bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy biomarkers in patients with acute myocardial infarction
Authors: Kong M G , Suh J , Cho Y H , Lee N H , Park H W 
Published: October 2022

Abstract

Introduction
Acute myocardial infarction (AMI) is still one of leading cause for mortality and disability in cardiovascular disease [1]. Autophagy is an intracellular mechanism involved in the elimination and the recycling of proteins and organelles by lysosomes [2]. Autophagy has an important role of critical cellular process for the self-protective degradation mechanism and recycling of cellular components in ischemic events such as AMI and left ventricular remodeling [3]. However, very few studies are evaluated the activity of autophagy and the relationship between autophagy activity and prognosis in patients with AMI.

Purpose
We aimed to evaluate the activity of autophagy in patients with AMI. Moreover, our study evaluated the associations of autophagy biomarkers with traditional cardiac biomarkers such as CK-MB, Troponin T and NT-proBNP, and echocardiographic left ventricular ejection fraction (LVEF).

Methods
We prospectively enrolled AMI patients with urgent coronary revascularization and controls who underwent coronary angiography without significant coronary artery stenosis. We obtained the serum of patients from peripheral artery and coronary artery before coronary revascularization. Levels of LC3-II, ATG5, Beclin 1 and M30 were quantified by ELISA in the serum from 22 AMI patients and 19 controls. Associations between autophagy biomarkers and traditional cardiac biomarkers were analyzed by Spearman bivariate correlation analysis.

Results
There were no significant differences in age, gender, systolic blood pressure, diastolic blood pressure, heart rate and medical history including hypertension, diabetes, dyslipidemia and atrial fibrillation between two groups. AMI patients had significant higher concentrations of autophagy biomarkers such as LC3-II (218.2±47.1 vs. 117.2±28.0 ng/ml; 238.4±60.5 vs. 118.5±27.7 ng/ml; p&lt;0.001), ATG5 (205.6±57.8 vs. 62.9±40.0 ng/ml; 199.5±56.3 vs. 68.4±54.7 ng/ml; p&lt;0.001), and Beclin 1 (225.6±55.1 vs. 123.8±16.6 ng/ml; 222.1±51.4 vs. 115.4±21.4 ng/ml; p&lt;0.001) in peripheral artery and coronary artery, both (Figure 1). M30 of apoptosis level was also significantly higher in AMI patients than in controls (262.0±78.6 vs. 148.4±57.7 ng/ml; 290.4±128.5 vs. 144.5±50.1 ng/ml; p&lt;0.001). Especially, LC3-II and Beclin 1 in coronary artery had strong positive correlations with Troponin T (rho=0.630, p&lt;0.001; rho=0.624, p&lt;0.001, respectively).

Conclusions
Autophagy biomarkers such as LC3-II, ATG5 and Beclin 1 were significantly higher in AMI patients than in controls. Autophagy biomarkers had significant positive correlations with Troponin T and NT-proBNP as the traditional cardiac biomarkers and negative correlations with LVEF.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)
Direct oral anticoagulants compared to vitamin K-antagonists in patients with left ventricular thrombus
Authors: Seiler T , Vasiliauskaite E , Cioffi G M , Madanchi M , Attinger A , Staempfli S F , De Boeck B , Kobza R , Toggweiler S , Moccetti F , Wolfrum M , Suter Y , Grueter D , Cuculi F , Bossard M 
Published: October 2022

Abstract

Background/Introduction
In the setting of left ventricular thrombus (LVT), direct oral anticoagulants (DAOC) are poorly studied. Current European guidelines recommend treatment with Vitamin K antagonists (VKA) for 6 months. So far, several observational studies reported similar efficacity and safety of DOACs, compared to VKAs. Controversial findings were found in one big cohort, where higher stroke rates were reported among patients treated with DOAC compared to VKA, what raised concerns about the efficiency and safety to use DOACS in the setting of LVT.

Purpose
This retrospective multicenter study compared thrombus resolution and clinical outcomes of patients with LVT treated with DOACs or VKAs.

Methods
From an echocardiography database of three teaching hospitals in Switzerland, patients diagnosed with LVT between 2015 and 2021 were identified. All echocardiograms and outcomes were reviewed by independent physicians. Thrombus resolution rate and clinical outcomes were compared according to the underlying anticoagulation regimen.

Results
Overall, 101 patients (17.8% females, mean age 63.3±13.2 years) were included. Among those, 50.5% had a recent myocardial infarction, 38.6% chronic ischemic heart disease and 10.9% suffered from non-ischemic cardiomyopathy. At hospital discharge, 48 (47.5%) were treated with DOACs and 53 (52.5%) with VKAs. Initial left ventricular ejection fraction was 38±13%. 93.1% patients presented with apical wall motion abnormalities, mean wall motion score index was 1.91±0.39. Initial thrombus size was comparable in both groups (table 1).
Median follow-up was 799 (354; 1236) days and the clinical composite endpoint combining stroke, systemic embolism, bleedings, myocardial infarction and death was comparable in the VKA (22.6%) and DOAC (27.1%) group, respectively. There was no difference in major (4% vs. 6.3%) and minor (13.5% vs. 4.3%) bleeding events, neither for stroke and systemic thromboembolism (14.3% vs 14.9%) or death (11.3% vs 8.5%). Thrombus resolution rate after 1 year was similar in the VKA and DOAC group (75.5% vs. 76.7%), but early thrombus dissolution within the first month was faster in the VKA arm (p=0.049). In each group, 3 subjects had thrombus recurrence after cessation of anticoagulation.

Conclusion
Among patients with LVT, DOACs appear to be a safe and effective alternative to vitamin K antagonists, but thrombus seems to dissolve slower in the first month. An adequately powered randomized trial is needed to confirm these findings.

Funding Acknowledgement
Type of funding sources: None.
Platelet extracellular vesicles are superior to cardiac troponin to diagnose acute coronary syndrome with short symptom duration: LEMONADE trial
Authors: Gasecka A , Budzianowski J , Wawiorka M , Palucha K , Pieszko K , Hiczkiewicz J , Filipiak K J , Grabowski M , Falkema K , Van Der Pol E , Nieuwland R 
Published: October 2022

Abstract

Background
Acute coronary syndrome (ACS), which comprises acute myocardial infarction (AMI) and unstable angina pectoris (UAP), is one of the main causes of mortality worldwide. Cardiac troponin is the gold standard to diagnose AMI. Troponin has two main disadvantages: it is negative in patients with UAP but positive in other diseases. During ACS, activated platelets release extracellular vesicles (EVs), which promote coagulation and associate with fibrin, and contribute to thrombus formation. We hypothesized that the concentration and composition of circulating platelet EVs (1) change in blood of patients with ACS compared to patients with other causes of chest pain, and (2) thereby allow earlier diagnosis of ACS than cardiac troponin.

Purpose
We aimed to determine the diagnostic value of circulating platelet EVs as novel early biomarkers of developing ACS.

Methods
We conducted a prospective, multicentre trial enrolling 105 patients who presented to the emergency department with suspected ACS. Blood was collected at admission to measure the concentration of EVs and cardiac troponin. Flow cytometry (Apogee A60-Micro) was used to determine plasma concentrations of platelet EVs exposing P-selectin (CD61+/CD62p+) and fibrin (CD61+/fibrin+).

Results
Plasma concentrations of platelet EVs exposing fibrin was lower in patients with ACS, compared to patients with other causes of chest pain (p=0.023) and lower in patients with an occlusive thrombus compared to non-occlusive plaque (p=0.015). Fibrin exposing-EVs were independent predictors of ACS (OR 8.2, CI 1.3–16.4) in multivariate analysis, allowing to diagnose ACS with 75% sensitivity and 72% specificity. Among patients with pain onset less than 2 hours before presentation, fibrin-exposing EVs had substantially better diagnostic performance than troponin (area under the ROC curve 0.90 vs. 0.74, respectively). Regarding other causes of chest pain, fibrin-exposing EVs were the lowest in patients with ACS, higher in patients with other cardiological causes of chest pain, and the highest in patients with non-cardiological causes of chest pain (p=0.036).

Conclusions
Circulating fibrin-exposing EVs are early biomarkers of developing ACS, superior to cardiac troponin in patients with pain onset less than 2 hours before presentation. Incorporation of EV measurements into the ACS diagnostic algorithm might revolutionise thrombotic risk stratification in the emergency setting.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Specialised Research Fellowship, “Club 30” of the Polish Society of Cardiology
Post-myocardial infarction late diastolic left ventricular blood flow energetics are independently associated with left ventricular remodeling
Authors: Demirkiran A , Van Der Geest R J , Hopman L H G A , Robbers L F H J , Handoko M L , Nijveldt R , Greenwood J P , Plein S , Garg P 
Published: October 2022

Abstract

Background
Post-myocardial infarction (MI) left ventricular (LV) remodeling emerges as a compensatory mechanism and leads to complex pathophysiological changes in LV blood flow hemodynamics. The interplay, if any, between LV blood flow energetics and remodeling remains unknown. We hypothesized that LV blood flow energetics early after MI are independently related to the temporal changes in LV end-diastolic volume (LVEDV).

Methods
In this prospective cohort study, 69 patients with acute re-perfused ST-segment elevation MI (STEMI) were included. The patients underwent cardiovascular magnetic resonance (CMR) examination within 2 days of the index event and at 3-month. CMR examination included cine, late gadolinium enhancement, and whole-heart 4D flow acquisitions. LV volume-function, infarct size (indexed to body surface area), microvascular obstruction (MVO), mitral inflow, and 4D blood flow kinetic energy (KE) characteristics were obtained. LV mean and peak KEi (indexed to LVEDV) were quantified for all time parameters (entire cardiac cycle, during systole/diastole, at E- and A-waves).

Results
In univariable linear regression analysis, peak KEi (R-R interval), mean systolic KEi, A-wave KEi, MVO presence were all associated with the relative change (%) of LVEDV (p=0.03, p=0.01, p&lt;0.01, P=0.03, respectively). In multivariable linear regression analysis, A-wave KEi was identified as the only independent marker for association with the relative change of LVEDV (p=0.02). In another univariable linear regression analysis, A-wave KEi, infarct size, and MVO presence were all associated with the absolute change of LVEDV (p=0.03, p=0.04, p=0.04, respectively). In multivariable linear regression analysis, A-wave KEi was determined as the only independent marker for association with the absolute change of LVEDV (p=0.02). No significant association was observed between mitral inflow characteristics and relative and absolute change of LVEDV.

Conclusion
Late diastolic LV blood flow energetics early after acute MI are independently associated with both absolute and relative longitudinal changes in LVEDV and may provide incremental value over infarct and mitral inflow characteristics to be associated with post-MI LV remodeling.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): British Heart Foundation
Association of ischemic and bleeding events with mortality in patients with a recent acute myocardial infarction
Authors: Simonsson M , Alfredsson J , Szummer K , Jernberg T , Ueda P 
Published: October 2022

Abstract

Background/Introduction
Duration and intensity of antithrombotic treatment after myocardial infarction should be individualized based on a patient's ischemic and bleeding risk [1,2]. While such strategies are typically based on calculations that give equal weight to both types of events, uncertainty remains regarding their relative importance.

Purpose
To describe the incidence of ischemic and bleeding events in patients with a recent myocardial infarction, to compare the association of an ischemic vs bleeding event with mortality and to assess whether this association had changed over the past two decades.

Methods
Patients with acute myocardial infarction enrolled in the SWEDEHEART registry and discharged alive with antithrombotic treatment (aspirin, P2Y12 inhibitor, or oral anticoagulant) from January 2012 to December 2017 were followed from discharge until an ischemic event (recurrent myocardial infarction or ischemic stroke) or bleeding event. Cox regression adjusted for demographic factors, comedications and comorbidities, was used to estimate hazard ratios (HR) for time to death after an ischemic and bleeding event as compared with no event (in a model using time-varying exposure definition) and for an ischemic vs bleeding event in a direct comparison. We then assessed whether the adjusted HR for mortality of an ischemic vs bleeding event had changed across three time-periods (1997–2000, 2001–2011 and 2012–2017) by using an interaction term between time period and type of event.

Results
From January 2012 until December 2017 86, 736 patients were discharged alive with antithrombotic treatment after a myocardial infarction. Of these, 4,039 patients experienced a first ischemic event (incidence rate 5.7 events per 100 person-years), and 3,399 a first bleeding event (incidence rate 4.8 events per 100 person-years). As compared with no event, both ischemic events (adjusted HR 4.16, 95% CI 3.91 to 4.43) and bleeding events (adjusted HR 3.43, 95% CI 3.17 to 3.71) were associated with an increased risk of death. In the direct comparison, ischemic events were associated with a higher risk of death than bleeding events (adjusted HR 1.27, 95% CI 1.15 to 1.40). There was no evidence of a change in the aHR across the three time periods (aHR; 1.17, 95% CI 1.02 to 1.35 in 1997–2000 and 1.18, 95% CI, 1.11 to 1.27 in 2001–2011, p for interaction between time period and type of event ≥0.646).

Conclusion
In this nationwide study of patients with a recent MI, post-discharge ischemic events were more common and associated with higher mortality risk as compared with bleeding events.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Swedish Heart and Lung FoundationSwedish Diabetes Foundation
Temporal trends in the management and outcome of obese patients with an acute coronary syndrome – the ACSIS registry 2000–2018
Authors: Gurevitz C , Mohsen J , Ovdat T , Zwas D R , Fluk Gmach S , Beigel R , Eisen A 
Published: October 2022

Abstract

Introduction
Obesity has been increasing in epidemic proportions over many decades, and is clearly associated with major cardiovascular (CV) risk factors [1–2]. We aimed to examine temporal trends in the management and clinical outcomes of obese patients with an acute coronary syndrome (ACS).

Methods
Data from the ACSIS registry including all obese patients (calculated BMI of 30 or above) between the years 2000–2018. Patients were stratified by BMI to obesity classes: Class 1 – BMI 30–34; class 2 – BMI 35–39 and class 3 – BMI 40 and above. Clinical endpoints included 30d MACE and 1-year mortality. Temporal trends were examined in the late (2010–2018) vs. the early period (2000–2008).

Results
Among the 13,816 patients from the ACSIS registry with available BMI data, of whom 3567 were defined as obese, 2670 were in obesity class 1, 679 were in class 2, and 218 were defined as class 3. Patients in higher obesity classes had more CV risk-factors including dyslipidemia, hypertension, and diabetes mellitus (p&lt;0.01 for all interactions). Overall, invasive and pharmacological treatment has improved during time in all obesity classes. The rates of 30-day MACE were numerically higher among patients in class 3 (11.6% in class 1, 11.3% in class 2, and 15.6% in class 3, p-trend= 0.3), and so was the rate of 1-year mortality (7.3%, 7.3%, and 10.9%, respectively, p-trend = 0.1) Comparing the 2 time-periods, 30-day MACE was significantly lower in the late period in class 1 and 2, but has remained unchanged in class 3. Similarly, 1-year mortality has not changed during the years among patients in class 3, but has decreased among patients in classes 1 and 2 (8.6% to 5.8%, p=0.007, and 9.3% to 5.5%, p=0.08, respectively) [Figure 1].

Conclusions
In obese patients admitted with an ACS, the rates of 30-day MACE and 1-year mortality are numerically higher among patients who are extremely obese. During 2 decades, 30-day MACE and 1-year mortality have decreased among obesity classes 1 and 2, but remained unchanged among patients in class 3. Extremely obese patients admitted with an ACS are a particularly high-risk group and future efforts should examine treatment modalities in order to curtail this increased risk.

Funding Acknowledgement
Type of funding sources: None.
Added value of left atrial strain in outcome prediction after myocardial infarction. SWEDEHEART-registry based echocardiographic study
Authors: Sjolen L , Lenell J , Lindahl B , Baron T 
Published: October 2022

Abstract

Background
Left ventricular function parameters, such as ejection fraction and global longitudinal strain are widely accepted prognostic parameters after myocardial infarction. Left atrial strain has been suggested as a novel risk parameter in this population.

Objective
To investigate whether left atrial (LA) deformation parameters (LA reservoir strain, LARS) can improve prognostic value of traditional echo parameters in prediction of heart failure and dead in patients after myocardial infarction. Moreover, to study relationship between LARS and established LV function parameters, and test its reproducibility between the readers.

Method
A total of 380 patients with myocardial infarction, hospitalized at our university hospital between 2008–2014, underwent echocardiography during hospital stay. The collected images was reanalyzed with respect to left atrial strain. Patients were followed up within the Swedish myocardial infarction registry (SWEDEHEART).

Results
To the final analysis a total of 253 patients (64 years of age, 81% men) were included, and followed up over median of 4.9 years. Among the parameters tested in the univariate analysis, LARS was able to predict long-term risk of heart failure admissions and death in patients with myocardial infarction (HR 0.95, 95% CI 0.91–0.99 for combined end-point). LARS below 27.2% identifies patients with higher risk of combined endpoint with AUC 0.68 (p=0.001). After adjustment for background characteristics and established LV function measures, LARS has lost significance, meaning that it provides no additional information in this population. LARS correlates moderately with LV GLS (r=−0.52, p&lt;0.001) and weakly with LVEF (r=0.31, p&lt;0.001), to a moderate extent and to a small extent with LAVI and LVEF, respectively. LARS shows moderate to perfect agreement between reviewers.

Conclusions
LARS is a good prognosticator of death and heart failure hospitalizations after myocardial infarction, but not independent of the established LV function parameters. We showed a good correlation between LARS and LV strain parameters and its near perfect inter-reader reproducibility.

Funding Acknowledgement
Type of funding sources: None.
Cardiovascular or renal disease (CVRD) complication and mortality incidence for type 2 diabetics with a single or without CVRD comorbidity: a 5-year SNDS nationwide claims database cohort study
Authors: Jourdain P , Blin P , Zaoui P , Guiard E , Sakr D , Dureau-Pournin C , Bernard M A , Lassalle R , Thomas-Delecourt F , Bineau S , Moore N , Droz-Perroteau C , Joubert M A 
Published: October 2022

Abstract

Background
Myocardial infarction (MI), stroke, peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD) are common cardiovascular renal disease (CVRD) complications for type 2 diabetes (T2D). However, for those with a single CVRD comorbidity, the incidence of a new CVRD complication and death is not well known.

Purpose
To assess the 5-year CVRD complication and mortality incidence for T2D patients with a single CVRD comorbidity or without CVRD at baseline.

Methods
A cohort study of all T2D patients with a single CVRD or without CVRD (disease-free) at baseline (January 1st, 2014) identified and followed-up for 5 years within the French SNDS nationwide claims database. Incidence rates were estimated for 5 years and the risk of all-cause death was compared to the disease-free population using Cox proportional hazards risk model: hazard ratio (HR) with [95% confidence interval].

Results
From about 2 million T2D patients without cancer or transplantation at baseline, 76.5% were disease-free, 7.9% with a single CVRD and the others having several CVRD comorbidities history. Five-year CVRD complication and mortality incidence rates for 1,000 patient-years are presented in the table. CKD and HF were the most frequent CVRD complications for the disease-free and all CVRD comorbid populations, far ahead of MI, stroke and PAD, except PAD complication for PAD population and to a lesser degree stroke complication for stroke population. The incidence rate of all-cause death was the highest for HF+CKD patients, followed by HF patients, then PAD, stroke and CKD patients. Compared to disease-free patients with same sex and age, the HR of death was 4.3 [4.2–4.5] higher for HF+CKD patients, 2.7 [2.7–2.8], 2.1 [2.0–2.1], 2.1 [2.0–2.1], 1.9 [1.9–1.9] and 1.4 [1.3–1.4] for HF, CKD, PAD, stroke and MI patients, respectively.

Conclusions
While MI, stroke and PAD comorbidities remain major risks of complications for T2D patients, HF and CKD nowadays represent a clearly higher risk of CVRD complications and death, that needs improved preventive strategies.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Study performed with unconditional funding from AstraZeneca