Construction of genetic classification model for coronary atherosclerosis heart disease using three machine learning methods.

BACKGROUND: Although the diagnostic method for coronary atherosclerosis heart disease (CAD) is constantly innovated, CAD in the early stage is still missed diagnosis for the absence of any symptoms. The gene expression levels varied during disease development; therefore, a classifier based on gene expression might contribute to CAD diagnosis. This study aimed to construct genetic classification models for CAD using gene expression data, which may provide new insight into the understanding of its pathogenesis. METHODS: All statistical analysis was completed by R 3.4.4 software. Three raw gene expression datasets (GSE12288, GSE7638 and GSE66360) related to CAD were downloaded from the Gene Expression Omnibus database and included for analysis. Limma package was performed to identify differentially expressed genes (DEGs) between CAD samples and healthy controls. The WGCNA package was conducted to recognize CAD-related gene modules and hub genes, followed by recursive feature elimination analysis to select the optimal features genes (OFGs). The genetic classification models were established using support vector machine (SVM), random forest (RF) and logistic regression (LR), respectively. Further validation and receiver operating characteristic (ROC) curve analysis were conducted to evaluate the classification performance. RESULTS: In total, 374 DEGs, eight gene modules, 33 hub genes and 12 OFGs (HTR4, KISS1, CA12, CAMK2B, KLK2, DDC, CNGB1, DERL1, BCL6, LILRA2, HCK, MTF2) were identified. ROC curve analysis showed that the accuracy of SVM, RF and LR were 75.58%, 63.57% and 63.95% in validation; with area under the curve of 0.813 (95% confidence interval, 95% CI 0.761-0.866, P < 0.0001), 0.727 (95% CI 0.665-0.788, P < 0.0001) and 0.783 (95% CI 0.725-0.841, P < 0.0001), respectively. CONCLUSIONS: In conclusion, this study found 12 gene signatures involved in the pathogenic mechanism of CAD. Among the CAD classifiers constructed by three machine learning methods, the SVM model has the best performance.

Avaliação do perfil de metilação dos genes LDLR, PCSK9, LDLRAP1 em pacientes portadores de hipercolesterolemia familial / Evaluation of the methylation profile of LDLR, PCSK9, LDLRAP1 genes in patients with familial hypercholesterolemia

As variabilidades genotípicas que determinam algumas alterações fenotípicas e metabólicas podem ter seu diagnostico falho se baseado apenas nos dados genômicos. Na hipercolesterolemia familial (HF) pode-se observar que os dados de variantes nos genes da LDLR, PCSK9, APOB e LDLRAP1 sugeridos pelos consensos atuais para confirmar o diagnóstico, tem mostrado serem insuficientes, mostrando baixa porcentagem de confirmação, mesmo nos dos casos em que características fenotípicas apresentam dados sugestivos importantes. A complementação no auxílio diagnóstico com dados epigenéticos tem sido sugerida em muitas doenças, principalmente nas crônicos degenerativos. A metilação do DNA pode estar envolvida no mecanismo que regulam vários processos metabólicos, entre os quais os envolvidos na expressão de proteínas e neste estudo os que estão envolvidos no metabolismo do colesterol, que poderia explicar fenótipos hipercolesterolemicos sem demonstração clara de variantes nos genes de consenso. O objetivo do presente estudo foi comparar o perfil de metilação dos genes LDLR, PCSK9 e LDLRAP1 entre pacientes com diagnóstico de Hipercolesterolemia Familial confirmado através de variantes genéticas descritas na literatura e pacientes sem diagnóstico confirmado. Além da comparação com indíviduos normolipidêmicos. A seleção dos indivíduos foi realizada na Seção de Dislipidemia do Instituto Dante Pazzanese de Cardiologia (IDPC), do Departamento de Análises Clínicas e Toxicológicas da Universidade Federal do Rio Grande do Norte (UFRN), da Universidade Estadual de Campinas (UNICAMP) e da Faculdade de Medicina de São José do Rio Preto (FAMERP). Através dos critérios MEDPED foram selecionados 133 pacientes para a realização do sequenciamento de um painel de genes relacionados ao fenótipo de HF e a homeostasia do colesterol a fim de confirmar o diagnóstico. Todos os pacientes tiveram o DNA purificado, que foi submetido ao tratamento com bissulfito, amplificado, purificado, desnaturado e sequenciado no sistema PyroMark Q24. Avaliou-se o perfil de metilação, em sítio CpG dos genes da LDLR, PCSK9 e LDLR AP1. A análise estatística foi realizada utilizando o software SPSS v.19, GraphPad Prism, versão 1.03 e o e o software R. 4.1.0. Os pacientes foram classificados em Grupo I: Pacientes com diagnóstico molecular confirmado pelo estudo fenotípico e genotipico (n=40); Grupo II: Pacientes fenotipicamente determinados como hipercolesterolemico, mas sem diagnóstico molecular confirmado pelo estudo genomico (n=93); Grupo III: indivíduos fenotipicamente determinados normolipidêmicos de acordo com a V Diretriz Brasileira de Dislipidemia (n=23). A análise comparativa entre os grupos I x II e II x III, demonstrou diferença estatísta significativa em 13 sítios CpG do total de 28 sítios CpG analisados nos três genes. Além disso, foi possível concluir que alterações nos sítios CpG presentes no gene LDLR influenciaram na presença de xantomas e arco córneo. Houve correlação positiva entre a idade e perfil de metilação do gene PCSK9, assim como, alterações nos sítios CpG deste gene influenciaram na presença de arco córneo e IAM. Além disso, alterações no sítio CPG presente no gene LDLRAP1 influenciou no desenvolvimento de DAC, IAM e RM, além da presença de xantelasma

The genotypic variabilities that determine some phenotypic and metabolic alterations can be misdiagnosed if based only on genomic data. In familial hypercholesterolemia (FH) it can be observed that the data of variants in the genes of LDLR, PCSK9, APOB and LDLR AP1 suggested by the current consensus to confirm the diagnosis, has shown to be insufficient, showing a low percentage of confirmation, even in the cases in which phenotypic characteristics present important suggestive data. Complementing the diagnostic aid with epigenetic data has been suggested in many diseases, especially in chronic degenerative diseases. DNA methylation may be involved in the mechanisms that regulate several metabolic processes, including those involved in the expression of proteins that ,in this study, are involved in cholesterol metabolism, which could explain hypercholesterolemic phenotypes without a clear demonstration of variants in consensus genes. The aim of the present study was to compare the methylation profile of LDLR, PCSK9 and LDLRAP1 genes between patients with a diagnosis of Familial Hypercholesterolemia confirmed through genetic variants described in the literature and patients without a confirmed diagnosis. In addition to the comparison with normolipidemic individuals. The selection of individuals was carried out at the Dyslipidemia Section of the Instituto Dante Pazzanese de Cardiologia (IDPC), in the Department of Clinical and Toxicological Analyzes of the Federal University of Rio Grande do Norte (UFRN), in the State University of Campinas (UNICAMP) and in the Faculdade of Medicine of São José do Rio Preto (FAMERP). Through the MEDPED criteria, 133 patients were selected to perform the sequencing of a panel of genes related to the FH phenotype and cholesterol homeostasis in order to confirm the diagnosis. All patients had their DNA purified, which were subjected to bisulfite treatment, amplified, purified, denatured and sequenced on the PyroMark Q24 system. The methylation profile in the CpG site of the LDLR, PCSK9 and LDLRAP1 genes were evaluated. Statistical analysis were performed using SPSS v.19 software, GraphPad Prism, version 1.03 and R. 4.1.0 software. Patients were classified into Group I: Patients with a molecular diagnosis confirmed by phenotypic and genotypic studies (n=40); Group II: Patients phenotypically determined to be hypercholesterolemic, but without a molecular diagnosis confirmed by the genomic study (n=93); Group III: phenotypically determined normolipidemic individuals according to the V Brazilian Dyslipidemia Directive (n=23). The comparative analysis between groups I x II and II x III showed a statistically significant difference in 13 CpG sites of the total of 28 CpG sites analyzed in the three genes of the project. Furthermore, it was possible to conclude that alterations in the CpG sites present in the LDLR gene influenced the presence of xanthomas and arc corneum. There was a positive correlation between age and PCSK9 gene methylation profile, as well as changes in the CpG sites of this gene influenced the presence of arc corneum and AMI. In addition, alterations in the site present in the LDLRAP1 gene are influencing the development of CAD, AMI and MR, in addition to the presence of xanthelasma

Prognostic value of CAD-RADS classification by coronary CTA in patients with suspected CAD.

BACKGROUND: The study sought to compare Coronary Artery Disease Reporting and Data System (CAD-RADS) classification with traditional coronary artery disease (CAD) classifications and Duke Prognostic CAD Index for predicting the risk of all-cause mortality in patients with suspected CAD. METHODS: 9625 consecutive suspected CAD patients were assessed by coronary CTA for CAD-RADS classification, traditional CAD classifications and Duke Prognostic CAD Index. Kaplan-Meier and multivariable Cox models were used to estimate all-cause mortality. Discriminatory ability of classifications was assessed using time dependent receiver-operating characteristic (ROC) curves and The Hosmer-Lemeshow goodness-of-fit test was employed to evaluate calibration. RESULTS: A total of 540 patients died from all causes with a median follow-up of 4.3 ± 2.1 years. Kaplan-Meier survival curves showed the cumulative events increased significantly associated with CAD-RADS, three traditional CAD classifications and Duke Prognostic CAD Index. In multivariate Cox regressions, the risk for the all-cause death increased from HR 0.861 (95% CI 0.420-1.764) for CAD-RADS 1 to HR 2.761 (95% CI 1.961-3.887) for CAD-RADS 4B&5, using CAD-RADS 0 as the reference group. The relative HRs for all-cause death increased proportionally with the grades of the three traditional CAD classifications and Duke Prognostic CAD Index. The area under the time dependent ROC curve for prediction of all-cause death was 0.7917, 0.7805, 0.7991for CAD-RADS in 1 year, 3 year, 5 year, respectively, which was non-inferior to the traditional CAD classifications and Duke Prognostic CAD Index. CONCLUSIONS: The CAD-RADS classification provided important prognostic information for patients with suspected CAD with noninvasive evaluation, which was non-inferior than Duke Prognostic CAD Index and traditional stenosis-based grading schemes in prognostic value of all-cause mortality. Traditional and simplest CAD classification should be preferable, given the more number of groups and complexity of CAD-RADS and Duke prognostic index, without using more time consuming classification.

A meta-analysis of randomized controlled trials comparing percutaneous coronary intervention with optimal medical therapy in stable obstructive coronary artery disease.

BACKGROUND: The optimal treatment for patients suffering from stable obstructive coronary artery disease (SOCAD) is controversial. Many studies have examined the value of performing percutaneous coronary intervention (PCI) in these patients but so far no study has been able to demonstrate an improvement in outcomes by performing PCI in addition to optimal medical therapy (OMT). This study aimed to examine the added value of performing PCI plus OMT vs. OMT alone regarding cardiovascular outcomes. METHODS AND RESULTS: We performed a systematic search and a meta-analysis for randomized controlled trials comparing PCI plus OMT vs. OMT in SOCAD patients. We included six trials (N = 11 144) with follow-up ranges 2.2-11.4 years. The pooled analysis showed no significant difference between PCI + OMT vs. OMT group regarding all-cause mortality, odds ratio (OR) = 0.98 [confidence interval (CI) 0.86-1.12, P = 0.79, I2 = 0%]. In addition, we have found no difference between the two groups regarding cardiovascular mortality, OR = 0.91 (CI 0.76-1.08, P = 0.27, I2 = 24%). Moreover, there was no difference in the incidence of myocardial infarction, OR = 0.92 (CI 0.81-1.04, P = 0.18, I2 = 49%). CONCLUSION: Our results suggest that there is no improvement in cardiovascular outcomes of patients with SOCAD by performing PCI plus OMT vs. OMT alone. This study provides an insight that should be taken under consideration in the management of SOCAD patients.

The additive prognostic value of coronary calcium score (CCS) to single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI)-real world data from a single center.

AIMS: Single-photon emission computed tomography myocardial perfusion imaging [SPECT-MPI] is a functional test for coronary ischemia. We aimed to assess the additive prognostic value of coronary calcium score (CCS) to SPECT-MPI in stable patients. METHODS: This study is a retrospective analysis of 655 patients who underwent SPECT-MPI with CCS (2012 to 2017). Receiver operator characteristic (ROC) identified CCS cutoff value for all-cause mortality: CCS+ if > cutoff value and MPI+ if ≥ 5% total perfusion defect (TPD). Patients were divided into 1 MPI-/CCS-; 2 MPI+/CCS-; 3 MPI-/CCS+; 4 MPI+/CCS+ and compared. Cox proportional hazard analysis identified predictors of mortality. RESULTS: CCS cutoff for all-cause mortality was > 216 (C statistic 0.756, P < 0.0001). In MPI+ groups, mean TPD was similar (13.4% and 13.1% respectively) but mortality was higher in the CCS+ (12.5% vs. 4.8%, P = 0.22) as was the severe LV systolic dysfunction (8.0% vs. 0%, P = 0.095). In MPI- groups, mean TPD was similar (0.7% and 0.9% respectively) but all-cause mortality was higher in the CCS+ (10.7% vs. 1.6%, P < 0.0001) as was severe LVSD (2.9 % vs. 0.3% P = 0.016). Age, smoking, renal impairment ,and CCS > 216 were independent predictors of mortality. CONCLUSIONS: Patients with raised CCS on SPECT-MPI have increased mortality and poor LV function despite a negative MPI.

[Chronic coronary syndrome : New classification of stable coronary artery disease]. / Chronisches Koronarsyndrom : Neuklassifikation der stabilen koronaren Herzkrankheit.

In 2019 the European Society for Cardiology (ESC) published guidelines for the diagnosis and management of chronic coronary syndromes (CCS). Thus the term "stable coronary artery disease" is replaced by CCS. The newly introduced term is based on the current understanding of pathogenesis and clinical features of coronary artery disease (CAD) as well as therapeutic management. CCS defines CAD as a chronic process that can be influenced by lifestyle adjustments, pharmacological therapies and invasive interventions (percutaneous coronary intervention, coronary artery bypass grafting) with the aim of stabilization or regression. The present work provides an overview of various scenarios that involve CCS and diagnostic pathways to clarify potentially relevant CAD. It also highlights therapeutic management and secondary preventive procedures in accordance with the current recommendations of the ESC.

Impact of Training Based on Orem's Theory on Self-Care Agency and Quality of Life in Patients With Coronary Artery Disease.

BACKGROUND: Coronary artery disease (CAD) is a primary cause of death worldwide. CAD negatively affects individuals because it reduces their functional skills and self-care abilities and disrupts quality of life. PURPOSE: This study was designed to assess the impact of a training program based on Orem's self-care deficit nursing theory (SCDNT) on self-care abilities and quality of life in patients with CAD. METHODS: This study was conducted using a randomized, controlled, pretest/posttest experimental design. One hundred two patients with CAD were divided evenly into either the intervention or control group, with sample randomization based on gender, age, low-density lipoprotein cholesterol level, and Self-Care Agency Scale scores. For both groups, interviews were conducted in two sessions held, respectively, at the hospital and at home. Study data were collected using the patient information form, Self-Care Agency Scale, MacNew Heart Disease Health-Related Quality of Life Questionnaire (MacNew), Quality of Life Questionnaire (15D), and training booklet. RESULTS: A highly significant difference was found between the two groups in terms of the average posttest scores on the Self-Care Agency Scale, MacNew, and 15D. For the intervention group, the posttest scores on the Self-Care Agency Scale, MacNew, and 15D were significantly higher than the pretest scores, whereas average pretest and posttest scores on these measures were similar for the control group. CONCLUSIONS: The training program developed in this study based on Orem's SCDNT improved self-care agency as well as disease-specific and overall quality of life in patients with CAD. Nurses should pay attention to the CAD-related educational level of patients when teaching them how to live with their disease. Moreover, nurses should use Orem's SCDNT to strengthen the self-care agency of these patients to increase quality of life and the effectiveness of related education efforts. Finally, medical institutions and governments should develop appropriate education policies for patients at risk of CAD and for those with CAD.

Association of Cardiovascular Disease Risk Factor Burden With Progression of Coronary Atherosclerosis Assessed by Serial Coronary Computed Tomographic Angiography.

Importance: Several studies have reported that the progression of coronary atherosclerosis, as measured by serial coronary computed tomographic (CT) angiography, is associated with the risk of future cardiovascular events. However, the cumulative consequences of multiple risk factors for plaque progression and the development of adverse plaque characteristics have not been well characterized. Objectives: To examine the association of cardiovascular risk factor burden, as assessed by atherosclerotic cardiovascular disease (ASCVD) risk score, with the progression of coronary atherosclerosis and the development of adverse plaque characteristics. Design, Setting, and Participants: This cohort study is a subgroup analysis of participant data from the prospective observational Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) study, which evaluated the association between serial coronary CT angiography findings and clinical presentation. The PARADIGM international multicenter registry, which includes 13 centers in 7 countries (Brazil, Canada, Germany, Italy, Portugal, South Korea, and the US), was used to identify 1005 adult patients without known coronary artery disease who underwent serial coronary CT angiography scans (median interscan interval, 3.3 years; interquartile range [IQR], 2.6-4.8 years) between December 24, 2003, and December 16, 2015. Based on the 10-year ASCVD risk score, the cardiovascular risk factor burden was classified as low (<7.5%), intermediate (7.5%-20.0%), or high (>20.0%). Data were analyzed from February 8, 2019, to April 17, 2020. Exposures: Association of baseline ASCVD risk burden with plaque progression. Main Outcomes and Measures: Noncalcified plaque, calcified plaque, and total plaque volumes (mm3) were measured. Noncalcified plaque was subclassified using predefined Hounsfield unit thresholds for fibrous, fibrofatty, and low-attenuation plaque. The percent atheroma volume (PAV) was defined as plaque volume divided by vessel volume. Adverse plaque characteristics were defined as the presence of positive remodeling, low-attenuation plaque, or spotty calcification. Results: In total, 1005 patients (mean [SD] age, 60 [8] years; 575 men [57.2%]) were included in the analysis. Of those, 463 patients (46.1%) had a low 10-year ASCVD risk score (low-risk group), 373 patients (37.1%) had an intermediate ASCVD risk score (intermediate-risk group), and 169 patients (16.8%) had a high ASCVD risk score (high-risk group). The annualized progression rate of PAV for total plaque, calcified plaque, and noncalcified plaque was associated with increasing ASCVD risk (r = 0.26 for total plaque, r = 0.23 for calcified plaque, and r = 0.11 for noncalcified plaque; P < .001). The annualized PAV progression of total plaque, calcified plaque, and noncalcified plaque was significantly greater in the high-risk group compared with the low-risk and intermediate-risk groups (for total plaque, 0.99% vs 0.45% and 0.58%, respectively; P < .001; for calcified plaque, 0.61% vs 0.23% and 0.36%; P < .001; and for noncalcified plaque, 0.38%vs 0.22% and 0.23%; P = .01). When further subclassified by noncalcified plaque type, the annualized PAV progression of fibrofatty and low-attenuation plaque was greater in the high-risk group (0.09% and 0.02%, respectively) compared with the low- to intermediate-risk group (n = 836; 0.02% [P = .02] and 0.001% [P = .008], respectively). The interval development of adverse plaque characteristics was greater in the high-risk group compared with the low-risk and intermediate-risk groups (for new positive remodeling, 73 patients [43.2%] vs 151 patients [32.6%] and 133 patients [35.7%], respectively; P = .02; for new low-attenuation plaque, 26 patients [15.4%] vs 44 patients [9.5%] and 35 patients [9.4%]; P = .02; and for new spotty calcification, 37 patients [21.9%] vs 52 patients [11.2%] and 54 patients [14.5%]; P = .002). The progression of noncalcified plaque subclasses and the interval development of adverse plaque characteristics did not significantly differ between the low-risk and intermediate-risk groups. Conclusions and Relevance: Progression of coronary atherosclerosis occurred across all ASCVD risk groups and was associated with an increase in 10-year ASCVD risk. The progression of fibrofatty and low-attenuation plaques and the development of adverse plaque characteristics was greater in patients with a high risk of ASCVD.

CAD-RADS: Pushing the Limits.

Coronary CT angiography is now established as the first-line diagnostic imaging test to exclude coronary artery disease (CAD) in the population at low to intermediate risk. Wide variability exists in both the reporting of coronary CT angiography and the interpretation of these reports by referring physicians. The CAD Reporting and Data System (CAD-RADS) is sponsored by multiple societies and is a collaborative effort to provide standard classification of CAD, which is then integrated into patient clinical care. The main goals of the CAD-RADS are to decrease variability among readers; enhance communication between interpreting and referring clinicians, allowing collaborative determination of the best course of patient care; and generate consistent data for auditing, data mining, quality improvement, research, and education. There are several scenarios in which the CAD-RADS guidelines are ambiguous or do not provide definite recommendations for further management of CAD. The authors discuss the CAD-RADS categories and modifiers, highlight a variety of complex or ambiguous scenarios, and provide recommendations for managing these scenarios. Online supplemental material is available for this article. ©RSNA, 2020 See discussion on this article by Aviram and Wolak.

Performance of a deep learning algorithm for the evaluation of CAD-RADS classification with CCTA.

BACKGROUND AND AIMS: Artificial intelligence (AI) is increasing its role in diagnosis of patients with suspicious coronary artery disease. The aim of this manuscript is to develop a deep convolutional neural network (CNN) to classify coronary computed tomography angiography (CCTA) in the correct Coronary Artery Disease Reporting and Data System (CAD-RADS) category. METHODS: Two hundred eighty eight patients who underwent clinically indicated CCTA were included in this single-center retrospective study. The CCTAs were stratified by CAD-RADS scores by expert readers and considered as reference standard. A deep CNN was designed and tested on the CCTA dataset and compared to on-site reading. The deep CNN analyzed the diagnostic accuracy of the following three Models based on CAD-RADS classification: Model A (CAD-RADS 0 vs CAD-RADS 1-2 vs CAD-RADS 3,4,5), Model 1 (CAD-RADS 0 vs CAD-RADS>0), Model 2 (CAD-RADS 0-2 vs CAD-RADS 3-5). Time of analysis for both physicians and CNN were recorded. RESULTS: Model A showed a sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 47%, 74%, 77%, 46% and 60%, respectively. Model 1 showed a sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 66%, 91%, 92%, 63%, 86%, respectively. Conversely, Model 2 demonstrated the following sensitivity, specificity, negative predictive value, positive predictive value and accuracy: 82%, 58%, 74%, 69%, 71%, respectively. Time of analysis was significantly lower using CNN as compared to on-site reading (530.5 ± 179.1 vs 104.3 ± 1.4 sec, p=0.01) CONCLUSIONS: Deep CNN yielded accurate automated classification of patients with CAD-RADS.

Association between cardiovascular risk factors and coronary artery disease assessed using CAD-RADS classification: a cross-sectional study in Romanian population.

OBJECTIVES: This study aimed to evaluate the association between cardiovascular risk factors and Coronary Artery Disease-Reporting and Data System (CAD-RADS) score in the Romanian population. CAD-RADS is a new, standardised method to assess coronary artery disease (CAD) using coronary CT angiography (CCTA). DESIGN: A cross-sectional observational, patient-based study. SETTING: Referred imaging centre for CAD in Transylvania, Romania. PARTICIPANTS: We retrospectively reviewed 674 patients who underwent CCTA between January 2017 and August 2018. The exclusion criteria included: previously known CAD, defined as prior myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft surgery (n=91), cardiac CT for other than evaluation of possible CAD (n=85), significant arrhythmias compromising imaging quality (n=23). Finally, 475 patients fulfilled the inclusion criteria. METHODS: Demographical, clinical and CCTA characteristics of the patients were obtained. CAD was evaluated using CAD-RADS score. Obstructive CAD was defined as ≥50% stenosis of ≥1 coronary segment on CCTA. RESULTS: We evaluated the association between risk factors and CAD-RADS score in univariate and multivariable analysis. We divided the patients into two groups according to the CAD-RADS system: group 1: CAD-RADS score between 0 and 2 (stenosis <50%) and group 2: CAD-RADS score ≥3 (stenosis ≥50%). On univariate analysis, male gender, age, hypertension, dyslipidaemia, smoking and diabetes mellitus were positively associated with a CAD-RADS score ≥3. The multivariate analysis showed that male sex, age, dyslipidaemia, hypertension and smoking were independently associated with obstructive CAD. CONCLUSION: This study demonstrated a significant association between multiple cardiovascular risk factors and a higher coronary atherosclerotic burden assessed using CAD-RADS system in the Romanian population.

Fallacies and Possible Remedies of the SYNTAX Score.

Quite a few studies have revealed the clinical values regarding the outcome predictions in the cohort of the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial and decision-making with the SYNTAX score. The Evaluation of Xience Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left-Main Revascularization (EXCEL) and Nordic-Baltic-British left main revascularization (NOBLE) studies are the largest international randomized studies so far, comparing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) in the treatment of left main coronary artery disease. Unfortunately, both studies failed to validate the value of the SYNTAX score in the selection of revascularization strategies for patients with coronary artery diseases (CAD).. This scenario prompted us to reconsider the inherent fallacies of the SYNTAX score in its derivation. We pointed out eight fallacies for the SYNTAX score in this paper. A recently developed Coronary Artery Tree description and Lesion EvaluaTion (CatLet) score, available at http://www.catletscore.com, a novel angiographic scoring system, could be the remedies for the SYNTAX score.

Prognostic significance of the Medina classification in bifurcation lesion percutaneous coronary intervention with second-generation drug-eluting stents.

The Medina classification is the most widespread method to describe bifurcation lesions. However, little is known regarding its prognostic impact. Therefore, the aim of this study is to assess the prognostic significance of the Medina classification following percutaneous coronary intervention (PCI). From a prospective registry of 738 consecutive patients undergoing PCI for bifurcation lesions, 505 were treated with second-generation drug-eluting stents (DES). Of these, 407 (80.6%) presented with "true bifurcation" (TB) lesions (Medina class 1.0.1, 1.1.1, 0.1.1) and 98 (19.4%) in all other categories ("non-true bifurcation" = NTB). We compared rates of death and major adverse cardiac events (MACE: cardiac death, myocardial infarction, or target vessel revascularization) at 12 months and 3 years. Patients with TB had lower rates of previous bypass surgery (7.4% vs. 11.2%, p = 0.043). TB lesions were more likely to be calcified (33.9% vs. 28.6%, p = 0.003) and ulcerated (8.8% vs. 4.1%, p < 0.01). At 12 months, mortality was numerically higher for TB PCI (4.1% vs. 2.1%, p = 0.052) and MACE rates were higher (19.2% vs. 10.2%, p < 0.001). At 3 years, both all-cause death (10.1% vs. 5.1%, p = 0.002) and rates of MACE (37.2% vs. 17.6%, p < 0.001) were higher for TB PCI. After performing regression analysis, TB remained an independent predictor for poor outcomes (OR-2.28 at 12 months, CI 1.45-9.50, p = 0.007, OR-3.75 at 3 years, CI 1.52-6.77, p = 0.001 for MACE). In conclusion, TB lesions, according to the Medina classification, portend worse prognosis for patients undergoing bifurcation PCI. This may guide prognostication and decision-making in treatment.

Comparative effectiveness analysis of percutaneous coronary intervention versus coronary artery bypass grafting in patients with chronic kidney disease and unprotected left main coronary artery disease.

AIMS: Outcomes according to the status of renal insufficiency have not been fully evaluated in left main coronary artery disease (LMCAD). In the present study therefore, we sought to evaluate clinical outcomes in patients with significant LMCAD stratified by the degree of renal insufficiency and the relative clinical outcomes after PCI and CABG stratified by the differential levels of renal function using data from the large multinational "all-comers" Interventional Research Incorporation Society-Left MAIN Revascularization (IRIS-MAIN) registry. METHODS AND RESULTS: Among 4,894 patients with LMCAD, renal insufficiency was graded according to the estimated glomerular filtration rate (eGFR). The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as death, myocardial infarction, stroke, or any revascularisation. The patients were stratified into three groups according to eGFR: 3,824 (78%) in group 1 (eGFR ≥60 ml·min-1·1.73 m2), 838 (17%) in group 2 (eGFR ≥30 and <60), and 232 (5%) in group 3 (eGFR <30). At two years, after adjustment, compared with group 1, the risk of MACCE was significantly higher in group 2 (hazard ratio [HR] 1.46, 95% confidence interval [CI]: 1.18-1.79) and in group 3 (HR 3.39, 95% CI: 2.61-4.40). The p interaction for MACCE across groups was 0.20. The adjusted risk of MACCE was similar between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in groups 1 and 2. However, PCI was associated with a significantly higher risk of MACCE compared to CABG (HR 1.88, 95% CI: 1.08-3.25) in group 3. CONCLUSIONS: The degree of renal insufficiency was proportionately associated with unfavourable outcomes in patients with LMCAD. In group 3, PCI was associated with a higher risk of MACCE compared with CABG. Also, the effect of PCI versus CABG on MACCE was consistent, with PCI being associated with less bleeding and CABG being associated with less repeat revascularisation.

The myth of 'stable' coronary artery disease.

Patients with known cardiovascular disease who have not had a recent acute event are often referred to as having stable coronary artery disease (CAD). The concept of 'stable' CAD is misleading for two important reasons: the continuing risks of cardiovascular events over the longer term and the diverse spectrum of powerful risk characteristics. The risks of cardiovascular events are frequently underestimated and continue to exist, despite current standards of care for secondary prevention, including lifestyle changes, optimal medical therapy, myocardial revascularization and the use of antiplatelet agents to limit thrombosis. In dispelling the myth of 'stable' CAD, we explore the pathophysiology of the disease and the relative contribution of plaque and systemic factors to cardiovascular events. A broader concept of the vulnerable patient, not just the vulnerable plaque, takes into account the diversity and future risks of atherothrombotic events. We also evaluate new and ongoing research into medical therapies aimed at further reducing the risks of cardiovascular events in patients with chronic - but not stable - atherothrombotic disease.

Coronary artery disease risk reclassification using an acoustic-based score in view of the new European Society of Cardiology 2019 guidelines on Chronic Coronary Syndromes.

In August 2019, ESC published new guidelines on Chronic Coronary Syndromes including a new risk assessment paradigm for estimation of pre-test-probability. The CAD-score is an acoustic-based score for ruling-out of coronary artery disease (CAD). In the current letter to the editor we re-evaluate the re-classification potential the CAD-score in the view of the new guidelines.

A noninvasive and highly sensitive approach for the assessment of coronary collateral circulation by 192-slice third-generation dual-source computed tomography.

The coronary collateral circulation (CCC) is an alternative source of blood supply when the original vessels fail to provide sufficient blood. The accurate detection of CCC is critical for the treatment of ischemic heart disease, especially when the stent surgery is not an option. The assessment of minute vessels such as coronary collateral arteries is challenging. The objective of this study was to assess the feasibility of detection and classification of CCC using the192-slice third-generation dual-source computed tomography angiography (192-slice DSCT CTA).Eight hundred patients (450 men and 350 women, mean age: 56 ±â€Š11 years) with complete or subtotal occlusion of at least 1 major coronary artery were enrolled for our study. February 2016 and September 2018, the patient both 192-slice DSCT CTA and conventional coronary angiography (CAG) were performed in all enrolled patients. The interval between two approaches for a given patient was 6.1 ±â€Š3.7 days (Range: 1-15). The diagnostic accuracy of 192-slice DSCT CTA was evaluated by comparing it with that of CAG. The identified CCC was graded according to the Rentrop classification.The prevalence among patients of having at least 1 CCC was 43.8%. The sensitivity for detecting CCC by 192-slice DSCT was 91.7% (95% CI: 88.3% to 94.3%), specificity was 95.5% (95% CI: 93.1% to 97.2%), positive predictive value was 94.3% (95% CI: 91.5% to 96.2%), and negative predictive value was 93.3% (95% CI: 90.9% to 95.3%). Cohen-Kappa analysis showed that the consistency of the correct classification of CCC using CAG and 192-slice DSCT was very high with the kappa coefficient (κ) of 0.94 (95% CI: 0.91-0.96, P value = .01). Additionally, the radiation dose for 192-slice DSCT was as low as 0.42 ±â€Š0.04 mSv (range, 0.35-0.43 mSv).The 192-slice DSCT CTA is a reliable and sensitive non-invasive method for the evaluation of CCC with low radiation doses.

Automated plaque classification using computed tomography angiography and Gabor transformations.

Cardiovascular diseases are the primary cause of death globally. These are often associated with atherosclerosis. This inflammation process triggers important variations in the coronary arteries (CA) and can lead to coronary artery disease (CAD). The presence of CA calcification (CAC) has recently been shown to be a strong predictor of CAD. In this clinical setting, computed tomography angiography (CTA) has begun to play a crucial role as a non-intrusive imaging method to characterize and study CA plaques. Herein, we describe an automated algorithm to classify plaque as either normal, calcified, or non-calcified using 2646 CTA images acquired from 73 patients. The automated technique is based on various features that are extracted from the Gabor transform of the acquired CTA images. Specifically, seven features are extracted from the Gabor coefficients : energy, and Kapur, Max, Rényi, Shannon, Vajda, and Yager entropies. The features were then ordered based on the F-value and input to numerous classification methods to achieve the best classification accuracy with the least number of features. Moreover, two well-known feature reduction techniques were employed, and the features acquired were also ranked according to F-value and input to several classifiers. The best classification results were obtained using all computed features without the employment of feature reduction, using a probabilistic neural network. An accuracy, positive predictive value, sensitivity, and specificity of 89.09%, 91.70%, 91.83% and 83.70% was obtained, respectively. Based on these results, it is evident that the technique can be helpful in the automated classification of plaques present in CTA images, and may become an important tool to reduce procedural costs and patient radiation dose. This could also aid clinicians in plaque diagnostics.