bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilising clinical data to personlaise boundary conditions significantly improves the accuracy of angiography based virtual FFR
Authors: Gosling R , Gunn E , Wei H L , Gu Y , Rammohan V , Hughes T , Hose D R , Lawford P V , Gunn J P , Morris P D 
Published: October 2021

Abstract

Background
Angiography-derived computed (virtual) fractional flow reserve (vFFR) permits the assessment of coronary physiology without the need for a pressure wire or hyperaemia. However, accuracy is limited by assumptions made about coronary microvascular resistance (CMVR) [1]. We hypothesised that machine learning may allow us to “tune” our estimate of the CMVR to increase the accuracy of vFFR.

Purpose
To determine whether routine clinical data can personalise CMVR and improve the accuracy of vFFR on an individual case basis.

Methods
Patients with chronic coronary syndromes underwent coronary angiography with FFR assessment. Vessel-specific CMVR was computed using a 3D- computational fluid dynamics simulation with invasively measured proximal and distal pressures. Predictive models were created using non-linear autoregressing moving average with exogenous inputs (NARMAX) modelling with computed CMVR as the dependent variable. vFFR was computed using previously described methods [2]. Three simulations were run, using: 1) a generic CMVR value (Model A); 2) a NARMAX-predicted CMVR based upon a panel of simple clinical data (Model B); and 3) a NARMAX-predicted CMVR incorporating echocardiographic data (Model C). The diagnostic and quantitative accuracy of each model was compared with directly measured FFR.

Results
Eighty four patients underwent coronary angiography with FFR assessment in 157 vessels. Mean age was 64 (±0.1) years and 64 (76%) were male. Mean FFR was 0.79 (±0.15). Mean CMVR was 1.01e+10 Pa/m3 s–1. vFFR error with Model A was ±0.10, with Model B was ±0.07 (p&lt;0.001) and with Model C was ±0.05 (p&lt;0.001) (Table 1).

Conclusion
vFFR is dependent upon not only the epicardial stenosis, but also the CMVR, estimation of which can be personalised based upon clinical and echocardiographic data. This can be used to increase the accuracy of vFFR.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): British Heart Foundation Clinial Research Training FellowshipNIHR i4i grant Table 1
Genomic prediction of cardiovascular events in a coronary Southern European population
Authors: Mendonca F , Mendonca M I , Santos M , Temtem M , Sousa J A , Sousa A C , Henriques E , Freitas S , Rodrigues M , Borges S , Guerra G , Drumond A , Palma Dos Reis R ,   GENEMACOR study
Published: October 2021

Abstract

Background
Traditional and clinical risk factors are indicators of atherosclerosis over time and strong independent predictors of cardiovascular events, but it is unknown whether other genetic markers could provide information about the evolution of atherosclerotic coronary artery disease (CAD).

Objective
We propose identifying the genetic predisposition to atherosclerotic plaque progression and events occurrence, through a study cohort from GENEMACOR study population.

Methods
We performed a study with a cohort of 1,712 patients who underwent coronary angiography with more than 70% stenosis of at least one main coronary vessel, during a mean follow-up of 5 years (amplitude range 20 years). 33 SNPs associated with risk of CAD in previous GWAS, were genotyped by TaqMan assays methodology. The best model in the bivariate analysis at 95% CI with all genetic variants was generated, to investigate their association with prognostic and events occurrence. The hazard function at a set of confounding-variables was determined to evaluate their relationship with the event's incidence by the Cox survival analysis regression model. Finally, we constructed Kaplan–Meier cumulative-event curves for the significant variants.

Results
The analysis revealed two SNPs associated with the progression of atherosclerosis and events occurrence: rs12190287 G&gt;C in the TCF21 gene on chromosome 10 (dominant model; OR=1.542; 95% CI 1.069 – 2.224; p=0.020) and the rs1333049 G&gt;C in the CDKN2-AS1 gene on chromosome 9 (recessive model; OR=1.228; 95% CI 1.001 – 1.518; p=0.050). The Kaplan-Meier cumulative event curves in the TCF21 variant rs12190287 G&gt; C showed that the GC+CC vs GG genotype was associated with a worse prognosis (log-rank test, p=0.016) and the CDKN2B-AS1 rs1333049 G&gt; C revealed that the CC vs GG+GC genotype also presented severe prognosis and more events at the end of the follow-up period (log-rank test, p=0.046).

Conclusion
We have identified two SNPs associated with the prognosis of CAD, rs12190287 of TCF21 gene and rs1333049 of CDKN2-AS1 gene. Both are in non-coding enhancer regions and regulate transcriptional mechanisms shared among multiple CAD risk loci and could provide new insights into CAD's pathophysiology identifying core mechanisms for therapeutic intervention modulating the disease risk.

Funding Acknowledgement
Type of funding sources: None.
Frequency and prognostic impact of periprocedural myocardial infarction determined by various MI definitions in patients with chronic coronary syndromes undergoing percutaneous coronary intervention
Authors: Ueki Y , Otsuka T , Bar S , Koskinas K , Losdat S , Heg D , Zanchin T , Siontis G , Praz F , Haner J , Susuri N , Stortecky S , Pilgrim T , Windecker S , Raber L 
Published: October 2021

Abstract

Background
Several definitions of peri-procedural myocardial infarction (MI) requiring different biomarker thresholds with or without ancillary criteria for myocardial ischemia are currently recommended without being fully validated in real-world patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI).

Objectives
We aimed to evaluate the prevalence and prognostic value of high-sensitivity cardiac troponin-based peri-procedural MI according to contemporary MI definitions using a large real-world PCI cohort.

Methods
In CCS patients undergoing elective PCI enrolled to the Bern PCI registry (NCT02241291) between 2010 and 2018, peri-procedural myocardial injury and infarction were assessed according to the 4th and 3rd universal definition of MI (UDMI), academic research consortium (ARC)-2, and Society for Cardiovascular Angiography and Interventions (SCAI) criteria. The primary endpoint was cardiac death at 1 year.

Results
Among 4404 CCS patients, peri-procedural MI defined by the 4th UDMI, 3rd UDMI, ARC-2, and SCAI were observed in 14.9%, 18.0%, 2.0%, and 2.0% of patients, respectively. Cardiac mortality at 1 year in patients with peri-procedural MI defined by 4th UDMI, 3rd UDMI, ARC-2, and SCAI were 3.0%, 2.9%, 5.8%, and 10.0%, respectively. After multivariate adjustments, peri-procedural MI defined by the ARC-2 and SCAI were independently associated with cardiac death at 1 year, while those defined by the 4th and 3rd UDMI were not.

Conclusion
Among CCS patients undergoing PCI, periprocedural MIs defined by theARC-2 and SCAI occurred 7 to 9 times less frequently as compared with the 4th and 3rd UDMI, and were the only definitions significantly associated with cardiac mortality.

Funding Acknowledgement
Type of funding sources: None. Cardiac death at 1 year
Impact of morphine use on mortality in STEMI patients treated with primary PCI – results from a new registry
Authors: Szabo D , Szabo A , Edes I F , Becker D , Merkely B , Hizoh I 
Published: October 2021

Abstract

Background
Opioids decrease the effect of P2Y12 receptor inhibitors in vitro and observational reports suggest that morphine use may be associated with larger infarct size. Our research group showed previously, using a prospective single-centre registry, that periprocedural morphine use may have no impact on long-term mortality in STEMI patients treated with primary PCI and clopidogrel.

Purpose
We aimed to study this in vitro interaction on clinical outcomes in patients who were predominantly treated with the novel P2Y12 inhibitors prasugrel or ticagrelor, according to the current guidelines.

Methods
From May 2020 through February 2021, we collected demographic, anamnestic, procedural and laboratory data of 297 consecutive STEMI cases who were treated with primary PCI at our tertiary centre. Of them 126 patients (42.4%) received IV morphine during the periprocedural period. Outcome measure was time to all-cause mortality. The median follow-up time was 147 days (IQR 71–242 days), with 39 events. To adjust for confounding, a 1:1 propensity score-matching analysis (PSM) was performed using 186 cases. Absolute difference in survival was analysed using Kaplan-Meier survival curves and the logrank test, whereas the relative change was assessed by univariable Cox regression.

Results
An adequate balance on baseline covariates was achieved by the propensity score-matching. Kaplan-Meier analysis showed no statistically significant difference in all-cause mortality of the treatment groups neither in the original nor in the propensity score-matched population (p=0.220 and 0.762 respectively). In the matched population we found no difference in survival as the HR (Morphine/No Morphine) was 0.88 (95% confidence interval [CI]: 0.39–2.00), p=0.76.

Conclusion
Our preliminary data suggest that morphine may have no impact on mortality in STEMI patients treated with primary PCI and medical therapy according to the current guidelines including novel P2Y12 antagonists.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The research was supported by the Ministry of Innovation and Technology NRDI Office within the framework of the Artificial Intelligence National Laboratory Program. Kaplan-Meier curves: Original populationKaplan-Meier curves: PSM population
Risk scores for risk stratification in chronic coronary syndrome and their improvement by Gensini and SYNTAX scores
Authors: Blaum C , Bay B , Kroeger F , Gossling A , Lorenz T , Max L , Zeller T , Schnabel R , Clemmensen P , Westermann D , Kirchhof P , Blankenberg S , Seiffert M , Brunner F J , Waldeyer C 
Published: October 2021

Abstract

Introduction
There is a substantial residual risk in patients with chronic coronary syndrome (CCS). Risk scores could be useful tools to allocate intensified secondary preventive medications to address this residual risk. Whether their predictive value can be improved by addition of angiographic scores of the extent of coronary artery disease (CAD) is unknown.

Purpose
To test and compare the predictive value of three externally developed risk scores for CAD and to investigate the effect of addition of SYNTAX and Gensini scores.

Methods
We tested the TIMI risk score for secondary prevention (TRS 2°P), a risk score derived from the INVEST study, and the ABC-CHD model (see references 1–3) in 1280 patients with CCS from a contemporary observational CAD cohort ongoing since 2015 with a median follow-up of 3.6 years. In a second step we added SYNTAX and Gensini scores to the models. The endpoints tested were cardiovascular death and major adverse cardiovascular events (MACE), consisting of cardiovascular death, myocardial infarction and ischemic stroke.

Results
All investigated scores yielded continuously increasing event rates for MACE and cardiovascular death with increasing score points obtained. As an example Figure 1 displays 3-year rates for cardiovascular death and MACE against the points obtained in the TRS 2°P, whilst also displaying the distribution of patients amongst the risk categories. The three scores showed modest predictive value for occurrence of cardiovascular death (c-indices 0.60, 0.64, 0.70 for TRS 2°P, INVEST score, ABC-CHD score, respectively). Addition of both SYNTAX and Gensini scores to the models yielded c-indices of 0.66, 0.69 and 0.70 respectively (Figure 2a). Similar predictive values were observed for the occurrence of MACE (c-indices 0.59, 0.60, 0.64 for TRS 2°P, INVEST score, ABC-CHD score, respectively) as well after addition of both SYNTAX and Gensini scores (c-indices 0.62, 0.63, 0.64, see Figure 2b).

Conclusion
(I) Currently available risk scores are modestly predictive for the occurence of cardiovascular events in patients with CCS. (II) Addition of Gensini and SYNTAX scores improves their predictive value particularly in weaker risk scores.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2a (left) and 2b (right)
Prevalence of familial hypercholesterolemia in patients presenting with premature acute coronary syndrome
Authors: Hauguel M , Aidan V , Hergault H , Beauchet A , Pepin M , Prati G , Pilliere R , Ouadahi M , Josseran L , Rodon C , Rabes J P , Dubourg O , Massy Z , Mansencal N 
Published: October 2021

Abstract

Background
Familial hypercholesterolemia (FH) is a common genetic disorder responsible for premature and severe cardiovascular morbidity and mortality. The FH prevalence in patients who experienced a premature acute coronary syndrome (ACS) ranges from 5 to 50% according to previous studies and no comparison with FH prevalence in general population are available in those studies.

Purpose
We aimed to assess the prevalence of clinical FH among patients with premature acute myocardial infarction (MI) (age ≤50 years) and to compare it with FH prevalence in a control population (age ≤50 years), coming from the same population pool.

Methods
Patients with diagnosis of premature MI (age ≤50 years) referred to Ambroise Paré hospital from 2014 to 2018 were included. FH prevalence was estimated via the Dutch Lipid Clinic Network score, based on personal and familial history of premature cardiovascular disease, and LDL-cholesterol levels. FH was “possible” with a score between 3 and 5 points, “probable” with a score between 6 and 8 and “definite” with a score &gt;8 and no FH was defined as a score &lt;3. FH prevalence in patients with MI was compared to FH prevalence in a general population (age ≤50 years), coming from the prospective cohort CARVAR 92.

Results
Among the 457 patients with premature MI, 220 (48%) patients had no FH, 208 (46%) had a “possible” FH and 29 (6%) had a “probable” or “definite” FH. In the control population, 9900 subjects aged ≤50 years were identified: 9343 (94.37%) had no FH, 541 (5.46%) had a “possible” FH and 16 (0.16%) had a “probable” or “definite” FH. Considering subjects with “probable” or “definite” FH, FH prevalence was 37.5 times greater among patients with premature MI than in control population (p&lt;0.0001).

Conclusion
Familial hypercholesterolemia is &gt;30-fold more common in patients referred for premature MI than in general population of the same age, coming from the same population pool. This highlights the need for FH diagnosis after a first episode of MI to enhance lipid-lowering therapy and allow an early identification of family members.

Funding Acknowledgement
Type of funding sources: None.
Value of magnetocardiography in chronic coronary disease detection: results of multicenter trial
Authors: Chaikovsky I , Li T , Zhang W , Kazmirchyk A , Mjasnikov G , Lutay M , Lomakovsky O , Wenming J 
Published: October 2021

Abstract

Background
Diagnostic management of patients with chest pain remains a clinical challenge. Magnetocardiography (MCG) is non-invasive evaluation of the magnetic field of the heart that is produced by the electric activity of the myocardium. Previous studies have clearly demonstrated the potential of MCG in coronary artery disease (CAD) detection.
The objective of this multicenter trial is the investigation of value of MCG in diagnosis of mild and severe coronary artery disease using novel approach of magnetocardiographic current density vectors (CDV) maps evaluation.

Methods
This clinical trial was conducted in three GCP accredited institutions under the leadership of a General Hospital in China. The trials were designed for paired experiments with multi-center blind interpretation. Coronary angiography and coronary flow reserve fraction were used as a “gold standard”.
In total 133 persons (mean age 59±3,1 years), divided into 3 groups, were examined. The first group (61 subjects) was identified for patients with severe myocardial ischemia and met the criteria for revascularization: degree of coronary artery stenosis is ≥80% or coronary blood flow reserve score ≤0,8.
The second group (13 subjects) is patients whose myocardial ischemia is confirmed but has not yet reached the criteria for revascularization: coronary artery stenosis is between 50% and 80%, coronary blood flow reserve score &gt;0,8.
The third group (59 subjects) is whom the “gold standard” confirmed that there is no coronary artery disease. This group is called the negative control group.
The MCG examination was performed using a 7-channel MCG system located in an unshielded room. Magnetocardiography recordings were taken from 36 positions at rest Based on the magnetic field distribution, set of subsequent current vectors maps were reconstructed with equidistant time step (10 ms) within the ST-T interval. Each of these maps was classified into two categories: normal map or pathological map. This classification is based on the analysis of the of the largest current density vectors direction and dipole or non-dipole structure of the map. Then, portion of pathological CDV maps within the ST-T interval was defined. Based of this portion, each MCG examination was was assigned to one of 3 groups: mild CAD, severe CAD or no CAD.

Results
The coincidence rate of each group was as follows: coincidence rate of severe CAD – 85,45%, coincidence rate of mild CAD – 77,78%, coincidence rate of control group was 87,10%. Sensitivity 93,75% and specificity 87,10% were achieved, PPS was 88,24%, NPV 93,10%. In terms of likelhood ratio results were as follows: a positive likelhood ratio of 7.27, negative likelhood ratio – 0.07.

Conclusion
MCG-examination seems to be a reliable method in the diagnosis of chronic severe and mild CAD. Further large-scale studies needed to confirm these findings.

Funding Acknowledgement
Type of funding sources: None.
The effect of immediate coronary angiography after cardiac arrest without ST-segment elevation on left ventricular function. A sub-study of the COACT randomised trial
Authors: Lemkes J , Spoormans E M , Demirkiran A , Leutscher M S G , Janssens G N , Van Der Hoeven N W , Jewbali L S D , Dubios E , Meuwissen M , Bosker H , Bleeker G , Vlachojannis G , Van De Ven P , Van Loon R , Van Royen N ,   COACT investigators
Published: October 2021

Abstract

Background
The effect of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients who are successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) on left ventricular function is currently unknown.

Purpose
To evaluate whether immediate coronary angiography and PCI improves left ventricular function in patients who are successfully resuscitated from cardiac arrest without STEMI.

Methods
This prespecified sub-study of the multicentre COACT trial evaluated 552 patients, successfully resuscitated from out-of-hospital cardiac arrest without signs of STEMI. Patients were randomized to either undergo immediate coronary angiography or delayed coronary angiography, after neurologic recovery. All patients underwent PCI if indicated. The main outcomes of this analysis were left ventricular ejection fraction and end-diastolic and systolic volumes assessed by cardiac magnetic resonance imaging or echocardiography.

Results
Data on left ventricular function was available for 397 patients. The mean (± standard deviation) left ventricular ejection fraction was 45.2% (±12.8) in the immediate angiography group and 48.4% (±13.2) in the delayed angiography group (mean difference: −3.19; 95% confidence interval [CI], −6.75 to 0.37). Median left ventricular end-diastolic volume was 177 ml in the immediate angiography group compared to 169 ml in the delayed angiography group (ratio of geometric means: 1.06; 95% CI, 0.95 to 1.19). In addition, mean left ventricular end-systolic volume was 90 ml in the immediate angiography group compared to 78 ml in the delayed angiography group (ratio of geometric means: 1.13; 95% CI 0.97 to 1.32).

Conclusion
In patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, immediate coronary angiography was not found to improve left ventricular dimensions or function compared with a delayed angiography strategy.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Netherlands Heart InstituteBiotronikAstraZeneca
CSL112 (human apolipoprotein A-I) infusion rapidly increases apoA-I exchange rate (AER) when administered to patients post myocardial infarction
Authors: Kingwell B A , Velkoska E , Diditchenko S , Greene B H , Wang S , Mears J , Wright S D , Gibson C M , Smith J D 
Published: October 2021

Abstract

Background
Cholesterol efflux capacity (CEC) measured using patient serum and cultured macrophages is considered a biomarker of high-density lipoprotein (HDL) functionality. This parameter is inversely related to incident cardiovascular events and declines in the days post-acute myocardial infarction (AMI). The apolipoprotein A-I (apoA-I) exchange rate (AER) may represent an alternative, clinically amenable cell-free measure of CEC, which has also been associated with incident cardiovascular events (1).

Purpose
To characterise the effects of human apoA-I (CSL112) infusion on AER over 48 hours when administered post AMI.

Methods
This analysis included 50 patients with available samples from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) randomized, double-blind, placebo-controlled, phase 2b pharmacokinetic/pharmacodynamic sub-study (2). Patients were randomized to receive four weekly infusions of either placebo (n=16), 2g (n=19) or 6g (n=15) CSL112 post AMI. Blood samples were drawn at baseline and at 2, 4, 6, 12, 24 and 48 hours post the first and fourth infusion for measurement of AER (1) as well as CEC (total, ABCA1 dependent and ABCA1 independent CEC) as previously described (3).

Results
CSL112 infusion increased AER dose-dependently, peaking at 2h (end of infusion) and returning to baseline by 24h post infusion (Figure 1). AER was significantly correlated with CEC (total, ABCA1 dependent and independent), HDL-cholesterol, apoA-I and phosphatidylcholine across all timepoints and similarly after both infusions (Table 1).

Conclusion
Infusion of CSL112 increased AER in a dose-dependent manner post AMI and may represent a clinically amenable biomarker of HDL functionality.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): CSL Ltd, Parkville, Australia Figure 1. Left: Time course data expressed as mean ± SEM and adjusted for baseline prior to each infusion. Using a linear mixed model for repeated measures, the 6g dose increased AER from baseline at timepoints from 2–12 hours (p&lt;0.001), whereas the 2gm dose only increased AER between 2–6 hours (p&lt;0.05). Right: Boxplots showing median, quartiles and min/max of Area Under the Curve (AUC) from 0–24 hours post infusion. Using one-way ANOVA the 6 g dose was significantly higher than placebo (p&lt;0.05).Table 1