bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assay of macrotroponin I not complexed with troponin T: effect on the performance of troponin T to predict myocardial infarction
Authors: Pemberton C J , Raudsepp S D , Lee J A , Wise J , Jina K , Powell J , Aldous S , Troughton R , Pickering J , Than M , Peacock F W , Richards A M 
Published: November 2023

Abstract

Background
Cardiac troponin-immunoglobulin (Ig) complexes (macrotroponin) can interfere with cardiac troponin (cTn) test performance. However, the role of this interference has not been fully explored. We developed a specific, novel, 2-hour prototype immunoassay of monomer IgG-bound TnI (bTnI-IgG). Using this assay, our purpose was to examine the potential contribution of cTnT binding to macro-TnI, and report its effects on the clinical diagnostic and predictive performance of highly sensitive TnT (hs-TnT) and TnI (hs-TnI) assays.

Methods
Using the bTnI-IgG assay, we evaluated EDTA blood samples taken at presentation (t=0) from two ED acute chest pain studies; SPACE (n=1066) and FAST-TRAC (n=1440), with statistical analysis (logistic regression, ROC curves), to AMI and 1-year outcomes, alone and in combination, with hsTnT (Roche) and hsTnI (Abbott/Beckmann) tests. Pathway analysis was used to identify if single bTnI-IgG measurements improve risk stratification in low and high AMI risk.

Results
In individual and combined study datasets, bTnI-IgG concentrations in patients with adjudicated acute MI (n=336) were lower than all other diagnoses (p&lt;0.001). Singularly, and in multivariable models containing hs-TnT or hs-TnI concentrations, bTnI-IgG was an independent predictor of MI. Amongst all patients with MI not ruled-out on presentation (hs-TnT &gt;5ng/L) and not high-risk (hsTnT&lt;14ng/L), the addition of bTnI-IgG to a model containing hs-TnT, HxMI and sex improved discrimination (AUC increase of 0.014 (95%CI: 0.004 to 0.025) from 0.788 to 0.802, p=0.009). Within a diagnostic pathway analyses of n=2126 matched patient data points, adding presentation bTnI-IgG measurement alone to an MI risk stratification model consisting of hs-TnT ≤URL, HxMI and sex yielded 14% more low risk patients identified (n=586 v 667 patients) through improved specificity (77% to 88%) whilst maintaining an overall sensitivity of &gt;99%. bTnI-IgG also predicted 1-year mortality and new stroke in all patients (Odds Ratios 0.292 [95%CI 0.130 to 0.654] p=0.009) and 0.255 ([95%CI 0.078 to 0.834] p=0.024), respectively.

Conclusions
Measurement of bTnI-IgG that is free from cTnT could potentially improve ED presentation diagnostic test performance and risk stratification of MI patients using criteria that includes hs-TnT. No effects upon hs-TnI assays were observed. This data suggests current hs-TnT test design and measurements may be impacted by binding interactions between TnT and TnI. Finally, bTnI-IgG can independently predict mortality and stroke outcomes within 1 year of index presentation.
Does a high baseline high sensitivity cardiac troponin T allow for the early diagnosis of acute myocardial infarction?
Authors: Knott J , Ola O , De Michieli L , Akula A , Yang E , Gharacholou M , Lewis B , Mehta R , Sandoval Y , Jaffe A 
Published: November 2023

Abstract

Background
Guidelines suggest that the diagnosis of acute myocardial infarction (MI) is likely when high concentrations of high-sensitivity cardiac troponin (hs-cTn) are present in the initial sample. These concentration thresholds are much higher than the 99th percentile and are said to provide a high positive predictive value (PPV) for acute MI1.

Purpose
Evaluate the PPV of recommended baseline hs-cTnT thresholds (&gt;52 and &gt;100 ng/L) for the diagnosis of acute MI from our multi-center United States (US) experience.

Methods
Retrospective, multicenter (n=22), observational biomarker study involving consecutive, adult patients presenting to the emergency department (ED) in whom at least 1 hs-cTnT measurement was obtained within 12 hours of presentation (CV DataMart Biomarker cohort). The primary endpoint was also evaluated in an adjudicated cohort of consecutive patients presenting to the ED with at least 1 hs-cTnT &gt;99th percentile (ACTION cohort). These cases were adjudicated based on the Fourth Universal Definition of MI by trained physicians. The primary efficacy endpoint was the PPV of acute MI (type 1 or 2), type 1 MI and type 2 MI during index hospitalization using baseline hs-cTnT thresholds of &gt;52 ng/L and &gt;100 ng/L.

Results
The CV DataMart Biomarker cohort consisted of 143,709 patients, amongst whom 3,003 (2.1%) were diagnosed with acute MI using ICD codes. In the CV DataMart Biomarker cohort, baseline hs-cTnT concentrations of &gt;52 ng/L and &gt;100 ng/L resulted in PPVs of 12% (95% CI: 11, 12) and 17% (95% CI: 17, 19) for acute MI, respectively. In patients with chest pain and baseline hs-cTnT concentrations &gt;52 ng/L, PPV for acute MI was 17% (95% CI: 15, 18), and in those with hs-cTnT concentrations &gt;100 ng/L, PPV was 22% (95% CI: 19, 25). The adjudicated ACTION cohort consisted of 2,107 patients, amongst whom 155 (7.4%) were diagnosed with acute MI including 64 (41%) with type 1 MI and 91 (59%) with type 2 MI. In the ACTION cohort, baseline hs-cTnT concentrations of &gt;52 ng/L and &gt;100 ng/L resulted in PPVs of 46% (95% CI: 40, 53) and 62% (95% CI: 53, 70) for acute MI, respectively. In patients with chest pain and baseline hs-cTnT concentrations &gt;52 ng/L, PPV was 67% (95% CI: 57, 76) for acute MI, 52% (95% CI: 41, 62) for type 1 MI and 15% (95% CI: 8.4, 24) for type 2 MI. In those with chest pain and baseline hs-cTnT concentrations &gt;100 ng/L, PPV was 77% (95% CI: 65, 87) for acute MI, 64% (95% CI: 51, 75) for type 1 MI and 14% (95% CI 6.4, 24) for type 2 MI (Figure).

Conclusion
Using previously recommended high-risk hs-cTnT thresholds of 52 and 100 ng/L in US patients provides reasonable performance to rule-in acute MI when used in patients with chest pain. When used more broadly across all-comers, the diagnostic performance is poor.
Fractional flow reserve and fractional flow reserve gradient from coronary CT angiography for future coronary events
Authors: Hong D , Dai N , Lee S H , Shin D , Choi K H , Kim S M , Park T K , Yang J H , Song Y B , Hahn J Y , Choi S H , Choe Y H , Gwon H C , Ge J , Lee J M 
Published: November 2023

Abstract

Background
Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) is per-vessel index reflecting cumulative hemodynamic burden while percutaneous coronary intervention is per-lesion treatment that relieves ischemia in a focal lesion.

Purpose
We sought to evaluate additive prognostic value of local gradient of FFRCT (FFRCT gradient) in addition to FFRCT to predict future coronary events.

Methods
The current study included 239 patients (617 vessels) who underwent CCTA within 6-36 months prior to index angiography, of which 202 vessels had future coronary events and 415 vessels did not. Future coronary events were defined as a composite of vessel-specific myocardial infarction or urgent revascularization during mean interval of 1.5 years. Preexisting disease patterns were classified according to cumulative burden and local severity of coronary atherosclerosis, expressed as FFRCT ≤0.80 and FFRCT gradient ≥0.025/mm, respectively.

Results
Both FFRCT (per 0.01 decrease; HR 1.039, 95% CI 1.029-1.050, P&lt;0.001) and FFRCT gradient (per 0.01 increase; HR 1.140, 95% CI 1.096-1.185, P&lt;0.001) were significantly associated with the risk of future coronary events. Severe local disease defined by FFRCT gradient≥0.025/mm showed significantly higher risk of future coronary events than FFRCT gradient&lt;0.025/mm in both FFRCT&gt;0.80 (52.2% vs. 29.4%, HR 2.212, 95% CI 1.357-3.607, P=0.001) and FFRCT≤0.80 groups (59.6% vs. 39.4%, HR 1.894, 95% CI 1.255-2.856, P=0.002). Adding FFRCT gradient into model with FFRCT alone showed significantly increased predictability for future coronary events (global chi-square 43.1 vs. 37.5, P=0.018), and physiologic classification of disease patterns integrating both FFRCT and FFRCT gradient was independent predictor of future coronary events (HR 1.325, 95% CI 1.135-1.548, P&lt;0.001).

Conclusions
Patients with severe local disease defined by high FFRCT gradient showed significantly increased risk of future coronary events irrespective of FFRCT. Integrating both FFRCT and FFRCT gradient showed incremental predictability for future coronary events than FFRCT alone.Graphic Abstract
ARCANGELO: an observational, prospective study with acute coronary syndrome patients undergoing percutaneous coronary intervention who receive cangrelor transitioning to oral P2Y12 inhibitors
Authors: De Luca L , Calabro P , Capranzano P , Musumeci G , Di Mario C , Bolognese L 
Published: November 2023

Abstract

Background
The use of oral platelet P2Y12 receptor inhibitors, to reduce the risk of thrombotic complications related to Percutaneous Coronary Intervention (PCI), have some limitations in the acute phase, e.g., the delayed onset of action and lack of bioavailability in critical patients. Cangrelor is the only intravenous P2Y12 inhibitor, which based on its quick onset and offset of action is a valid alternative option for antiplatelet therapy, particularly for patients who are unable to take oral medications or for whom oral administration is not adequate. Notably, during the clinical development program of cangrelor, ticagrelor and prasugrel were not marketed and, therefore, the pivotal studies were conducted only with transitioning to clopidogrel. The aim of ARCANGELO study was the evaluation of the safety and effectiveness of cangrelor when administered to patients with Acute Coronary Syndrome (ACS) undergoing PCI in a real-world setting, including patients who received cangrelor transitioning to either clopidogrel, prasugrel, or ticagrelor.

Methods
Adult patients eligible to PCI for ACS who received cangrelor and who consented to take part in the study in 28 Italian centers, were followed in the 30 days after PCI. Bleedings, major adverse cardiac events (MACEs), and adverse events were recorded. The primary outcome was the incidence of any bleedings, according to BARC (Bleeding Academic Research Consortium) criteria, at 30 days post-PCI.

Results
A total of 1,004 patients were enrolled and 995 (99.2%) patients were eligible for analysis. Median (IQR) age was 65 (56-73) years, and 771 (77.5%) patients were males. 597 (59.9%) patients had ST-segment Elevation Myocardial Infarction; 509 (51.2%) patients had multi-vessel vessel coronary artery disease. A radial artery access was used in 926 (93.1%) patients and drug-eluting stents were implanted in almost all patients (n=972, 97.7%). All 995 patients included in the analysis received 30 micrograms/kg by intravenous bolus and 4 micrograms/kg/min by intravenous infusion. 730 patients (73.4%) were then transitioned to ticagrelor, 127 (12.8%) to prasugrel, and 138 (13.9%) to clopidogrel. 52 (5.2%) (95% CI 3.9% - 6.8%) patients experienced at least one bleeding event up to 30 days post-PCI. Five patients (0.5%) experienced at least one BARC type 3-5 (moderate-severe) bleeding (all type 3). Fourteen (1.4%) patients presented with at least one MACEs during observation (6 [0.6%] death, 7 [0.7%] myocardial infarction, 2 [0.2%] stent thrombosis). Six (0.6%) patients experienced at least one Treatment-Emergent Adverse Events related to cangrelor.

Conclusions
The results of this large real-world evidence study confirm that the use of cangrelor in patients with ACS undergoing PCI and transition strategy to the currently used P2Y12 oral inhibitors is safe and effective in daily practice.
Prognostic value of a novel artificial intelligence-based coronary computed tomography angiography-derived ischemia algorithm for patients with suspected coronary artery disease
Authors: Baer S , Nabeta T , Maaniitty T , Bax J J , Saraste A , Earls J , Min J K , Knuuti J 
Published: November 2023

Abstract

Introduction
Coronary computed tomography angiography (CCTA) has emerged as the first-line, non-invasive imaging tool to detect coronary artery disease (CAD) in patients with low to intermediate pre-test probability of CAD. However, CCTA cannot directly assess the presence of ischemia, which may lead to further downstream testing. A novel artificial-intelligence (AI)-based algorithm, comprising a machine-learned method that leverages atherosclerosis and vascular morphology features to determine vessel-level coronary ischemia from CCTA images, may be useful in this regard.

Purpose
We aimed to investigate the prognostic value of the AI-based ischemia algorithm for clinical events among symptomatic patients with suspected CAD referred for CCTA.

Methods
The AI-based ischemia algorithm was calculated by analysts blinded for patient characteristics and clinical outcomes using CCTA data from patients with suspected CAD who underwent clinically indicated CCTA at a large tertiary care center from February 2007 to December 2016. The primary endpoint was the composite of death, myocardial infarction (MI), and unstable angina pectoris (uAP) throughout a median follow-up of 8.1 years (IQR 6.0-9.6). Secondary endpoints were the association between the AI-based ischemia algorithm and the primary endpoint among patients with no/non-obstructive (i.e. ≤50%) CAD vs. obstructive (i.e. &gt;50% stenosis) CAD in CCTA.

Results
1574 patients were evaluated by the AI-based ischemia algorithm and 1540 were analyzable. Patients with positive AI-based ischemia findings (30.4%, n=468) had a significantly higher crude rate of the primary endpoint as compared to patients with negative AI-based ischemia findings (69.6%, n=1072) (HR 2.37, 95% CI 1.80-3.11, p&lt;0.001), driven by higher rates of all endpoint composites (death: HR 1.48, 95% CI 1.13-2.22, p=0.007; MI: HR 5.42, 95% CI 3.10-9.49, p&lt;0.001; uAP: HR 6.76, 95% CI 3.01-15.20, p&lt;0.001). Results were consistent after adjusting for clinical confounders (age, sex, diabetes mellitus, smoking, hypertension, dyslipidemia, BMI&gt;25 kg/m2, CAD family history) (primary endpoint: HR 1.66, 95% CI 1.24-2.22, p=0.001). Positive AI-based ischemia findings were associated with a significantly higher rate of the primary endpoint among patients with no/non-obstructive CAD in CCTA (n=1001/1487) (HR 2.56, 95% CI 1.53-4.27, p&lt;0.001), but not among those with anatomically obstructive CAD in CCTA (n=486/1487) (HR 1.08, 95% CI 0.70-1.66, p=0.715).

Conclusions
A novel AI-based CCTA-derived ischemia algorithm was associated with a 1.7-fold increased adjusted rate of long-term death, MI, or uAP. This AI-based ischemia algorithm may be helpful to improve risk stratification, especially among patients with normal/non-obstructive CCTA.Kaplan Meier CCTA ≤50% and &gt;50% stenosis
Clinical impact of high platelet reactivity in patients with atrial fibrillation and concomitant percutaneous coronary intervention on dual or triple antithrombotic therapy
Authors: Berteotti M , Gori A M , Giusti B , Fortini A , Grossi G , Ciardetti N , Migliorini A , Lotti E , Valenti R , Di Mario C , Marchionni N , Marcucci R 
Published: November 2023

Abstract

Background
High platelet reactivity (HPR) on clopidogrel is an established thrombotic risk factor after percutaneous coronary intervention (PCI). The introduction of more potent antiplatelet drugs has partially surpassed this issue. However, in the setting of concomitant atrial fibrillation (AF) and PCI clopidogrel is still the most adopted P2Y12 inhibitor.

Purpose
We sought to evaluate the possible clinical relevance of genetic and platelet function testing (PFT) in a real-world population with concomitant AF and PCI on dual (DAT) or triple (TAT) antithrombotic therapy.

Methods
All consecutive patients with history of AF discharged from our cardiology ward with DAT or TAT after a PCI from April 2018 to March 2021 were enrolled in an observational registry. For all subjects, blood serum samples were collected and tested for platelet reactivity by arachidonic acid and ADP (VerifyNow system) and genotyping of the CYP2C19*2 loss-of-function polymorphism. We recorded at 3 and 12-months follow-up: (1) major adverse cardiac and cerebrovascular events (MACCE), (2) major hemorrhagic or clinically relevant non-major bleeding and (3) all-cause mortality.

Results
A total of 147 patients were included (91, 62% on TAT). In 93.4% of patients, clopidogrel was chosen as P2Y12 inhibitor. P2Y12 dependent HPR resulted an independent predictor of MACCE both at 3 and 12 months (HR 2.93, 95% C.I. 1.03 to 7.56, p=0.027 and HR 1.67, 95% C.I. 1.20 to 2.34, p=0.003, respectively). At 3-months follow-up the presence of CYP2C19*2 polymorphism was independently associated with MACCE (HR 5.21, 95% C.I. 1.03 to 26.28, p=0.045).

Conclusions
In a real-world unselected population on TAT or DAT, the entity of platelet inhibition on P2Y12 inhibitor is a potent predictor of thrombotic risk, suggesting the clinical utility of this laboratory evaluation for a tailored antithrombotic therapy in this high-risk clinical scenario.
Ticagrelor versus Clopidogrel in diabetes patients afflicted with acute coronary syndrome stratified by renal function
Authors: Wang T , Shyu K 
Published: November 2023

Abstract

Background
Ticagrelor has been recommended in place of clopidogrel as part of dual antiplatelet therapy (DAPT) in diabetic patients with acute coronary syndrome (ACS). Chronic kidney disease (CKD) patients also have a worse prognosis in the setting of ACS, but the safety and efficacy data for the use of P2Y12 inhibitors in moderate to severe CKD patients (eGFR &lt;60 mL/min/1.73m2) are insufficient.

Purpose
There has been limited data on the outcome of prescribing ticagrelor compared to clopidogrel in ACS-DM patients with chronic kidney disease (CKD).

Methods
This prospective, nationwide, multi-center, observational study, the Acute Coronary Syndrome-Diabetes Mellitus Registry (ACS-DM Registry) was compiled from consecutive patients between October 1, 2013 and September 30, 2016. The primary end point was repeated revascularisation and the composite outcome was CV death, repeat revascularisation and CV-related readmission, was stratified by renal function stages. The Cox proportional hazards models and propensity score models were applied to six-months, one-year, and two-year post ACS, respectively.

Results
There were 539 patients with moderate to severe CKD or on dialysis identified from ACS-DM Registry. There were 451 patients eligible for inclusion criteria of which 116 patients were taking ticagrelor and 335 patients were taking clopidogrel. At our two-year follow-up, the unadjusted incidence of primary end point resulted higher in Ticagrelor group (HR 2.09, 95% CI 1.37-3.18, p = 0.001). After adjustment, ticagrelor also had poor primary end point event and composite outcome as compared to clopidogrel (HR 2.24, 95% CI 1.36-3.68, p = 0.002; HR 1.63, 95% CI 1.06-2.48, p = 0.024, respectively). In regards to the repeated revascularisation issue, the clopidogrel was preferable within the eGFR strata (CKD stage III: HR 2.53, 95% CI 1.32-4.84, CKD stage IV: 1.06 (0.09-12.51), CKD stage V: 1.91 (0.80-4.59), P for interaction=0.684).

Conclusions
Cardiovascular benefits associated with ticagrelor may not be as significant as in the landmark trial. Our results show that patients taking ticagrelor was associated with increased CV events as compared to clopidogrel in ACS-DM patients with stage III-V CKD.propensity score matchingForest plots
Almost 1 in 2 patients with acute coronary syndrome are extremely high-risk and potential candidates for in-hospital triple lipid-lowering therapy: data from the CALLINICUS-Hellas Registry
Authors: Rallidis L , Kalogeras P , Leventis I , Tsamoulis D , Tasoulas D , Zapantiotis D , Kalantzis C , Malkots B , Bouratzis V , Delakis I , Potoupni V , Eleutheriou D , Daios S , Papathanasiou K , Vlachopoulos C 
Published: November 2023

Abstract

Introduction
The great heterogeneity of acute coronary syndrome (ACS) patients in the risk for cardiovascular events recurrence, prompted a recent position paper endorsed by the International Lipid Expert Panel to propose criteria, i.e. coexistence of multivessel coronary artery disease (CAD), polyvascular disease, heterozygous familial hypercholesterolemia (heFH), diabetes mellitus (DM) with estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73 m2 and/or lipoprotein (a) [Lp(a)] &gt;50 mg/dL etc., which define the extremely high-risk ACS patients for whom an low-density lipoprotein cholesterol (LDL-C) &lt;40 mg/dL was proposed.

Purpose
To estimate the proportion of patients with ACS that fulfill the criteria of the extremely high-risk group and are potential candidates for "extremely" intensive early lipid-lowering therapy (LLT) aiming at an LDL-C &lt;40 mg/dL.

Methods
We recruited 780 consecutive patients with ACS who were participants of the CALLINICUS-Hellas Registry which is a prospective multicenter observational study that explores the adherence to LLT, the achievement of LDL-C targets and the cardiovascular events at 6- and 24-months after hospital discharge of patients with ACS.

Results
The prevalence of high risk components was: heFH 13.5%, multivessel CAD 44%, polyvascular disease 3.2%,and DM with eGFR &lt;60 ml/min/1.73 m2 and/or Lp(a) &gt;50 mg/dL 8.1%. By excluding the overlapping between these conditions, 430 ACS patients (55.1%) had at least one of the characteristics which define the extremely high-risk patients (Figure). Presuming a 65% LDL-C reduction of the levels (the pretreatment if on LLT prior admission or the admission if not on prior LLT) of the extremely high-risk ACS patients by taking a maximum dual LLT (intense statin plus ezetimibe), 312 patients, i.e., 40% of all initially recruited patients would fail to achieve an LDL-C &lt;40 mg/dL suggesting that they require additional LLT, namely, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i).

Conclusions
Almost 1 in 2 patients with ACS have extremely high-risk characteristics and are candidates for in-hospital triple LLT (statin plus ezetimibe plus PCSK9i) aiming at an LDL-C &lt;40 mg/dL, a strategy shown to improve plaque stability and possibly to reduce the recurrence rate of early coronary events.Figure