bluuebunny/crossref_metadata_2025_split huggingface dataset:
Derivation and validation of a novel 3hour-pathway for the observe-zone of the ESC 0/1h-hs-cTnI algorithm
Authors: Lopez Ayala P , Boeddinghaus J , Nestelberger T , Strebel I , Koechlin L , Rubini Gimenez M , Miro O , Martin-Sanchez F J , Keller D , Mueller C 
Published: November 2023

Abstract

Background
The latest non-ST elevation myocardial infarction (NSTEMI) guidelines from the European Society of Cardiology (ESC) recommend a 3-hour cardiac troponin determination in patients triaged to the observe-zone of the ESC 0/1h-hs-cTnI algorithm; however, no specific cut-off for further triage is endorsed.

Purpose
To derive and internally validate a novel 3h-pathway for the observe-zone of the ESC 0/1h-hs-cTnI (Architect) algorithm.

Methods
In an multicentre international diagnostic study, we prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of MI. Final diagnoses were centrally adjudicated by two independent cardiologists applying the 4th universal definition of MI, based on complete cardiac work-up including cardiac imaging, serial hs-cTnI sampling and 90-day follow-up information. High sensitivity-cTnI (Architect) concentrations were measured at presentation and after 1 and 3 hours. The primary outcome was safety, quantified by the sensitivity and NPV for early rule out of NSTEMI. Internal validation was assessed with a bootstrapping procedure.

Results
Among 2481 eligible patients, application of the ESC 0/1h-algorithm triaged 1725 patients (69.5%) to either rule-out or rule-in of NSTEMI, remaining 756 patients (30.5%) in the observe-zone (adjudicated NSTEMI prevalence 65/756 patients, 13.7%). A novel derived 3h-pathway for the observe-zone patients ruled-out NSTEMI with a 3h hs-cTnI concentration &lt;8 ng/L and a 0/3h-hs-cTnI absolute change &lt;3 ng/L, triaging 241 patients (32%) towards rule-out, resulting in a sensitivity of 100% (95%CI 94.4-100) and a NPV of 100% (95%CI 98.4-100). A 0/3h-hs-cTnI absolute change ≥8 ng/L ruled-in 69 patients (9.1%), resulting in a specificity of 95.8% (95%CI 94.0-97.1) and a PPV of 58.0% (95%CI 46.2-68.9), Figure. The novel 3h-pathway reduced the number of patients remaining in the observe zone from 756 (30.5%) to 446 (18%), resulting in a relative reduction of 41%, while the number of NSTEMI was reduced from 65 to 25, resulting in a relative reduction of 62%. Findings were confirmed in the optimism-corrected bootstrap internal validation.

Conclusions
A novel derived pathway combining a 3h hs-cTnI concentration &lt;8 ng/L and a 0/3h absolute change &lt;3 ng/L allowed to safely rule-out NSTEMI in patients remaining in the observe-zone of the ESC 0/1h-hs-cTnI (Architect) algorithm.Performance of the novel derived cutoffs
Derivation and external validation of machine-learning- models for risk stratification in chest pain with normal troponin
Authors: Fernandez Cisnal A , Lopez-Ayala P , Minana G , Valero E , Koechlin L , Catarrala A , Boeddinghaus J , Noceda J , Nestelberger T , Miro Andreu O , Nunez J , Mueller C , Sanchis J 
Published: November 2023

Abstract

Importance
Risk stratification of patients with chest pain and a high-sensitivity cardiac troponin T (hs-cTnT) concentration 180 minutes). Probability thresholds for safe discharge were derived in the derivation cohort.

Methods
This prognosis study used a single centre cohort (July 2016-Decembre 2019) to develop and internally validate the models and a international prospective APACE cohort to perform the external validation. All Patients presenting to the ED with a complaint of chest pain and a first hs-cTnT concentration &lt;99th percentile (14 ng/L).Candidate predictors included demographics, tradicional cardiovascular risks factors, electrocardiogram and blood tests (haemoglobin, creatinine and hs-cTnT). The endpoint was90-days death or myocardial infarction Four machine learning-based models and one logistic regression (LR) model were trained on 4075 patients and externally validated on 3609 patients. Models were compared with GRACE and HEART scores and a single undetectable hs-cTnT-based strategy (u-cTn; hs-cTnT&lt;5ng/L and time from symptoms onset&gt;180 minutes). Probability thresholds for safe discharge were derived in the derivation cohort.

Results
A 99.1% (4074) of the patients completed the follow-up in the derivation cohort and a 99.4% (3609) in the validation cohort.The endpoint occurred in 105 (2.6%) patients in the training set and 98 (2.7%) in the external validation set. Gradient boosting full (GBf) showed the best discrimination (AUC=0.808). Calibration was good for the reduced NNET and LR models. GBf identified the highest proportion of patients for safe discharge (36.7% vs 23.4% vs 27.2%; GBf vs LR vs u-cTn, respectively) with similar safety (missed endpoint per 1000 patients: 2.2 vs. 3.5 vs. 3.1, respectively). All derived models were superior to the HEART and GRACE scores (p&lt;0.001).

Conclusions and relevance
Machine learning and logistic regression prediction models were superior to the HEART, GRACE and u-cTn for risk stratification of patients with chest pain and a baseline hs-cTnT.
Diagnostic performance of the 0/2 hours ESC algorithm with high-sensitivity cardiac troponin T in an unselected community United States cohort
Authors: De Michieli L , Ola O , Akula A , Knott J D , Mehta R A , Hodge D O , Tak T , Cagin C , Gulati R , Jaffe A S , Sandoval Y 
Published: November 2023

Abstract

Background
There are no robust data addressing the United States (US) experience with the 0/2 hours (h) European Society of Cardiology (ESC) algorithm using high-sensitivity cardiac troponin T (hs-cTnT).

Purpose
To evaluate the diagnostic performance of the 0/2h ESC-recommended absolute deltas in a US population.

Methods
Observational US cohort study of ED patients undergoing 0 and 2 h hs-cTnT measurements. The 99th percentiles upper reference limits (URL) used were 10 ng/L for women and 15 ng/L for men. Diagnostic outcomes were the adjudicated diagnoses of acute myocardial infarction (MI, type 1 or 2).

Results
A total of 1084 patients met inclusion criteria, amongst which 49% were women. Chest discomfort was reported in 521 (48%) patients. Among patients with a baseline hs-cTnT≤99th URL (n=434), 4 MIs occurred. To rule-out MI, an absolute 0-2h delta change &lt;4 ng/L resulted in a sensitivity of 100% (95% CI: 39.8, 100) and a negative predictive value (NPV) of 100% (95% CI: 99.1, 100). To rule-in MI, an absolute 0-2h delta ≥10 ng/L had a specificity of 99.8 % (95% CI: 98.7, 99.9) and positive predictive value (PPV) of 75% (95% CI: 19.4, 99.4). Among patients with a baseline hs-cTnT &gt;99th URL (n=650), 110 MIs occurred. In these patients, both rule-out (sensitivity 65%, NPV 91%) and rule-in (specificity 7.2%, PPV 11%) were poor using the ESC-recommended absolute deltas. Among patients with modest hs-cTnT increases (99th URL to 100 ng/L) neither the ESC-recommended absolute nor the Fourth Universal Definition of MI (UDMI)-recommended relative deltas provided acceptable performance. Among patients with marked hs-cTnT increases at presentation (&gt;100 ng/L), a relative delta change &gt;20% as recommended by the UDMI resulted in a superior rule-in performance, with a specificity of 92.0% (95% CI 74.0, 99.0) and PPV of 84.6% (57.4, 95.7).

Conclusions
In our unselected US-cohort of patients undergoing hs-cTnT, the 0/2h ESC algorithm had a good diagnostic performance in patients without myocardial injury at presentation. Conversely, in patients with myocardial injury at baseline, the ESC-recommended absolute deltas performed poorly to determine who had MI. In patients with marked hs-cTnT increases &gt;100 ng/L at presentation, the UDMI recommended 20% relative change showed good rule-in performance.
Invasive coronary function testing in patients with INOCA - a single center experience
Authors: Ferreira A , Teixeira R , Ferreira V , Mendonca T , Silva T P , Rodrigues H , Silva F , Marques F , Oliveira E , Ferreira R C , Ramos R 
Published: November 2023

Abstract

Background
Coronary vasomotion disorders (CVDs) represent a frequent cause of angina in patients with ischemia with non-obstructed coronary arteries (INOCA). Invasive coronary angiography (ICA) often fails to identify patients with vasospastic angina and/or microvascular dysfunction.

Purpose
Our aim was to describe and characterize CVDs in INOCA patients, using a multi-parametric, invasive, coronary function testing protocol.

Methods
Patients with INOCA that underwent our protocol for coronary function testing (CFT), between July 2021 and October 2022 were included in this single-center prospective study. The protocol consisted of an invasive assessment of coronary circulation vasorelaxation at rest and during hyperemia, as well as the propensity for coronary vasospasm using increasing doses of intra-coronary acetylcholine. Fractional flow reserve, coronary flow reserve (CFR), and index of microvascular resistance (IMR) were recorded. CVDs were diagnosed based on the criteria proposed by the Coronary Vasomotor Disorders International Study Group.

Results
A total of 56 patients were included, mean age was 64±12 years and 57.1% were female. At baseline, all patients had either typical angina (82.1%, n=46) or a positive ischemia test (67.9%, n=38). Twenty patients (35.7%) had a history of a previous ICA or computed tomography due to anginal symptoms, while only 8.9% of patients had known structural ischemic heart disease and were subjected to percutaneous coronary intervention. Our CFT protocol was completed in all patients without any serious complications. Isolated epicardial vasospasm was found in 16 (28.6%) patients, isolated coronary microvascular dysfunction (CMD) in 9 (16.1%), and a combination of CMD and coronary vasospasm in 9 (16.1%). Only 1 patient (1.8%) had isolated microvascular spasm.
We were able to further identify two distinct endotypes of CMD, using a combined assessment of CFR and IMR, termed structural and functional CMD: Functional CMD - 7 patients (12.5%) had CFR &lt; 2.0 and IMR &lt; 25; Structural CMD - 6 patients (10.7%) had CFR &lt; 2.0 and IMR &gt; 25.

Conclusion
Coronary vasomotion disorders are a common cause of INOCA. A CFT protocol is safe, can be used in clinical practice, and can provide a definite diagnosis for the underlying cause of angina.
CAD-RADS score, vascular inflammation, and plaque vulnerability
Authors: Kinoshita D , Suzuki K , Minami Y , Yuki H , Niida T , Dey D , Lee H , Mcnulty I , Ako J , Ferencik M , Kakuta T , Jang I K 
Published: November 2023

Abstract

Background
Coronary artery disease reporting and data system (CAD-RADS), which is widely used to report the severity of coronary artery disease on coronary computed tomography angiography (CTA), predicts the risk of future cardiovascular events. However, the relationship between the CAD-RADS score and vascular inflammation and plaque vulnerability has not been investigated.

Objective
The aim of this study was to correlate the CAD-RADS score with vascular inflammation and plaque vulnerability.

Methods
This is an observational, single-center cohort study with prospective clinical follow-up. Patients who underwent both coronary CTA and optical coherence tomography (OCT) before coronary intervention were enrolled. All OCT and CTA images were analyzed at the core laboratory. Patients were categorized into two groups according to the CAD-RADS score (≤4a or 4b/5). All coronary arteries were analyzed for high-risk plaque features (positive remodeling, low-attenuation plaque, napkin-ring sign, and spotty calcification) and peri-coronary adipose tissue (PCAT) attenuation. PCAT attenuation was measured around the culprit lesion and in the proximal segment of all 3 coronary arteries. OCT features of plaque vulnerability were evaluated in culprit vessels. Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as composite endpoints of unplanned target vessel revascularization, unplanned non-target vessel revascularization, nonfatal acute coronary syndrome, stroke, and cardiac death.

Results
Among 369 patients with 902 lesions, 104 (28.2%) were categorized in CAD-RADS 4b/5 and 265 (61.8%) in CAD-RADS ≤4a. Patients with CAD-RADS 4b/5 had higher PCAT attenuation than those with CAD-RADS ≤4a at all three levels (mean of 3 coronary vessels: -67.9 ± 6.9 HU vs. -70.2 ± 6.5, P=0.004; culprit vessel: -67.4 ± 7.9 vs. -70.2 ± 7.6, P=0.004; culprit plaque: -67.0 ± 9.3 vs. -69.9 ± 10.5, P=0.009; respectively) (Figure 1 A). Lipid-rich plaque and macrophage, as detected by OCT, were more prevalent in the culprit vessel in patients with CAD-RADS 4b/5 than in those with CAD-RADS ≤4a (89.0% vs. 78.5%, P=0.001; 76.6% vs. 64.9%, P=0.001; respectively) (Figure 1B). All HRP features, as detected by CTA, were more frequently observed in patients with CAD-RADS 4b/5 than those with CAD-RADS ≤4a (P for all &lt;0.001) (Figure 2). The cumulative incidence of MACCE was higher in patients with CAD-RADS 4b/5 than in those with CAD-RADS ≤4a (15.0% vs. 5.8%, P=0.045).

Conclusions
Higher CAD-RADS score was associated with a higher level of pan-coronary vascular inflammation and plaque vulnerability.Figure 1Figure 2
SGLT2 inhibitor for secondary prevention in acute myocardial infarction patients with diabetes mellitus
Authors: Kim D B , Kim H Y 
Published: November 2023

Abstract

Background
SGLT2i is effectively used for heart failure (HF), but secondary prevention after acute myocardial infarction (AMI) is unknown.

Methods
Among the National Health Insurance Service data, AMI patients hospitalized with first-use diabetes drugs were enrolled. Primary endpoints는 composite of all death and rehospitalization of HG. Secondary endpoints는 all death, rehospitalization of HF, recurrent AMI, and Ischemic stroke.

Results
We enrolled 4,831 patients (SGLT2 inhibitor: 1,739, other glucose-lowering medication: 3,092). After inverse probability of treatment weighting, primary endpoint showed a significantly good clinical outcome in SGLT inhibitor groups compared to other glucose-lowering medications. (HR, 95% CI: 0.663(0.54-0.82)). All death and HF also showed good results in SGLT2i group (0.79(0.71-0.0.91); 0.77 (0.62-0.95), respectively). There were no differences in recurrent AMI and stroke in both groups.

Conclusion
In AMI patients with diabetes, SGLT2i use is associated with a lower rate of overall death and HF, but the incidence of recurrent AMI and ischemic stroke showed no difference. These studies need to be verified as large-scale random studies in the future.
Real-world assessment of antiplatelet treatment therapies for acute coronary syndrome (ACS) patients in the United States in a nationwide Electronic Health Record in 2018-2020
Authors: Kang A , Jiang J , Li X , Horrow J , Garcia Sanchez R , O-Brien E , Abdul Sultan A , Krishnamurthy S P , Cannon C P 
Published: November 2023

Abstract

Background
Acute coronary syndrome (ACS) is one of the leading causes of cardiovascular related deaths for adults in US. The clinical presentation of ACS is broad, which includes ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation MI (NSTEMI), and unstable angina (UA). There are limited data around contemporary real-world treatment landscape, therefore it is critical to understand the treatment pattern of the US ACS patients in the real-world setting.

Purpose
This study evaluated antiplatelet therapy (APT) treatment patterns among US patients without atrial fibrillation or oral anticoagulants (OACs) who experienced their first hospitalized ACS event during observation period.

Methods
The Optum® de-identified Electronic Health Record dataset from January 2018 through December 2020 was used for this study. Adult patients with an inpatient primary diagnosis of ACS during the index period were identified by ICD10 codes. The date of admission for the first ACS hospitalization was the index date. Patients with atrial fibrillation diagnosis or a record for OAC use before index date and during hospitalization were excluded. ACS subgroups and percutaneous coronary intervention (PCI) status were assessed during index hospitalization; patient characteristics and in-hospital antiplatelet treatment type were also evaluated.

Results
Among 63,767 patients included in this study, the mean age was 64.1 and 40.5% were female; 89.2% were treated with APT. For those patients not treated with APT, majority were treated with parental anticoagulants. Among 89.2% APT treated patients, 52.7% were initiated on dual antiplatelet therapy (DAPT), 27.4% were initiated on single antiplatelet therapy (SAPT), and 9.1% switched between different DAPT regimens. The top three used DAPT were aspirin+clopidogrel (30.5%), aspirin+ticagrelor (18.9%) and aspirin+prasugrel (2.6%); the most used SAPT were aspirin (22.6%), clopidogrel (2.6%), and ticagrelor (2.0%). For ACS subtypes, 26.3% were diagnosed as STEMI, 62.9% were NSTEMI, and 10.8% were UA; of them, 45.0% had PCI procedure within 30-days before or after the index date. ACS patients with PCI procedure had the highest APT treatment rate (95.2%) and highest DAPT treatment rate (70.6%). Across ACS subtypes, patients hospitalized for STEMI had the highest usage of aspirin+ticagrelor (34.5%), whereas patients hospitalized for NSTEMI had the highest usage of aspirin+clopidogrel (34.7%).

Conclusion
We observed wide variability in APT treatment across STEMI vs. NSTEMI and +/-PCI. Only 38.1% of non-PCI treated ACS patients received DAPT despite current guidelines. Further analyses are planned to explore the varying APT (and/or anticoagulant) regimens.Figure 1Figure 2
Early initiation of PCSK9 inhibitor therapy versus placebo in patients with acute coronary syndrome: a systematic review and meta-analysis
Authors: Justino G B , Justino L B , Muller M E , Rocha A V , Mazetto A , Cardoso R , Leucker T M 
Published: November 2023

Abstract

Background
In patients with stable atherosclerotic cardiovascular disease (ASCVD) and prior atherosclerotic events, PCSK9 inhibitors (PCSK9i) have shown a 50-60% reduction in LDL-C from baseline, on a background of high-intensity or maximally tolerated statin therapy, leading to a 15% relative reduction in the incidence of major adverse cardiovascular events. However, less is known about the impact of PCSK9i initiation acutely in the setting of an acute coronary syndrome (ACS).

Purpose
To assess the efficacy of early initiation of PCSK9i therapy in lipid parameters among patients presenting with ACS.

Methods
We performed a systematic review and meta-analysis comparing PCSK9i with placebo in the setting of ACS, added to guideline directed high-intensity or maximally tolerated statin therapy. Inclusion was restricted to randomized controlled trials (RCTs) with initiation of PCSK9i or placebo within 1 week of presentation or percutaneous coronary intervention for ACS. PubMed, EMBASE, and Cochrane Central were searched. The systematic review and meta-analysis followed Cochrane and PRISMA recommendations.

Results
Six RCTs with a total of 996 patients were included, of whom 503 (50.5%) received PCSK9i. Mean follow-up ranged from 4 to 52 weeks. Mean time from presentation to administration of first dose ranged from 3.6 hours to 6.5 days. LDL-C levels were significantly lower at follow-up in the PCSK9i group (mean difference [MD] -44 mg/dL; 95% CI -54.3 to -33.8 mg/dL; p&lt;0.001; Figure 1A). Lp(a) was also significantly decreased with PCSK9i therapy (MD -24.0 nmol/L; 95% CI -43.0 to -4.9 nmol/L; p=0.01; Figure 1B). Similarly, total cholesterol (MD -49.2 mg/dL; 95% CI -59 to -39.3 mg/dL; p&lt;0.001) and triglycerides (MD -19 mg/dL; 95% CI -29.9 to -8.2 mg/dL; p&lt;0.001) were significantly reduced with PCSK9i therapy, respectively. HDL-C was marginally increased in this same group (MD 2.5 mg/dL; 95% CI 0.9 to 4.2 mg/dL; p=0.003).

Conclusions
In patients with ACS, early initiation of PCSK9i, in addition to statin therapy, leads to a significant reduction in LDL-C and Lp(a) as compared with placebo. Whether the differences in these lipoproteins translate into a reduction in clinical endpoints is yet to be determined.
SGLT-2 inhibitors are associated with lower rates of mortality following myocardial infarction in patients with type 2 diabetes - A SWEDEHEART observational study
Authors: Rosen H C , Mohammad M A , Jernberg T , Erlinge D 
Published: November 2023

Abstract

Introduction
Secondary prevention following myocardial infarctions is critical in patients with type 2 diabetes due to the substantial risk of adverse events. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce rates of heart failure hospitalisation and cardiovascular death in patients with type 2 diabetes in several randomised studies. We hypothesised that the cardiovascular benefits associated with SGLT2 inhibitors could be observed in patients with diabetes treated with SGLT2 inhibitors following myocardial infarction in a real-world setting.

Methods
We included all patients with type 2 diabetes with an eGFR &gt;30 ml/min/1.73m2 discharged from the cardiac care unit following a type 1 acute myocardial infarction between 1 January 2018 to 15 February 2022 from the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registries and cross-referenced the registry to the National Prescribed Drug Register. We identified all patients with a redeemed SGLT2 inhibitor 365 days prior to admission or within 10 days after discharge from the cardiac care unit. The primary outcome measure was a composite of all-cause death and hospitalisation for heart failure within 1 year from hospital discharge. Follow-up started at discharge.

Results
The study included 12,502 patients, of whom 2,770 (22.2%) were treated with SGLT2 inhibitors. Patients who were prescribed SGLT2 inhibitors were younger but had more comorbidities. The primary endpoint occurred in 2,128 (17.0%) patients during the follow-up period. After adjustment for differences in baseline characteristics and medical therapy, the use of SGLT2 inhibitors was associated with a 15% lower rate of the primary outcome, with an adjusted hazard ratio (HR) of 0.85 (95% CI 0.75 – 0.97). This was primarily driven by a lower rate of all-cause mortality, with an adjusted HR of 0.63 (95% CI 0.51 – 0.79). However, no difference was observed in hospitalisations for heart failure, with an adjusted HR of 1.07 (95% CI 0.93 – 1.22).

Conclusion
Treatment with SGLT2 inhibitors after myocardial infarction in patients with type 2 diabetes was associated with a lower incidence of a composite outcome comprising of all-cause mortality or hospitalisation for heart failure. The lower observed rate appeared to be driven by a lower all-cause mortality rate in those treated with SGLT2 inhibitors.Baseline characteristicsCumulative incidence of the outcome