Atrial fibrillation de novo in acute coronary syndrome.

One of the complications during an acute coronary syndrome event is the presence of arrhythmias. Among them, those of the supraventricular type, especially atrial fibrillation, carry a poor prognosis both in the short and long term, being the cause of situations such as cerebrovascular event, ventricular arrhythmias, and increased mortality. The arrhythmia tends to appear in a certain population group with particular risk factors during the index event in approximately 10% of cases. Appropriate treatment at the time of its onset, thanks to the use of drugs that modulate heart rate, rhythm, and anticoagulant management in the most vulnerable groups, will lead to a less bleak outcome for these patients.

Una de las complicaciones durante un evento de síndrome coronario agudo es la presencia de arritmias. Dentro de ellas, las de tipo supraventricular, en especial fibrilación auricular, acarrea un mal pronóstico tanto a corto como a largo plazo y es la causa de situaciones como evento vascular cerebral, arritmias ventriculares y aumento de la mortalidad. Dicha arritmia tiende a aparecer en cierto grupo de población con particulares factores de riesgo durante el evento índice en aproximadamente 10% de los casos. Un tratamiento apropiado en el momento de su aparición, gracias al uso de fármacos que modulan la frecuencia cardiaca, el ritmo y el manejo anticoagulante en los grupos más vulnerables conllevará un desenlace menos sombrío para estos pacientes.

An update on the mechanisms of Takotsubo syndrome: "At the end an acute coronary syndrome".

Takotsubo syndrome (TTS) is an acute reversible form of myocardial dysfunction, often preceded by a physical or emotional stressful event, that acts as a trigger. Despite, recent advances in the comprehension of the mechanisms leading to TTS, its pathophysiology is far from being completely understood. However, several studies seem to suggest that an acute coronary microvascular dysfunction may represent a crucial pathogenic mechanism involved in TTS occurrence. In this article, we aim to review the complex pathophysiology of TTS and the possible different mechanisms underlying this clinical condition, focusing on the role of coronary microvascular dysfunction and the remaining knowledge's gaps in the field.

Sex differences in patients presenting with acute coronary syndrome: a state-of-the-art review.

Cardiovascular conditions in the spectrum of acute coronary syndromes are characterized by sex differences with regard to pathophysiology, risk factors, clinical presentation, invasive and pharmacologic treatment, and outcomes. This review delves into these differences, including specific subsets like myocardial infarction with non-obstructed coronary arteries or Spontaneous Coronary Artery Dissection, and alternative diagnoses like Takotsubo cardiomyopathy or myocarditis. Moreover, practical considerations are enclosed, on how a sex-specific approach should be integrated in clinical practice: in fact, personal history should focus on female-specific risk factors, and hormonal status and hormonal therapy should be assessed. Moreover, physical and psychological stressors should be investigated, particularly in the event of Spontaneous Coronary Artery Dissection or Takotsubo cardiomyopathy.

Acute coronary syndromes in patients with cancer: Recent advances.

Coronary artery disease is presently one of the leading causes of death among cancer survivors. Due to the number of cancer survivors projected to reach 26 million by 2040 managing coronary disease in this population presents a unique challenge. Cancer patients face an elevated risk of atherosclerotic disease due to shared cardiovascular risk factors and the cardiotoxic effects of cancer therapies, predisposing them to acute coronary syndromes. Challenges in treating cancer patients presenting with acute coronary syndromes include atypical presentations, obscured symptoms, and the impact of cancer-related processes on traditional biomarkers. This review explores the complexities of acute coronary syndrome management in cancer patients, addressing challenges involved, recent advances in percutaneous strategies, pharmacology, and considerations for these high-risk individuals. This review discusses a balance between invasive vs. medical strategy, technical advances in multimodal imaging, intravascular physiology, intracoronary imaging, and evolving stent options, highlighting the need for tailored approaches in this complex patient population.

Giant coronary sinus aneurysm: an incidental discovery in a case of acute coronary syndrome.

Coronary sinus (CS) anomalies, although infrequent, are increasingly diagnosed with advances in interventional procedures and imaging techniques. Most cases are asymptomatic and incidentally diagnosed. We present a case of an elderly male without comorbidities who presented with acute angina. Coronary catheterisation revealed a double-vessel disease, but incidentally, sequential angiograms captured contrast filling in the levophase of CS, revealing a giant CS. Primary percutaneous angioplasty of the right coronary artery was performed successfully. Echocardiography confirmed the aneurysm, and a CT scan showed an aneurysmally dilated CS and other coronary veins alongside a normal-sized persistent left superior vena cava draining to the right atrium through CS. CS aneurysms may lead to complications such as thrombosis, embolic events, arrhythmias and heart failure, stressing the importance of vigilant monitoring and timely intervention. This case underscores the significance of recognising CS anomalies in cardiac procedures, even when asymptomatic, for proper management.

Short-Term Changes in Weather Conditions and the Risk of Acute Coronary Syndrome Hospitalization with and without ST-Segment Elevation: A Focus on Vulnerable Subgroups.

Background and Objectives: Acute coronary syndrome (ACS), a prevalent global cardiovascular disease and leading cause of mortality, is significantly correlated with meteorological factors. This study aims to analyze the impact of short-term changes in meteorological factors on the risk of ACS, both with and without ST-segment elevation, and to identify vulnerable subgroups. Materials and Methods: Daily ACS admissions and meteorological variables were collected from October 2016 to December 2021. A generalized linear model (GLM) with a Poisson distribution was employed to examine how short-term fluctuations in meteorological parameters influence ACS hospitalizations. Subgroup analyses were conducted to identify the populations most vulnerable to climate change. Results: Multiple regression analyses showed that short-term fluctuations in atmospheric pressure (≥10 mbar) and air temperature (≥5 °C) seven days prior increased the number of ACS hospitalizations by 58.7% (RR: 1.587; 95% CI: 1.501-1.679) and 55.2% (RR: 1.552; 95% CI: 1.465-1.644), respectively, notably impacting ST-segment elevation myocardial infarctions (STEMIs). The least pronounced association was observed between the daily count of ACS and the variation in relative air humidity (≥20%), resulting in an 18.4% (RR: 1.184; 95% CI: 1.091-1.286) increase in the risk of hospitalization. Subgroup analysis revealed an increased susceptibility among men and older adults to short-term variations in weather parameters. Conclusions: The findings indicate that short-term changes in weather conditions are associated with an increased risk of ACS hospitalizations, particularly STEMIs. Male and older adult patients exhibit heightened susceptibility to variations in climatic factors. Developing effective preventive strategies is imperative to alleviate the adverse consequences of these environmental risk factors.

Impact of Red Blood Cell Transfusion on Subsequent Cardiovascular Events in Patients with Acute Heart Failure and Anemia.

Red blood cell (RBC) transfusion therapy is often performed in patients with acute heart failure (AHF) and anemia; however, its impact on subsequent cardiovascular events is unclear. We examined whether RBC transfusion influences major adverse cardiovascular events (MACE) after discharge in patients with AHF and anemia.We classified patients with AHF and anemia (nadir hemoglobin level < 10 g/dL) according to whether they received RBC transfusion during hospitalization. The endpoint was MACE (composite of all-cause death, non-fatal acute coronary syndrome/stroke, or heart failure readmission) 180 days after discharge. For survival analysis, we used propensity score matching analysis with the log-rank test. As sensitivity analysis, we performed inverse probability weighting analysis and multivariable Cox regression analysis.Among 448 patients with AHF and anemia (median age, 81 years; male, 55%), 155 received RBC transfusion and 293 did not. The transfused patients had worse clinical features than the non-transfused patients, with lower levels of nadir hemoglobin and serum albumin and a lower estimated glomerular filtration rate. In the propensity-matched cohort of 87 pairs, there was no significant difference in the MACE-free survival rate between the 2 groups (transfused, 73.8% vs. non-transfused, 65.3%; P = 0.317). This result was consistent in the inverse probability weighting analysis (transfused, 76.0% vs. non-transfused, 68.7%; P = 0.512), and RBC transfusion was not significantly associated with post-discharge MACE in the multivariable Cox regression analysis (adjusted hazard ratio: 1.468, 95% confidence interval: 0.976-2.207; P = 0.065).In conclusion, this study suggests that RBC transfusions for anemia may not improve clinical outcomes in patients with AHF.

Impact of inflammatory bowel disease on the risk of acute coronary syndrome: A Swedish Nationwide Cohort Study.

BACKGROUND: There are conflicting data on the risk of acute coronary syndrome (ACS) in patients with inflammatory bowel disease (IBD). Only a few previous reports include patients diagnosed during the last decade. AIM: To assess and compare the risk of ACS between patients with IBD and the general population. METHODS: In this cohort study, we used nationwide registers to identify patients diagnosed with IBD in Sweden 2003-2021. Every patient was matched by birth year, sex, calendar year and area of residence with up to 10 general population comparators. The primary outcome was incident ACS. We used semi-parametric Cox proportional hazard models to estimate hazard ratios (HRs). RESULTS: We identified 76,517 patients with IBD (Crohn's disease [CD], N = 22,732; ulcerative colitis [UC], N = 42,194 and IBD-unclassified, N = 11,591) and 757,141 comparators. During a median follow-up of 8 years, 2546 patients with IBD (37.5/10,000 person-years) were diagnosed with ACS compared with 19,598 (28.0/10,000 person-years) among comparators (HR 1.30; 95% confidence interval 1.24-1.35) after adjustments for confounding factors, and approximately one extra case of ACS in 100 IBD patients followed for 10 years. The highest HRs for ACS were in patients with elderly onset IBD (≥60 years) and among patients with CD or UC with extra-intestinal manifestations. No increased HRs were observed in patients diagnosed with IBD before the age of 40. CONCLUSION: In this contemporary cohort of patients with IBD, exposed to modern IBD care, there was an increased risk for ACS compared with individuals from the general population.

Prognostic value of Geriatric Nutritional Risk Index and systemic immune-inflammatory index in elderly patients with acute coronary syndromes.

The objective of this study was to evaluate the predictive value of the Geriatric Nutritional Risk Index (GNRI) combined with the Systemic Immunoinflammatory Index (SII) for the risk of major adverse cardiovascular events (MACE) following percutaneous coronary intervention in elderly patients with acute coronary syndrome (ACS). We retrospectively reviewed the medical records of 1202 elderly patients with acute coronary syndromes divided into MACE and non-MACE groups according to whether they had a MACE. The sensitivity analysis utilized advanced machine learning algorithms to preliminarily identify the critical role of GNRI versus SII in predicting MACE risk. We conducted a detailed analysis using a restricted cubic spline approach to investigate the nonlinear relationship between GNRI, SII, and MACE risk further. We constructed a clinical prediction model based on three key factors: GNRI, SII, and Age. To validate the accuracy and usefulness of this model, we compared it to the widely used GRACE score using subject work and recall curves. Additionally, we compared the predictive value of models and GRACE scores in assessing the risk of MACE using the Integrated Discriminant Improvement Index (IDI) and the Net Reclassification Index (NRI). This study included 827 patients. The GNRI scores were lower in the MACE group than in the non-MACE group, while the SII scores were higher in the MACE group (P < 0.001). The multifactorial analysis revealed a low GNRI (OR = 2.863, 95% CI: 2.026-4.047, P = 0.001), High SII (OR = 3.102, 95% CI: 2.213-4.348, P = 0.001). The area under the curve (AUC) for the predictive model was 0.778 (95% CI: 0.744-0.813, P = 0.001), while the AUC for the GRACE score was 0.744 (95% CI: 0.708-0.779, P = 0.001). NRI was calculated to be 0.5569, with NRI + at 0.1860 and NRI- at 0.3708. The IDI was found to be 0.0571, with a P-value of less than 0.001. These results suggest that the newly developed prediction model is more suitable for use with the population in this study than the GRACE score. The model constructed using GNRI and SII demonstrated good standardization and clinical impact, as evidenced by the standard, DCA, and clinical impact curves. The study shows that combining GNRI and SII can be a simple, cost-effective, and valuable way to predict the risk of MACE within one year in elderly acute coronary syndromes.

Effect of ticagrelor versus clopidogrel after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome-propensity score matching analysis.

BACKGROUND: The effect of different dual antiplatelet therapies on thrombotic events on the background of intravascular ultrasound (IVUS) guidance is unclear. We investigated whether ticagrelor can provide any additional benefit to clopidogrel in reducing thrombotic events in acute coronary syndrome (ACS) treated with drug- eluting stent (DES), when guided by IVUS or not. METHODS: A total of 5,666 ACS patients who underwent DES implantation and who were discharged on dual antiplatelet therapy were enrolled and grouped according to the use of IVUS or not. Each group was subdivided into two subgroups according to the type of P2Y12 inhibitor used after discharge. Propensity score matching (PSM) was used between the IVUS and no-IVUS groups. Covariate adjustment of Cox proportional hazards model was used between the ticagrelor and clopidogrel groups. Thrombotic event at 12 months was compared in groups separately. RESULTS: After PSM, 12-month follow-up data were available for 1,174 patients. Major adverse cardiac events (MACE) were less frequent in the IVUS-guided group (2.2% vs. 4.3%, P = 0.081) with a trend toward statistical significance. Comparison of antiplatelet regimens revealed significantly fewer major adverse cardiac and cerebrovascular events (MACCE) with ticagrelor in the entire PSM cohort and angiography-guided subgroup (2.9% vs. 5.7%, P = 0.035; 3.1% vs. 6.4%, P = 0.020, respectively). Among patients in the IVUS-guided group the outcome was comparable (2.5% vs. 4.4%, P = 0.312). Ticagrelor was associated with increasing bleeding incidence in the entire PSM cohort (1.3% vs. 3.3%, P = 0.030), mainly due to Bleeding Academic Research Consortium type 2 bleeding (0.7% vs. 2.6%, P = 0.010). The results were consistent after covariate adjustment of Cox proportional hazards model. CONCLUSION: The comparison of ischemic benefit between ticagrelor and clopidogrel was similar in patients receiving IVUS guidance during stent implantation, probably due to the precise implantation of IVUS. Multicenter, randomized studies should be performed to validate this conclusion.

Systemic immune inflammation index and its implication on in-stent restenosis among patients with acute coronary syndrome.

OBJECTIVE: This study aims to assess the predictive value of the Systemic Immune Inflammation Index (SII) in determining in-stent restenosis (ISR) likelihood in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI). METHODS: The study enrolled 903 ACS patients undergoing PCI, categorized into ISR (+) and ISR (-) groups based on control coronary angiography results. Demographic, clinical, laboratory, and angiographic-procedural characteristics were systematically compared. RESULTS: The ISR (+) group encompassed 264 individuals (29.2%), while the ISR (-) group comprised 639 individuals (70.8%). Patients had a mean age of 55.8 ±â€…10.2 years, with 69% being male. The ISR (+) group had higher diabetes and smoking prevalence and notably larger stent dimensions. Lab parameters showed significantly elevated creatinine, total cholesterol, red cell distribution width, white blood cell and neutrophil counts, SII index and C-reactive protein (CRP) in the ISR (+) group, while lymphocyte levels were lower. Binary logistic regression identified stent diameter (odds ratio [OR]: 0.598, 95% confidence interval [CI]: 0.383-0.935; P  = 0.024), stent length (OR: 1.166, 95% CI: 1.132-1.200; P  < 0.001), creatinine (OR: 0.366, 95% CI: 0.166-0.771; P  = 0.003), CRP (OR: 1.075, 95% CI: 1.042-1.110; P  = 0.031), and SII index (OR: 1.014, 95% CI: 1.001-1.023; P  < 0.001) as independent ISR predictors. CONCLUSION: The SII index exhibits potential as a predictive marker for ISR in ACS patients post-PCI, indicating systemic inflammation and heightened restenosis risk. Integrating the SII index into risk models could identify high-risk patients for targeted interventions.

Short-term air pollution exposure and mechanisms of plaque instability in acute coronary syndromes: An optical coherence tomography study.

BACKGROUND AND AIMS: Air pollution is emerging as an important risk factor for acute coronary syndrome (ACS). In this study, we investigated the association between short-term air pollution exposure and mechanisms of coronary plaque instability evaluated by optical coherence tomography (OCT) imaging in ACS patients. METHODS: Patients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT. Based on each case's home address, the mean daily exposures to several pollutants, including particulate matter 2.5 (PM2.5), on the same day of ACS and in the immediate days (up to 6 days) prior to the index ACS, were collected. RESULTS: 139 ACS patients were included [69 (49.6%) had PR and 70 (50.4%) IFC]. Patients with PR, compared to those with IFC, had higher PM2.5 exposure levels on the same day of ACS, without differences in the immediate 6 days before index ACS. At multivariate analysis, PM2.5 exposure on the same day of ACS was the only independent predictor of PR [OR = 1.912 per SD (8.6 µg/m3), CI95 % (1.087-3.364), p = 0.025]. Patients with PR presented a steady increase in PM2.5 daily exposure levels in the days preceding the occurrence of ACS, with a peak the day of ACS (p for trend = 0.042) CONCLUSIONS: This study demonstrates for the first time that a higher short-term PM2.5 exposure, on the same day of ACS, is associated with an increased risk of PR as a pathobiological mechanism of coronary plaque instability.

Recurrent events of acute coronary syndrome in young adult patients after Kawasaki disease.

OBJECTIVE: I encountered three adult patients with major coronary artery occlusion after Kawasaki disease in childhood, who had developed again acute coronary syndrome of adults in the peripheral branches, such as the 4th segments, the atrioventricular node artery, and the posterior descending artery, of the right coronary artery. METHODS: I reviewed their clinical course and coronary angiograms. RESULTS: Their age at onset of acute coronary syndrome ranged from 29 to 33 years. The male patient with a previous anteroseptal myocardial infarction in children had a symptomatic occlusion of the branch of the 4th posterior descending artery at 32 years of age. Acute coronary syndrome occurred in the area of 4th atrioventricular node artery in two female patients. The collateral arteries from the circumflex artery to the 4th atrioventricular node arteries were not clearly injected. It was suspected that they had developed bilateral giant aneurysms after acute Kawasaki disease. Two patients had an acute myocardial infarction due to thrombotic occlusion in a giant aneurysm of the right coronary artery or the left anterior descending artery, and one patient had an asymptomatic coronary occlusion of the right coronary artery and left anterior descending artery in children. CONCLUSION: Occlusion of peripheral coronary arteries in adulthood can occur in patients with multi-vessel disease caused by Kawasaki disease. Recurrent events of acute coronary syndrome can occur in adults, although its prevalence may be low. Careful follow-up in adults is also needed in this population.

A case of Behçet syndrome presenting with acute coronary syndrome.

Cardiac involvement (CI) is rare in Behçet syndrome (BS), but the important point is that CI may be the first manifestation of the disease. The presence of CI worsens the prognosis of BS, so early diagnosis and early initiation of immunosuppressive treatment (IST) are vital. Coronary aneurysm may develop spontaneously in these patients, or any vascular intervention may cause aneurysm with a pathergy-like reaction. The risk of restenosis is high after percutaneous coronary intervention or coronary artery bypass surgery applied without IST. Therefore, it should be kept in mind that IST constitutes the main step of treatment. Herein, we present a young male diagnosed with BS after acute coronary syndrome caused by coronary artery aneurysms and thrombosis.

Lipid Content Distribution and its Clinical Implication in Patients with Acute Myocardial Infarction-Plaque Erosion: Results from the Prospective OCTAMI Study.

AIMS: Plaque erosion (PE) is one of the main plaque phenotypes of acute coronary syndrome (ACS). However, the underlying plaque component and distribution have not been systematically analysed. This study aims to investigate the distribution of lipid and calcium content in culprit lesions assessed by optical coherence tomography (OCT) in patients with PE and explore its relationship with prognosis in a cohort of ST segment elevation myocardial infarction (STEMI) patients. METHODS: A prospective cohort of 576 patients with STEMI was enrolled in our study. After exclusion, 152 PE patients with clear underlying plaque components were ultimately analysed. The culprit lesion was divided into the border zone, external erosion zone and erosion site in the longitudinal view. Each pullback of the culprit lesions was assessed by 3 independent investigators frame-by-frame, and the quantity and distribution of lipid and calcium components were recorded. RESULTS: Of the 152 PE patients, lipid and calcium contents were more likely to exist in the external erosion zone than in the other regions. In particular, a high level of lipid content proximal to the erosion site was significantly associated with plaque vulnerability and a higher incidence of MACEs. CONCLUSION: This study revealed that high level of lipid content in the proximal external erosion zone was related to high-risk plaque characteristics and poor prognosis, which provided a novel method for risk stratification and precise management in patients with plaque erosion.

Switching from Dual Antiplatelet Therapy with Aspirin Plus a P2Y12 Inhibitor to Dual Pathway Inhibition with Aspirin Plus Vascular-Dose Rivaroxaban: The Switching Anti-Platelet and Anti-Coagulant Therapy (SWAP-AC) Study.

BACKGROUND: To date, there are no data on switching to dual pathway inhibition (DPI) patients who have completed a guideline-recommended dual antiplatelet therapy (DAPT) regimen. OBJECTIVES: To assess the feasibility of switching from DAPT to DPI and to compare the pharmacodynamic (PD) profiles of these treatments. METHODS: This was a prospective, randomized, PD study conducted in 90 patients with chronic coronary syndrome (CCS) on DAPT with aspirin (81 mg/qd) plus a P2Y12 inhibitor (clopidogrel [75 mg/qd; n = 30], ticagrelor [90 mg/bid; n = 30], or prasugrel [10 mg/qd; n = 30]). Patients in each cohort were randomized to maintain DAPT or switch to DPI (aspirin 81 mg/qd plus rivaroxaban 2.5 mg/bid). PD assessments included: VerifyNow P2Y12 reaction units; light transmittance aggregometry following stimuli with adenosine diphosphate (ADP), tissue factor (TF), and a combination of collagen, ADP, and TF (maximum platelet aggregation %); thrombin generation (TG). Assays were performed at baseline and 30 days postrandomization. RESULTS: Switching from DAPT to DPI occurred without major side effects. DAPT was associated with enhanced P2Y12 inhibition, while DPI with reduced TG. Platelet-mediated global thrombogenicity (primary endpoint) showed no differences between DAPT and DPI in the ticagrelor (14.5% [0.0-63.0] vs. 20.0% [0.0-70.0]; p = 0.477) and prasugrel (20.0% [0.0-66.0] vs. 4.0% [0.0-70.0]; p = 0.482), but not clopidogrel (27.0% [0.0-68.0] vs. 53.0% [0.0-81.0]; p = 0.011), cohorts. CONCLUSION: In patients with CCS, switching from different DAPT regimens to DPI was feasible, showing enhanced P2Y12 inhibition with DAPT and reduced TG with DPI, with no differences in platelet-mediated global thrombogenicity between DPI and ticagrelor- and prasugrel-, but not clopidogrel-, based DAPT. CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov Unique Identifier: NCT04006288.

Comparison among various physiology and angiography-guided strategies for deferring percutaneous coronary intervention: A network meta-analysis.

BACKGROUND/PURPOSE: It is unclear whether coronary physiology or coronary angiography (CA)-guided strategy is the more preferable approach for deferring percutaneous coronary intervention (PCI). We sought to evaluate the clinical efficacy of various PCI strategies through a network meta-analysis of randomized controlled trials (RCTs). METHODS/MATERIALS: We searched multiple databases for RCTs investigating the impact of the following strategies for the purpose of determining whether or not to defer PCI: fractional flow reserve, instantaneous wave-free ratio, quantitative flow ratio (QFR), and CA. We conducted a network meta-analysis for trial-defined major adverse cardiovascular events (MACE), all-cause death, cardiovascular death, myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis. We performed a subgroup analysis for those with acute coronary syndrome (ACS). RESULTS: Our search identified 12 eligible RCTs including a total of 13,177 patients. QFR-guided PCI was associated with reduced MACE, MI, and TLR compared with CA-guided PCI (relative risk (RR) 0.68; 95 % confidence interval (CI] [0.49 to 0.94], RR 0.58; 95 % CI [0.36 to 0.96], and RR 0.58; 95 % CI [0.38 to 0.91], respectively). There were no significant differences in any pairs for all-cause death, cardiovascular death, or stent thrombosis. QFR was ranked the best in most outcomes. In the subgroup analysis of the ACS cohort, there were no significant differences in MACE between any comparisons. CONCLUSIONS: QFR was associated with reduced MACE, MI, and TLR compared with CA, and ranked the best in most outcomes. However, this was not applied in the ACS cohort.