 3-year risk of ischemic cardiovascular events was comparable between the 2 groups, this result should be interpreted with caution owing to the limited number of events and sample size.Trial RegistrationClinicalTrials.gov Identifier: NCT02079194

The insulin-like growth factor 1 receptor (IGF-1R) signaling in cardiomyocytes is implicated in physiological hypertrophy and myocardial aging. Although fibroblasts account for a small amount of the heart, they are activated when the heart is damaged to promote cardiac remodeling. However, the role of IGF-1R signaling in cardiac fibroblasts is still unknown. In this study, we investigated the roles of IGF-1 signaling during agonist-induced cardiac fibrosis and evaluated the molecular mechanisms in cultured cardiac fibroblasts. Using an experimental model of cardiac fibrosis with angiotensin II/phenylephrine (AngII/PE) infusion, we found severe interstitial fibrosis in the AngII/PE infused myofibroblast-specific IGF-1R knockout mice compared to the wild-type mice. In contrast, low-dose IGF-1 infusion markedly attenuated AngII-induced cardiac fibrosis by inhibiting fibroblast proliferation and differentiation. Mechanistically, we demonstrated that IGF-1-attenuated AngII-induced cardiac fibrosis through the Akt pathway and through suppression of rho-associated coiled-coil containing kinases (ROCK)2-mediated α-smooth muscle actin (αSMA) expression. Our study highlights a novel function of the IGF-1/IGF-1R signaling in agonist-induced cardiac fibrosis. We propose that low-dose IGF-1 may be an efficacious therapeutic avenue against cardiac fibrosis.

Objectives:To evaluate the angiographic and intravascular ultrasound (IVUS) characteristics of coronary mismatch lesions.Background:Better understanding about the characteristics of mismatch lesions may help to achieve more accurate lesion assessment and, thereby, to improve the outcomes of percutaneous coronary intervention (PCI).Methods:Angiographic and IVUS data from 1369 lesions were analyzed. Mismatch lesion was defined as the difference between proximal and distal reference lumen diameters of ≥1.0 mm or ≥30% of the distal reference lumen diameter.Results:The incidence of mismatch lesions was 20.1% (275/1369). Compared to nonmismatch group, mismatch group had longer lesions (21.3 [6.4] mm vs 18.4 [6.4] mm, P < .001) with smaller minimum lumen diameter (0.87 [0.29] mm vs 1.10 [0.31] mm, P < .001) and more severe diameter stenosis (78.8% [9.2%] vs 66.3% [10.3%], P < .001). On IVUS, mismatch group had larger lumen area (18.7 [5.0] vs 15.8 [5.1] mm2, P < .001) but lower plaque burden at the proximal reference segment (41.0% [9.2%] vs 45.7% [9.9%], P < .001) and smaller lumen area (4.83 [1.89] vs 7.36 [2.89] mm, P < .001) but higher plaque burden at the distal reference segment (42.9% [10.4%] vs 41.4% [10.1%], P = .023). Multivariable logistic regression analysis showed that mismatch lesions were frequently accompanied by diffuse lesions (odds ratio [OR] = 2.50; 95% confidence interval [CI]: 1.83-3.40; P < .001), bifurcation lesions (OR = 5.83; 95% CI: 4.40-7.74; P < .001), and lesions with a low TIMI flow grade (OR = 1.70; 95% CI: 1.08-2.67; P = .022) or severe diameter stenosis (OR = 3.05; 95% CI: 2.10-4.43; P < .001).Conclusions:Mismatch lesions are quite common and characterized by greater lesion complexity compared with nonmismatch lesions. Further studies may be necessary to address the impact of this lesion type on the outcome of PCI.

Background The benefits and risks of prolonged dual antiplatelet therapy (DAPT) have not been studied extensively across a broad spectrum of acute coronary syndromes. In this study we investigated whether treatment effects of prolonged DAPT were consistent in patients presenting with ST-segment elevation myocardial infarction (STEMI) vs. non-STEMI (NSTEMI).Methods and Results:As a post hoc analysis of the SMART-DATE trial, effects of ≥12 vs. 6 months DAPT were compared among 1,023 patients presenting with STEMI and 853 NSTEMI patients. The primary outcome was a composite of recurrent myocardial infarction (MI) or stent thrombosis at 18 months after the index procedure. Compared with the 6-month DAPT group, the rate of the composite endpoint was significantly lower in the ≥12-month DAPT group (1.2% vs. 3.8%; hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.12-0.77; P=0.012). The treatment effect of ≥12- vs. 6-month DAPT on the composite endpoint was consistent among NSTEMI patients (0.2% vs. 1.2%, respectively; HR 0.20, 95% CI 0.02-1.70; P=0.140; Pinteraction=0.718). In addition, ≥12-month DAPT increased Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding among both STEMI (4.4% vs. 2.0%; HR 2.18, 95% CI 1.03-4.60; P=0.041) and NSTEMI (5.1% vs. 2.2%; HR 2.37, 95% CI 1.08-5.17; P=0.031; Pinteraction=0.885) patients. Conclusions Compared with 6-month DAPT, ≥12-month DAPT reduced recurrent MI or stent thrombosis regardless of the type of MI at presentation.

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.

Although both angiotensin receptor blockers (ARBs) and dihydropyridine calcium channel blockers (CCBs) are all suitable for the initiation of antihypertensive treatment, studies investigating efficacy and safety between ARBs and CCBs are limited, and there is no previous study comparing their clinical outcomes during long-term follow-up periods in real world setting. We compared cardiovascular (CV) events between ARBs and CCBs in 464,948 hypertensive adults using the Korean National Health Insurance Service database during a 3-year follow-up. The patients with hypertension without heart failure, ischemic heart disease, cerebrovascular disease, or peripheral artery disease were enrolled. The CV events between only single prescription of CCBs and ARBs were finally compared. The primary endpoint for this study was the first occurrence of a major adverse CV events, defined as the composite of all-cause death, cardiac death, nonfatal myocardial infarction, or nonfatal stroke. ARB was significantly more administered in male and patients with higher income, diabetes mellitus, chronic kidney diseases, and higher Charlson comorbidity index. The primary endpoints occurred in 10,526 patients (5.2%) in the ARB group and in 19,363 patients (7.3%) in the CCB group (p

Background: In the current era of mechanical circulatory support, limited data are available on prognosis of cardiogenic shock (CS) caused by various diseases. We investigated the characteristics and predictors of in-hospital mortality in Korean patients with CS. Methods: The RESCUE study (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With CS) is a multicenter, retrospective, and prospective registry of patients that presented with CS. Between January 2014 and December 2018, 1247 patients with CS were enrolled from 12 major centers in Korea. The primary outcome was in-hospital mortality. Results: In-hospital mortality rate was 33.6%. The main causes of shock were ischemic heart disease (80.7%), dilated cardiomyopathy (6.1%), myocarditis (3.2%), and nonischemic ventricular arrhythmia (2.5%). Vasopressors were used in 1081 patients (86.7%). The most frequently used vasopressor was dopamine (63.4%) followed by norepinephrine (57.3%). An intraaortic balloon pump was used in 314 patients (25.2%) and extracorporeal membrane oxygenator in 496 patients (39.8%). In multivariable analysis, age ≥70years (odds ratio [OR], 2.73 [95% CI, 1.89–3.94], P 2 (OR, 1.52 [95% CI, 1.08–2.16], P =0.017), cardiac arrest at presentation (OR, 2.16 [95% CI, 1.44–3.23], P 80 (OR, 3.55 [95% CI, 2.54–4.95], P P P P =0.020), and extracorporeal membrane oxygenator (OR, 1.85 [95% CI, 1.25–2.76], P =0.002) were independent predictors for in-hospital mortality. Conclusions: The in-hospital mortality of patients with CS remains high despite the high utilization of mechanical circulatory support. Age, low body mass index, cardiac arrest at presentation, amount of vasopressor, and advanced organ failure requiring various support devices were poor prognostic factors for in-hospital mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02985008.

Background: Although the current guidelines endorse the PRECISE-DAPT score (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) to inform clinical decisions regarding duration of DAPT in patients undergoing percutaneous coronary intervention, use of the PRECISE-DAPT score to guide duration of DAPT has not been properly validated by randomized trials focused on the population with acute coronary syndrome. This study aimed to evaluate the usefulness of the PRECISE-DAPT score for predicting future bleeding and ischemic events and to compare clinical outcomes of short-term and long-term DAPT duration according to the PRECISE-DAPT score in patients with acute coronary syndrome. Methods: This was a substudy of the SMART-DATE trial (6- Versus 12-Month or Longer Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome), in which patients with acute coronary syndrome undergoing percutaneous coronary intervention were randomly assigned to either 6- (n=1357) or 12-month or longer DAPT (n=1355). Major bleeding (Bleeding Academic Research Consortium type 3–5) and ischemic (myocardial infarction, stent thrombosis, or ischemic stroke) events at 18 months after the index procedure were compared between the 6- and 12-month or longer DAPT groups, according to PRECISE-DAPT score. Results: The PRECISE-DAPT score was moderately effective at predicting bleeding events (area under the curve, 0.754 [95% CI, 0.655–0.854]; P P =0.040; absolute risk difference, +1.3%; P =0.035) with similar bleeding risk (0.4% versus 0.3%; HR, 2.00 [95% CI, 0.37–10.94]; P =0.422; absolute risk difference, +0.2%; P =0.498), compared with 12-month or longer DAPT. Among patients with high PRECISE-DAPT score (≥25, n=745 [27.5%]), 6-month DAPT presented a similar ischemic risk (4.8% versus 3.4%; HR, 1.43 [95% CI, 0.68–2.98], P =0.348; absolute risk difference, +1.5%; P =0.327) but significantly reduced major bleeding risk (0.6% versus 2.3%; HR, 0.25 [95% CI, 0.05–1.17]; P =0.079; absolute risk difference, −1.7%; P =0.045). Conclusions: Consistent with current guidelines, determination of the duration of DAPT according to PRECISE-DAPT score could improve the clinical outcomes in patients with acute coronary syndrome after percutaneous coronary intervention with current-generation drug-eluting stents. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01701453.

Purpose Little is known about ethnic differences in the size of coronary arteries in disease-free individuals. Our aim was to compare coronary artery dimensions between Asian and Caucasian population without atherosclerosis. Methods One hundred and twelve Caucasian patients without any discernible atherosclerosis detected on coronary computed tomography angiography were matched with 112 Asian patients using sex, age, coronary dominance pattern and body surface area (BSA). Maximal and minimal lumen areas (LA) and diameters (LD) of proximal and middle coronary segments were measured, and the mean values were used for analyses. Results Caucasians had larger LA and LD than Asian patients in all proximal coronary segments. Overall, the mean difference in LA and LD was 11.4 % and 5.2 %, respectively. Significant differences were observed for all proximal segments (left anterior descending: 13 % and 6%, left circumflex 14 % and 8% and right coronary artery 8% and 4% for LA and LD), but not for mid segments. The greatest difference between Caucasians and Asians was found in left main coronary artery (LMCA) LA (21.2 ± 6.5 vs.16.8 ± 5.4 mm2, p Conclusion In subjects without atherosclerosis, Asians have smaller dimensions of all proximal coronary arteries, most prominently displayed in LMCA, than the Caucasians regardless of age, sex, or body size.

Even cardiac surgery has been accepted as the standard therapy for Lutembacher syndrome, a combination of congenital ostium secundum atrial septal defect (ASD) and acquired mitral valve stenosis (MVS), it also owns many limitations and disadvantages. Therefore, seeking for a less invasive therapy with the same efficacy may be worthwhile. Thanks to the development in technology and experience gaining in cardiovascular intervention, the combination of the two proved effective procedures, including percutaneous MVS treatment using balloon valvuloplasty and percutaneous ASD closure using atrial septal occluders, can be utilized as an attractive alternative therapy for these conditions. Here, we present a successful percutaneous intervention in Lutembacher syndrome using the combination of mitral balloon valvuloplasty and ASD device closure and thoroughly review the experience of using this combined procedure existing in the literature.

The development of risk assessment methods for depression and cave-in caused by subsurface cavity in the asphalt pavement is presented. Pavement response models and risk factor concept were used in...

Tyrosine kinase inhibitors (TKIs) have shown clear survival benefits as effective targeted therapies in various hematological and solid malignancies. Important evidence, however, has shown that TKIs may lead to adverse effects such as cardiovascular toxicities, via off-target as well as on-target mechanisms. This review presents an overview of TKI-induced cardiotoxicity mechanisms, clinical manifestations, diagnosis, monitoring, and management options. Furthermore, we discuss current preclinical efforts and future investigations into alternative therapeutics for minimizing the cardiotoxicities associated with tyrosine kinase-targeted therapies. Accompanying with the significant improvements toward targeted anticancer treatment, cardiotoxicity-related adverse effects are increasingly reported and have become an important public health issue. The TKI-induced cardiovascular toxicities include myocardial ischemia, heart failure, QT prolongation, and hypertension. Thus, the early awareness of cardiotoxicities, initiation of appropriate management, and close follow-up, may enhance the benefits of TKI therapy.

Cardiovascular disease (CVD) is the leading cause of death in most developed countries. Aging is associated with enhanced risk of CVD. Insulin-like growth factor-1 (IGF-1) binds to its cognate receptor, IGF-1 receptor (IGF-1R), and exerts pleiotropic effects on cell growth, differentiation, development, and tissue repair. Importantly, IGF-1/IGF-1R signaling is implicated in cardiac aging and longevity. Cardiac aging is an intrinsic process that results in cardiac dysfunction, accompanied by molecular and cellular changes. In this review, we summarize the current state of knowledge regarding the link between the IGF-1/IGF-1R system and cardiac aging. The biological effects of IGF-1R and insulin receptor will be discussed and compared. Furthermore, we describe data regarding how deletion of IGF-1R in cardiomyocytes of aged knockout mice may delay the development of senescence-associated myocardial pathologies. This article is part of a Special issue entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.

Salicylates, one of the oldest medicinal compounds known to humans, have been reported to show anti-inflammatory effects via cyclooxygenase (COX) inhibition. However, the pathophysiological role of COX-2 in the heart is conflicting, and the role of sodium salicylate in the regulation of cardiac inflammation has not yet been elucidated. We aimed to investigate the effect of salicylate on COX-2 expression and its associated prostaglandin production using cultured neonatal rat cardiomyocytes. The cells were incubated in the presence or absence of sodium salicylate (8 mM). Treatment with sodium salicylate significantly increased COX-2 expression at both mRNA and protein levels, induced prostaglandin D2 release, and increased TNF-α mRNA expression in cardiomyocytes. In addition, salicylate treatment induced cardiomyocyte hypertrophy. Taken together, we demonstrated that salicylate induced COX-2 expression, which in turn resulted in the regulation of expression of several inflammatory mediators in cardiomyocytes.

In this paper, we propose a novel method for three-dimensional (3D) blood vessel modeling. Given the incomplete nature of medical images, a 3D blood vessel model that includes the intima and adventitia cannot be reconstructed with a single medical image. Intravascular ultrasound (IVUS) images are used to obtain detailed intimal and adventitial information. Then, X-ray angiogram images are used to calculate the position and orientation of IVUS images. Combining these medical images can generate a 3D blood vessel model. To visualize a blood vessel via IVUS, a catheter that is attached to a miniaturized ultrasound device is inserted into the blood vessel. The insertion of the catheter deforms the blood vessel. This deformation is reflected in the 3D blood vessel model that is developed from combining IVUS and X-ray angiogram images. To address this problem, we propose a novel method for 3D blood vessel modeling using undeformed intimal and adventitial information from IVUS images. Our proposed method has potential applications in hemodynamic analysis.