Ischemic Events Research Articles

Peak Ankle Arterial Duplex Ultrasound Velocities Associate With Mortality and not Ischemic Events in the Peripherally Cannulated VA-ECMO Patient

Peak Ankle Arterial Duplex Ultrasound Velocities Associate With Mortality and not Ischemic Events in the Peripherally Cannulated VA-ECMO Patient

Patent foramen ovale closure in ischemic stroke patients with and without thrombophilia: a systematic review and meta-analyses.

Ischemic stroke patients with thrombophilia and patient foramen ovale (PFO) may have an increased risk of recurrent stroke and transient ischemic attack (TIA), and may benefit from PFO closure. However, screening for thrombophilia is not routinely performed and the impact of thrombophilia on prognosis after PFO closure is uncertain. We aim to compare the risk of recurrent stroke and TIA after PFO closure in patients with thrombophilia versus those without. We performed a systematic review and meta-analyses of the literature, with a comprehensive literature search performed on 12 January 2023. Studies comparing the outcomes of patients with and without thrombophilia after PFO closure were included. The primary outcome evaluated was a recurrence of acute cerebrovascular event (ACE), a composite of recurrent ischemic stroke and recurrent TIA. The secondary outcomes included recurrent ischemic stroke only or TIA only. A total of 8 cohort studies were included, with a total of 3514 patients. There was an increased risk of stroke/TIA in patients with thrombophilia compared to those without thrombophilia after PFO (OR: 1.42, 95% CI: 1.01-1.99, I2 = 50%). The association between risk of TIA only (OR: 1.36, 95% CI: 0.77-2.41, I2 = 0%) and stroke only (OR: 1.09, 95% CI: 0.54-2.21, I2 = 0%) with thrombophilia did not reach statistical significance. There is an increased risk of recurrent cerebral ischemia event in patients with thrombophilia compared to those without thrombophilia after PFO closure. Future large prospective studies are necessary to characterise the risk and benefits of PFO closure, as well as the appropriate medical treatment to reduce the risk of recurrent stroke and TIA in this high-risk population.

Protocolized reduction of non-resuscitation fluids versus usual care in septic shock patients (REDUSE): a randomized multicentre feasibility trial

Background/purposeNon-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care.MethodsAdults with septic shock in six Swedish ICUs were randomized within 12 h of ICU admission to receive either protocolized reduction of non-resuscitation fluids or usual care. The primary outcome was the total volume of fluid administered within three days of inclusion.ResultsMedian (IQR) total volume of fluid in the first three days, was 6008 ml (interquartile range [IQR] 3960–8123) in the restrictive fluid group (n = 44), and 9765 ml (IQR 6804–12,401) in the control group (n = 48); corresponding to a Hodges–Lehmann median difference of 3560 ml [95% confidence interval 1614–5302]; p < 0.001). Outcome data on all-cause mortality, days alive and free of mechanical ventilation and acute kidney injury or ischemic events in the ICU within 90 days of inclusion were recorded in 98/98 (100%), 95/98 (98%) and 95/98 (98%) of participants respectively. Cognition and health-related quality of life at six months were recorded in 39/52 (75%) and 41/52 (79%) of surviving participants, respectively. Ninety out of 134 patients (67%) of eligible patients were randomized, and 15/98 (15%) of the participants experienced at least one protocol violation.ConclusionProtocolized reduction of non-resuscitation fluids in patients with septic shock resulted in a large decrease in fluid administration compared with usual care. A trial using this design to test if reducing non-resuscitation fluids improves outcomes is feasible.Trial registrationClinicaltrials.gov, NCT05249088, 18 February 2022. https://clinicaltrials.gov/ct2/show/NCT05249088

Deciphering smooth muscle cell heterogeneity in atherosclerotic plaques and constructing model: a multi-omics approach with focus on KLF15/IGFBP4 axis

BackgroundRuptured atherosclerotic plaques often precipitate severe ischemic events, such as stroke and myocardial infarction. Unraveling the intricate molecular mechanisms governing vascular smooth muscle cell (VSMC) behavior in plaque stabilization remains a formidable challenge.MethodsIn this study, we leveraged single-cell and transcriptomic datasets from atherosclerotic plaques retrieved from the gene expression omnibus (GEO) database. Employing a combination of single-cell population differential analysis, weighted gene co-expression network analysis (WGCNA), and transcriptome differential analysis techniques, we identified specific genes steering the transformation of VSMCs in atherosclerotic plaques. Diagnostic models were developed and validated through gene intersection, utilizing the least absolute shrinkage and selection operator (LASSO) and random forest (RF) methods. Nomograms for plaque assessment were constructed. Tissue localization and expression validation were performed on specimens from animal models, utilizing immunofluorescence co-localization, western blot, and reverse-transcription quantitative-polymerase chain reaction (RT-qPCR). Various online databases were harnessed to predict transcription factors (TFs) and their interacting compounds, with determination of the cell-specific localization of TF expression using single-cell data.ResultsFollowing rigorous quality control procedures, we obtained a total of 40,953 cells, with 6,261 representing VSMCs. The VSMC population was subsequently clustered into 5 distinct subpopulations. Analyzing inter-subpopulation cellular communication, we focused on the SMC2 and SMC5 subpopulations. Single-cell subpopulation and WGCNA analyses revealed significant module enrichments, notably in collagen-containing extracellular matrix and cell-substrate junctions. Insulin-like growth factor binding protein 4 (IGFBP4), apolipoprotein E (APOE), and cathepsin C (CTSC) were identified as potential diagnostic markers for early and advanced plaques. Notably, gene expression pattern analysis suggested that IGFBP4 might serve as a protective gene, a hypothesis validated through tissue localization and expression analysis. Finally, we predicted TFs capable of binding to IGFBP4, with Krüppel-like family 15 (KLF15) emerging as a prominent candidate showing relative specificity within smooth muscle cells. Predictions about compounds associated with affecting KLF15 expression were also made.ConclusionOur study established a plaque diagnostic and assessment model and analyzed the molecular interaction mechanisms of smooth muscle cells within plaques. Further analysis revealed that the transcription factor KLF15 may regulate the biological behaviors of smooth muscle cells through the KLF15/IGFBP4 axis, thereby influencing the stability of advanced plaques via modulation of the PI3K-AKT signaling pathway. This could potentially serve as a target for plaque stability assessment and therapy, thus driving advancements in the management and treatment of atherosclerotic plaques.

PERCUTANEOUS CLOSURE OF PATENT FORAMEN OVALE AFTER A FAILED DEVICE–CLOSURE ATTEMPT: A HIGH–VOLUME SINGLE CENTRE EXPERIENCE

Abstract Introduction Persistence of patent foramen ovale (PFO) has been associated with cryptogenic stroke due to a paradoxical systemic embolism. In these cases, a percutaneous closure allows to decrease the risk of redo cerebral ischemic events. However, the presence of a complex anatomy might prevent a correct device–deployment with a high–risk o residual shunt and/or device embolization. We describe our experience about alternative technique after a failed device closure attempt. Methods We reviewed six cases wherein the device was not able to close effectively the PFO. In these cases, alternative techniques and skills were adopted to close the PFO. Results From 2021 to 2023, 194 PFO were closed in the congenital catheterization laboratory of Monaldi Hospital (Naples). In the most of cases (188/194 pts, 96.9%) an effective device closure was obtained. However, in 6 cases (3.1%) the device failed to have a PFO closure. In these 6 patients, the PFO anatomy was characterized by: a severe hypertrophy of the septum secundum (2 cases, 33%), an aneurysmatic interatrial septum (3 cases, 50%), a long stiff tunnel (6 cases, 100%). In three cases a deviceless suture–mediated system (NoblestichTM) was effective to achieve a complete PFO closure; whereas, in two cases a combined approach (suture–mediated system followed by a device deployment) allowed to achieve a complete PFO closure. In a patient with Ebstein anomaly and significant cyanosis due to right–to–left PFO shunt, a partial PFO closure (with mild residual right–to–left shunt) was obtained after NoblestichTM deployment. In this setting, the partial PFO closure was effective to achieve a significant improvement of the patient’s arterial saturation and the procedure stopped without to complete the PFO closure with a device. Conclusion Trans–catheter device closure is often effective to achieve a complete PFO closure. However, in some circumstances, the device was unable to have an appropriate PFO closure. A suture–mediated system or a combined approach (suture–mediated system with concomitant device deployment) are effective to achieve the PFO closure in these complex scenarios.

POOR GLYCEMIC CONTROL IS ASSOCIATED WITH ELEVATED LEVELS OF CIRCULATING AMYLOID BETA 1–40 IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Abstract Background Recent evidence correlates Alzheimer‘s disease (AD) and diabetes mellitus (DM), through the involvement of reduced insulin–like growth factor (IGF–1). In acute myocardial infarction (AMI), low IGF–1 levels are correlated with a high risk of mortality and re–infarction. However, the DM–amyloid 1–40 (Aβ1–40) association in patients with coronary artery disease (CAD) remains unexplored. Aim and Methods To study Aβ1–40 concentrations based on glycaemic status, identify predictors of its levels, and assess the relationship between this peptide and IGF–1, we collected blood samples from 630 AMI patients on admission. Patients were classified into three groups based on haemoglobin A1c (HbA1c) levels: group 1 (189 patients without DM, HbA1c&amp;lt;39 mmol/mol), group 2 (270 patients with pre–DM, HbA1c 39–48 mmol/mol), and group 3 (171 patients with DM, HbA1c&amp;gt;48 mmol/mol). Results The cohort, mostly male (73.5%), had a mean age of 66.33 (11.28) years. Among them, 74.85% presented with ST–elevation myocardial infarction (STEMI), and 25.2% had a history of previous ischemic events. Median Aβ1–40 levels were 85.75 [53.85–128.67] pg/ml. Aβ1–40 positively correlated with age, tumor necrosis factor–alpha, HbA1c, HOMA–IR index, and TyG index. No significant correlation was observed between Aβ1–40 and IGF–1. Aβ1–40 levels increased from group 1 to group 3 (72.42 [48.79–109.26] pg/ml vs. 86.25 [53.4–125.54] pg/ml vs. 103.56 [61.78–46.31] pg/ml, respectively, p&amp;lt;0.001). Although not statistically significant, DM patients tended to have lower IGF–1 values compared to those without DM, while pre–DM patients had the lowest values, suggesting poorer glycaemic control (groups 1, 2, and 3: 575.3 [326.75–864.75] pg/ml vs. 519.25 [294.08–800.48] pg/ml vs. 528.3 [216.2–836.6] pg/ml). At logistic regression analysis, high levels of Aβ1–40 were predicted by older age, worse left ventricular systolic function, higher HOMA–IR index, higher levels of HbA1c, and poorer glomerular filtration rate (GFR), corrected by vitamin D. Conversely, lower levels of IGF–1 were predicted by older age, higher TyG index, higher HbA1c, low vitamin D levels, and compromised GFR. Conclusions Given the established link between Aβ1–40 and mortality in AMI patients, improved glycaemic control could reduce the levels of this peptide, counteract its pro–inflammatory properties and improve prognosis. Further investigations are needed to clarify the complex relationship between Aβ1–40 and IGF–1.

SAFETY AND EFFICACY OF A LIGHT ANTITHROMBOTIC REGIMEN AFTER LEFT ATRIAL APPENDAGE OCCLUSION: INSIGHTS FROM THE LOGIC (LEFT ATRIAL APPENDAGE OCCLUSION IN PATIENTS WITH GASTROINTESTINAL OR INTRACRANIAL BLEEDING) INTERNATIONAL MULTICENTER REGISTRY

Abstract Background Antithrombotic therapy (AT) after left atrial appendage occlusion (LAAO) in patients with non–valvular atrial fibrillation (NVAF) has the purpose of preventing device related thrombosis (DRT), avoiding embolic events; nevertheless, the correct antithrombotic regimen after LAAO is still under debate. Aims Aim of this substudy of the observational LOGIC registry was to describe the efficacy and safety of a light antithrombotic regimen, comprising single antiplatelet therapy or none, compared to a standard antithrombotic regimen, after a successful LAAO. Methods Patients with NVAF that underwent LAAO were previously included in the LOGIC registry. Patients receiving single or no AT were considered as light therapy group, while other regimen were considered as standard regimen group. Outcomes of interest were: death from any causes and cardiovascular death, ischemic stroke, transient ischemic attack and systemic embolization, any bleeding and major bleeding at 12 months. Results. Six hundred and twenty–eight patients were considered in the analysis, 31.4% received a light antithrombotic regimen. There were no differences in overall and cardiovascular mortality (5.1% Vs 6.7%, p=0.426 and 2.0% Vs 1.4%, p=0.553 respectively). Cerebrovascular stroke and transient ischemic attack were similar between the two groups (1.5% Vs 1.4%, p=0.898 and 1.5% Vs 1.3%, p=0.847). Light regimen was not associated with an increased rate of systemic embolism (1.0% Vs 0.7%, p=0.447 and HR 0.88 [95% CI: 0.34 – 2.27; p=0.79]). Conclusions An AT regimen based on single or no antithrombotic therapy after LAAO seems to be safe in patients with high–bleeding risk, without increasing cerebrovascular or peripheral ischemic events.

PREVALENCE OF ELEVATED LOW DENSITY LIPOPROTEIN CHOLESTEROL (LDL–C) LEVELS IN ADULT PATIENTS WITH COMPLEX CONGENITAL HEART DISEASE

Abstract Background Thanks to advances in both medical care and surgical techniques, survival for adult patients with congenital heart disease (ACHD) has significantly increased over recent years, with about 90% of them now reaching adulthood. However, as CHD patients grow older, their relative risk of developing coronary artery disease (CAD) increases. Elevated low–density lipoprotein cholesterol (LDL–C) levels play a pivotal role in the genesis of CAD in the general population. Limited data exist on the prevalence of hyperlipidemia in the ACHD population. Patients with complex CHD should be considered at increased risk for CAD, mainly related to to the severity of the CHD and aging. For this reason, it could be reasonable to apply targets used for patients at high risk of CAD. Our study aimed at describing the overall prevalence of elevated LDL–C levels in a contemporary cohort of adult patients with complex CHD. Materials and Methods This is a single–centre retrospective study. All adults with complex CHD who attended the outpatient clinic at our tertiary centre from January 2000 to April 2023 were included. Demographic, clinical and laboratory data were obtained in all patients from medical records and our dedicated databases. Results A total of 230 patients with complex CHD were included in the present study (mean age 35±11 years, 124 male, mean follow up of 117±80 months). One hundred forty–three (63%) of them showed biventricular physiology, whereas 86 (37%) patients showed univentricular heart physiology. Eighty patients from our cohort underwent Fontan operation. Twenty patients (9%) showed oxygen saturation at rest lower than 90%. Mean levels of LDL–C was 87±28 mg/dl, with 184 patients (78%) showing LDL–C levels ≥ 55 mg/dl. Conclusion Our study demonstrated that, despite their relatively younger age, elevated LDL–C levels are not uncommon in patients with severe CHD. ACHD patients with complex anatomy, such as patients after Fontan operation, should be considered at increased risk of ischaemic events and treated accordingly. Further research and international collaboration are therefore paramount to understand whether and if these patients should be treated with lower lipid drugs as for the general population.

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. PROSPERO (ID: CRD42023476470).

The Impact of Changing Antithrombotic Management in Patients With Atrial Fibrillation and Ischemic Cerebrovascular Events Despite Anticoagulation

Background Patients with atrial fibrillation (AF) are at increased risk of ischemic cerebrovascular events despite anticoagulants (AC). We aim to evaluate whether changing AC or adding antiplatelet therapy to anticoagulants (AP + AC) in patients with AF presenting with acute ischemic stroke (AIS) or transient ischemic attack (TIA) despite AC, decreases the risk of recurrent AIS/TIA compared to patients continued on same AC regimen. Methods Patients with AF on AC presenting with AIS or TIA at our center between 2011- 2021 were included. Data on Demographics, index event, antithrombotic therapy before and after index event, recurrent AIS/TIA, or major bleeding events (MBE) were extracted. Cox proportional hazards models were used to compare outcomes between AC unchange vs AC change, and AP + AC vs AC only groups. Results One hundred eighty-five patients were included (mean age 78.3 years; 62% males, median follow-up 9 months (IQR 1-34)). Seventeen patients (9%) had AC change, 100 (54%) received AP + AC, 39 (21%) had recurrent AIS/TIA, and 27 (15%) had MBE following index event. No difference was observed between AC unchange vs AC change and AP + AC vs AC only groups regarding recurrent AIS/TIA (HR 1.72 [.65-4.57], P = .27 and HR 1.02 [.53- 1.98], P = .95, respectively) or MBE (HR .85 [.19-3.67], P = .83 and HR 1.49 [.67-3.33)], P = .33, respectively). Fourteen vascular neurologists treated this cohort and 9(64%) implemented AC changes. Conclusion In this single center retrospective study of 185 patients with AF and AIS/TIA despite AC, changing AC or adding AP agents did not decrease the risk of ischemic cerebrovascular events.

Timing of oral anticoagulants initiation for atrial fibrillation after acute ischemic stroke: A systematic review and meta-analysis.

There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute ischemic stroke. Current international recommendations are based on expert opinions, while significant diversity among clinicians is noted in everyday practice. We conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model. Nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56-0.98; I2 = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43-0.95; I2 = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57-1.69; I2 = 21%), major bleeding (RR = 0.78; 95% CI:0.40-1.51; I2 = 0%), and mortality (RR = 0.94; 95% CI:0.61-1.45; I2 = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated. Early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation.

Polyvascular Disease: A Narrative Review of Risk Factors, Clinical Outcomes and Treatment.

Polyvascular disease has a significant global burden and is associated with increased risk of major adverse cardiac events with each additional vascular territory involved. The purpose of this review is to highlight the risk factors, associated outcomes, emerging genetic markers, and evidence for screening and treatment of polyvascular disease. Polyvascular disease is the presence of atherosclerosis in two or more vascular beds. It has a significant global burden, with a prevalence of 30-70% in patients with known atherosclerosis. Patients with polyvascular disease experience elevated rates of cardiovascular death, myocardial infarction and stroke, especially among high-risk subgroups like those with type 2 diabetes mellitus and there is a step-wise increased risk of adverse outcomes with each additional vascular territory involved. Genetic analyses demonstrate that some individuals may carry a genetic predisposition, while others exhibit higher levels of atherogenic lipoproteins and inflammatory markers. Routine screening for asymptomatic disease is not currently recommended by major cardiovascular societies unless patients are high-risk. While there are no established protocols for escalating treatment, existing guidelines advocate for lipid-lowering therapy. Additionally, recent studies have demonstrated benefit from antithrombotic agents, such as P2Y12 inhibitors and low-dose anticoagulation, but the optimal timing and dosage of these agents has not been established, and the ischemic benefit must be balanced against the increased risk of bleeding in the polyvascular population. Due to the high prevalence and risks associated with polyvascular disease, early identification and treatment intensification are crucial to reduce disease progression. Future research is needed to develop screening protocols and determine the optimal timing and dosing of therapy to prevent ischemic events.

Discharge of Acute Coronary Syndrome Patients on Sub-Optimal Dual Anti-Platelet Therapy: A Single Center Experience.

To identify and quantify the reasons why acute coronary syndrome (ACS) patients undergoing stenting at the University of New Mexico Hospital (UNMH) were prescribed sub-optimal dual antiplatelet therapy (DAPT) at discharge, and to identify practice patterns that could potentially lead to improved DAPT treatment for these patients. We reviewed electronic medical records and cardiac catheterization records of 326 patients who underwent percutaneous coronary intervention (PCI) at UNMH between January 1, 2021, and June 30, 2022 and identified 229 ACS patients who survived until discharge. Demographic and clinical characteristics relevant to P2Y12 inhibitor selection were obtained from a review of medical records. Pharmacists' notes documenting their efforts to secure appropriate insurance coverage and reasons for discharging patients on clopidogrel rather than ticagrelor/prasugrel were reviewed. Patients discharged on aspirin and clopidogrel underwent review of medical records and cardiac catheterization lab records to determine if the discharge P2Y12 drug was appropriate. Reasons for inappropriate discharge on clopidogrel were categorized as cost/insurance, patient preference, concern for daily adherence to a twice-daily medication, and maintenance of pre-hospital clopidogrel therapy rather than switch to ticagrelor after PCI. The 229 ACS patients included 87 (38.0%) appropriately discharged on ticagrelor/prasugrel, 63 (27.5%) appropriately discharged on clopidogrel, 75 (32.8%) discharged on sub-optimal clopidogrel, and 4 (1.7%) not discharged on a P2Y12 inhibitor. For patients inappropriately discharged on clopidogrel (n = 75), the most common reasons were cost or lack of insurance (n = 56) and clinical inertia (taking clopidogrel before PCI and maintained on it afterward) (n = 17). Sub-optimal P2Y12 therapy at discharge was significantly associated with lack of insurance (odds ratio 21.5, 95% confidence interval 5.33-156,p < 0.001) but not with ethnicity, age, sex, or diabetes. At the University of New Mexico, a safety-net hospital, increasing financially restricted access to ticagrelor/prasugrel could help up to 24.5% of ACS patients reduce their risk of ischemic events. For patients admitted on clopidogrel DAPT, escalating to ticagrelor/prasugrel could reduce ischemic risk in 7.4%. Expanding and improving healthcare insurance coverage might reduce the frequency of discharge on sub-optimal P2Y12 therapy.

In-hospital trimethylamine N-oxide (TMAO) variation predicts major adverse cardiovascular events in myocardial infarction survivors

Abstract Funding Acknowledgements None. Background Trimethylamine N-oxide (TMAO), a gut microbiota result of the fermentation of animal foods rich in choline, L-carnitine and phosphatidylcholine (red meat, egg yolk, dairy food), is associated with alterations in lipid metabolism, increased foam cell formation, promotion of inflammation, oxidative stress, platelet aggregation and thrombosis. To date the data evaluating TMAO as a predictor of mortality and ischemic events in patients with acute myocardial infarction (AMI) based on one-time measurement of TMAO levels lead to conflicting results. TMAO levels are fluctuating and in addition to diet, genetic factors, general condition and some co-morbidities affect its circulating levels. Purpose Since, there is a need for better risk stratification of AMI patients before the hospital discharge for more personalised treatment, we evaluated in-hospital variation in TMAO levels and its impact on outcome. Methods Blood samples from 149 consecutive AMI patients were collected on admission and on discharge. The endpoint was a three-point major adverse cardiovascular events (MACE) composed as all-cause mortality, reinfarction and development of heart failure. Results The majority of AMI patients were male (77%), hospitalized for first coronary event, with mean age 64(11) years. Median circulating TMAO level was significantly higher on admission than on discharge, (7.81 [3.47 –19.98] vs 3.45 [2.3 – 4.78] μM, respectively, p&amp;lt;0.001). In order to evaluate the impact of TMAO variation during the hospital stay on outcome, we estimated TMAO cut-off value by continuous hazard ratio analysis; values above the 3.45 μM were associated with incident of MACE in a linear fashion (Fig. 1a). Subsequently, we stratified AMI patients in 2 groups: 1) LL/HL (low-low/high-low) that included 75 (50.3%) patients whose TMAO levels remained low or were high and decreased during hospitalization and 2) HH/LH (high-high/low-high) including 74 patients (49.7%) patients whose TMAO levels remained elevated or were initially low, but rose above the estimated threshold during hospitalisation (Fig. 1b). Thirty-two (21.5%) patients reached the combined endpoint during the median follow-up of 30 months. The Kaplan-Meier analysis demonstrated that patients from the HH/LH group had a higher likelihood of experiencing MACE (p=0.05) (Fig. 2a). The multivariate Cox analysis revealed that patients in the HH/LH group had over twice the risk of MACE compared to those in the LL/HL group. Furthermore, older age and worse left ventricular systolic function were identified as independent predictors of MACE during long-term follow-up (Fig. 2b). Conclusions AMI patients with permanently elevated or increasing levels of TMAO have a worse outcome. The novelty and the strength of our study is the fact that the direction of variation of TMAO during the index hospitalisation identifies patients at higher risk of MACE during 30 months follow-up.

Incremented Amyloid-beta values predict mortality during long-term follow-up in patients with acute myocardial infarction, both STEMI and NSTEMI

Abstract Funding Acknowledgements None. Background Both the amyloid-β (Aβ) isoforms, namely Aβ1-40 and Aβ1-42 are implicated in the pathogenesis of Alzheimer’s disease through different mechanisms. While Aβ42 easily forms oligomers in brain, Aβ1-40 is more abundant in circulation where it exerts a pro-inflammatory role. Recently, Aβ1-40 has raised interest in the cardiovascular field for its contribution to atherosclerosis, more specifically through plaque formation and destabilization. However, to date, the prognostic role of Aβ1-40 in patients with acute myocardial infarction (AMI) is limited to NSTEMI. Purpose Since there is a need for better risk stratification of AMI patients, we analyzed the impact of plasma Aβ1-40 on long-term mortality in a cohort of real-world patients with AMI, including STEMI and NSTEMI. Further, we sought to identify predictors for elevated Aβ1-40 levels. Methods Blood samples were obtained from patients hospitalized for AMI and Aβ1-40 levels were evaluated with Human Aβ40 ELISA Kit. The endpoint was all-cause mortality. Results Our population included 1119 consecutive patients, with a mean age of 67 years, 72% male, 2/3 of them had a first ischemic event and 68.4% had STEMI diagnosis. The median plasma Aβ1-40 concentration on admission was 86.9 [54.5-128.9] pg/ml and there was no difference in Aβ1-40 levels between NSTEMI and STEMI (93.6 [61.2-130.9] Vs. 85.3 [52.9-128.7] pg/ml, respectively, p=0.1). At logistic regression multivariate analysis, higher Aβ1-40 levels were predicted by older age, worse left ventricular systolic function, HbA1C &amp;gt; 39 mmol/mol and GFR&amp;lt;60ml/min/m 2 (Fig.1a). From the final multivariable model, a nomogram for prediction of high levels of Aβ1-40 was computed (Fig.1b). One hundred ninety-three patients (17.2%) died, during the median follow-up of 57 [30 - 80] months. Patients who died had significantly higher levels of Aβ1-40 compared to alive patients (113.1 [67.9 – 159.5] Vs. 83.9 [52.5 – 122.6] pg/ml, p&amp;lt;0.01). Higher plasma Aβ1-40 values were associated with increased mortality risk, in both STEMI and NSTEMI (p&amp;lt;0.01) (Fig.2a). Further, at Cox multivariate analysis including the whole population, Aβ1-40 levels were predictive of mortality (HR 1.03, p=0.02), together with older age, higher Il-1β, GFR&amp;lt;60ml/min/m 2 and worse left ventricular systolic function (Fig.2b). The predictive value of our final model was superior to GRACE score for up to 60 months (AUC 0.830 (0.793 – 0.868) Vs 0.797 (0.756 – 0.837), respectively, p=0.03, Fig.2c), after which they were comparable. Conclusions Elevated levels of Aβ1-40 values are independent predictors of long-term mortality in a real-world cohort including both STEMI and NSTEMI patients.

Characteristics, management and prognosis of patients with coronary artery disease undergoing coronary intervention and atrial fibrillation

Abstract Funding Acknowledgements None. Introduction The selection of antithrombotic treatment in patients with ischaemic heart disease (IHD) and atrial fibrillation (AF) represents a challenge when trying to balance ischaemic and haemorrhagic risk. However, there is little "real-life" data on the selected antithrombotic treatment and its short and long-term prognosis. Methods A Prospective multicentre study that includes patients with IHD [acute coronary syndrome (ACS) or chronic coronary syndrome (CCS)] and AF admitted to 13 Spanish centres. The objective is to describe the characteristics, antithrombotic treatment and prognosis of patients undergoing PCI and AF. Results 373 patients were included. The average age was 77.6 ± 9.8 years (28% women). Patients had a high ischaemic and haemorrhagic risk [CHA2DS2VASc 4 (2-5) and HASBLED 3 (2-4)], with 25.5% being frail according to the Clinical Frailty Scale. The main reason for admission was ACS (44.8% NSTEMI, 22.2% STEMI and 33% CCS ), and 49.8% of patients had multivessel disease. 70.3% of patients underwent revascularisation, mainly percutaneously (92.2%). Among those percutaneously revascularised, the most used antithrombotic treatment was triple therapy with double antiplatelet therapy (DAPT) + oral anticoagulant (OAC) (62.5%), followed by double therapy with monoantiplatelet therapy + OAC (29.2%). In revascularised patients over 80, the most selected antithrombotic therapy was similar: 60.5% and 28.9%, respectively. The most used OAC was apixaban (42.3%), followed by vitamin K antagonists (17.3%). One-year survival was 88.5%. 2.6% of patients presented an ischemic stroke, and 4.8% suffered a new ACS. At the same time, haemorrhagic events (BARC ≥2) were 8.9%. Conclusions A high ischaemic and haemorrhagic risk co-exists in patients with IHD and AF. In our setting, triple therapy, mainly with the use of DOACs over VKA, is the preferred therapy. The long-term mortality of this subgroup of patients with IHD is high (&amp;gt;10%), with a rate of haemorrhagic events (8.9%) higher than ischaemic events (4.8%).Characteristics of patients

Routine Functional Testing or Standard Care in High-Risk Patients after Percutaneous Coronary Intervention.

This review aimed to collate the available evidence on outcomes following routine functional stress testing vs standard of care (i.e. symptom-guided stress testing) in high-risk patients following percutaneous coronary intervention (PCI). The most recent pragmatic POST-PCI trial provided randomized evidence showing that routine functional stress testing post-PCI did not lead to a reduction in 2-year ischemic cardiovascular events or all-cause mortality, as compared to a symptom-guided standard-of-care approach. This was also true for sub-analyses including multivessel or left main disease, diabetics, as well as following imaging or physiology guided PCI. In the absence of a change in their clinical or functional status suggestive of stent failure, post-PCI routine periodic stress testing in stable patients on guideline-directed medical therapy is currently not recommended by American clinical practice guidelines. While evidence on the cost-effectiveness of routine stress testing strategy is scarce, physician, payer, and policy-level interventions to reduce inappropriate use of routine functional testing need to be addressed.

What if youth is not enough? Acute coronary syndrome in young patients

Abstract Funding Acknowledgements None. Background Acute Coronary Syndromes (ACS) are the leading cause of mortality in Spain. Further research is needed in order to know risk factors and outcomes in young patients so that medicians could optimize their management and prevention. Purpose Identifying risk factors, clinical characteristics and short-term outcomes in Acute Coronary Syndrome in patients aged 40 and under. Methods A retrospective analysis of patients under 40 years of age who were admitted for ACS, out of 3,859 ACS admissions in Cardiology Intensive Care Unit (CICU) in our hospital between 2012 and 2022. Results 67 patients (1.73%) were included, most of them were males (83.6%). Baseline characteristics are summarized in Table 1. 77.6% had hypertension (HTA), 22.4% had diabetes (DM) and 34.3% had dyslipidemia (DLP). 79.1% were smokers, 9.1% had a history of alcoholism and 29.9% were cocaine users. None of them had a history of stroke, atrial fibrillation (AF). Only 3% had ischemic heart disease. 68.7% of them were ST-elevation myocardial infarction (STEMI) and inferior STEMI was the most common (38.7%). In anterior STEMI (22 patients), 15 had a severe lesion in the mid-left anterior descending artery (LAD), and 6 in the left main stem (LM). Single-vessel disease was the most common (70.8%), with 3-vessel disease in 4.6%. 75.8% received percutaneous coronary intervention (PCI), and 3% underwent bypass surgery. During admission, 10.5% progressed to Killip class III-IV. The ICU mortality was 1.5%. 9% received vasoactive drugs and 4.5% were intubated. Non-invasive ventilation was used in 3% and high-flow nasal cannula oxygen therapy in 5.3%. 3% received intra-aortic balloon pump support and 1.5% underwent dialysis or ultrafiltration. 4.5% received an implantable cardioverter-defibrillator (ICD), although none of them developed bundle branch block or atrioventricular node block, nor AF. After discharge, 11.1% had recurrent ACS, and up to 5.6% underwent PCI again, with a mortality rate of 11.8%. Conclusion Approximately 2% of ACS occur in people younger than 40 years of age. Substance abuse (smoking, cocaine and alcoholism) becomes more prevalent in this group. Prevalence of comorbidities (such as diabetes and nephropathy) are lower, making them less prone to short-term heart failure. However, they are more susceptible to recurrent ischemic events. There is a high incidence of inferior STEMI and LM-STEMI. For these reasons, medicians may need to find out a substance abuse in this group and further research into other risk factors, such as coronary disease family history.Basal characteristicsClinical evolution of patients

Lipid mediators in neutrophil biology: inflammation, resolution and beyond.

Acute inflammation is the body's first defense in response to pathogens or injury. Failure to efficiently resolve the inflammatory insult can severely affect tissue homeostasis, leading to chronic inflammation. Neutrophils play a pivotal role in eradicating infectious pathogens, orchestrating the initiation and resolution of acute inflammation, and maintaining physiological functions. The resolution of inflammation is a highly orchestrated biochemical process, partially modulated by a novel class of endogenous lipid mediators known as specialized pro-resolving mediators (SPMs). SPMs mediate their potent bioactions via activating specific cell-surface G protein-coupled receptors (GPCR). This review focuses on recent advances in understanding the multifaceted functions of SPMs, detailing their roles in expediting neutrophil apoptosis, promoting clearance by macrophages, regulating their excessive infiltration at inflammation sites, orchestrating bone marrow deployment, also enhances neutrophil phagocytosis and tissue repair mechanisms under both physiological and pathological conditions. We also focus on the novel role of SPMs in regulating bone marrow neutrophil functions, differentiation, and highlight open questions about SPMs' functions in neutrophil heterogeneity. SPMs play a pivotal role in mitigating excessive neutrophil infiltration and hyperactivity within pathological milieus, notably in conditions such as sepsis, cardiovascular disease, ischemic events, and cancer. This significant function highlights SPMs as promising therapeutic agents in the management of both acute and chronic inflammatory disorders.

Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction and High Bleeding Risk: A Randomized Clinical Trial.

Patients with high bleeding risk (HBR) have a poor prognosis, and it is not known if they may benefit from complete revascularization after myocardial infarction (MI). To investigate the benefit of physiology-guided complete revascularization vs a culprit-only strategy in patients with HBR, MI, and multivessel disease. This was a prespecified analysis of the Functional Assessment in Elderly MI Patients With Multivessel Disease (FIRE) randomized clinical trial data. FIRE was an investigator-initiated, open-label, multicenter trial. Patients 75 years or older with MI and multivessel disease were enrolled at 34 European centers from July 2019 through October 2021. Physiology treatment was performed either by angiography- or wire-based assessment. Patients were divided into HBR or non-HBR categories in accordance with the Academic Research Consortium HBR document. Patients were randomized to either physiology-guided complete revascularization or culprit-only strategy. The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. Secondary outcomes included a composite of cardiovascular death or MI and Bleeding Academic Research Consortium (BARC) types 3 to 5. Among 1445 patients (mean [SD] age, 81 [5] years; 917 male [63%]), 1025 (71%) met HBR criteria. Patients with HBR were at higher risk for the primary end point (hazard ratio [HR], 2.01; 95% CI, 1.47-2.76), cardiovascular death or MI (HR, 1.89; 95% CI, 1.26-2.83), and BARC types 3 to 5 (HR, 3.28; 95% CI, 1.40-7.64). The primary end point was significantly reduced with physiology-guided complete revascularization as compared with culprit-only strategy in patients with HBR (HR, 0.73; 95% CI, 0.55-0.96). No indication of interaction was noted between revascularization strategy and HBR status for primary and secondary end points. HBR status is prevalent among older patients with MI, significantly increasing the likelihood of adverse events. Physiology-guided complete revascularization emerges as an effective strategy, in comparison with culprit-only revascularization, for mitigating ischemic adverse events, including cardiovascular death and MI. ClinicalTrials.gov Identifier: NCT03772743.