High-risk Coronary Artery Disease Patients Research Articles

Ultra-high-resolution CT vs. invasive angiography for detecting hemodynamically significant coronary artery disease: Rationale and methods of the CORE-PRECISION multicenter study

BackgroundDirect coronary arterial evaluation via computed tomography (CT) angiography is the most accurate noninvasive test for the diagnosis of coronary artery disease (CAD). However, diagnostic accuracy is limited in the setting of severe coronary calcification or stents. Ultra-high-resolution CT (UHR-CT) may overcome this limitation, but no rigorous study has tested this hypothesis. MethodsThe CORE-PRECISION is an international, multicenter, prospective diagnostic accuracy study testing the non-inferiority of UHR-CT compared to invasive coronary angiography (ICA) for identifying patients with hemodynamically significant CAD. The study will enroll 150 patients with history of CAD, defined as prior documentation of lumen obstruction, stenting, or a calcium score ≥400, who will undergo UHR-CT before clinically prompted ICA. Assessment of hemodynamically significant CAD by UHR-CT and ICA will follow clinical standards. The reference standard will be the quantitative flow ratio (QFR) with <0.8 defined as abnormal. All data will be analyzed in independent core laboratories. ResultsThe primary outcome will be the comparative diagnostic accuracy of UHR-CT vs. ICA for detecting hemodynamically significant CAD on a patient level. Secondary analyses will focus on vessel level diagnostic accuracy, quantitative stenosis analysis, automated contour detection, in-depth plaque analysis, and others. ConclusionCORE-PRECISION aims to investigate if UHR-CT is non-inferior to ICA for detecting hemodynamically significant CAD in high-risk patients, including those with severe coronary calcification or stents. We anticipate this study to provide valuable insights into the utility of UHR-CT in this challenging population and for its potential to establish a new standard for CAD assessment.

Haplotype of the Lipoprotein(a) Gene Variants rs10455872 and rs3798220 Is Associated with Parameters of Coagulation, Fibrinolysis, and Inflammation in Patients after Myocardial Infarction and Highly Elevated Lipoprotein(a) Values.

Lipoprotein(a) (Lp(a)) is an independent risk factor for future coronary events. Variants rs10455872 and rs3798220 in the gene encoding Lp(a) are associated with an increased Lp(a) concentration and risk of coronary artery disease. We aimed to determine whether in high-risk coronary artery disease patients these two genetic variants and the kringle IV type 2 (KIV-2) repeats are associated with impairment of inflammatory and hemostatic parameters. Patients after myocardial infarction with elevated Lp(a) levels were included. Blood samples underwent biochemical and genetic analyses. In carriers of the AC haplotype, the concentrations of tumor necrosis factor (TNF)-α (4.46 vs. 3.91 ng/L, p = 0.046) and plasminogen activator inhibitor-1 (PAI-1) (p = 0.026) were significantly higher compared to non-carriers. The number of KIV-2 repeats was significantly associated with the concentration of high-sensitivity C-reactive protein (ρ = 0.251, p = 0.038) and overall fibrinolytic potential (r = -0.253, p = 0.038). In our patients, a direct association between the AC haplotype and both TNF-α and PAI-1 levels was observed. Our study shows that the number of KIV-2 repeats not only affects proatherosclerotic and proinflammatory effects of Lp(a) but is also associated with its antifibrinolytic properties.

Carotid Artery Ultrasonography as a Screening Tool for Predicting Coronary Artery Disease: A Cross-sectional Study from Hilly State of Northern India

Introduction: Coronary Artery Disease (CAD) is a major cause of morbidity and mortality worldwide; therefore, early diagnosis plays a crucial role in managing patients with CAD. Multidetector Computed Tomography (MDCT) allows non invasive visualisation of coronary arteries but has limited availability, involves radiation, and is costly. Carotid artery atherosclerosis can be assessed by Ultrasound (USG) in terms of Carotid Intima-media Thickness (CIMT) and carotid plaque assessment. These carotid USG parameters are associated with CAD and can be used to predict CAD in high-risk patients. Aim: To study the association and correlation between carotid artery atherosclerosis USG parameters (CIMT and carotid plaque) and CAD, using Computed Tomography Coronary Angiography (CTCA) as a reference. Materials and Methods: A cross-sectional study was conducted from January 2020 to October 2021 in the Department of Radiodiagnosis at Indira Gandhi Medical College, Shimla, Himachal Pradesh, India. In the present study, 31 patients with suspected CAD were enrolled. All patients underwent CTCA followed by carotid artery USG within two weeks. The association and correlation between carotid artery atherosclerosis on USG and CAD on CTCA were examined. Sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), and accuracy were calculated using CTCA as the reference standard. Categorical data were analysed using the Chi-square test, with a p-value of &lt;0.05 considered statistically significant. Results: The mean age of the patients was 54.06±10.79 years. The CAD was observed in 14 (45.1%) cases, of which 13 (92.8%) had significant CAD. Nine patients had raised CIMT, of which eight had CAD. Raised CIMT and CAD showed a significant association with sensitivity, specificity, PPV, NPV, and accuracy of 57.14%, 94.12%, 88.89%, 72.73%, and 77.42%, respectively. A positive correlation was found between CIMT values and the number of vessels with significant CAD (r= +0.67). A total of 7 patients (22.5%) had the presence of carotid plaque, of which 6 (88.57%) had significant CAD. A significant association was found between CAD and the presence of carotid plaque. Carotid plaque had sensitivity, specificity, PPV, NPV, and accuracy of 50%, 100%, 100%, 70.83%, and 77.42%, respectively, in predicting CAD. A positive correlation was observed between carotid plaque burden and the number of vessels with significant CAD (r= +0.56). Conclusion: There is a significant association between carotid ultrasonography parameters (i.e., CIMT, carotid plaque) and CAD. CIMT is a more sensitive parameter than carotid plaque in predicting CAD. However, carotid plaque is more specific for predicting CAD. Carotid artery ultrasonography can be used as a screening tool for predicting CAD and should be included in the work-up of patients with suspected CAD.

Lipoprotein(a) is associated with recurrent cardiovascular events in patients with coronary artery disease and prediabetes or diabetes.

Elevated lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are both associated with adverse events in high-risk patients with established coronary artery disease (CAD). Currently, the association between Lp(a) levels and recurrent cardiovascular (CV) events (CVEs) remained undetermined in patients with different glucose status. Therefore, this study aimed to investigate the prognostic significance of Lp(a) levels for recurrent CVEs in high-risk CAD patients who suffered from first CVEs according to different glycemic metabolism. We recruited 5257 consecutive patients with prior CVEs and followed up for recurrent CVEs, including CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. Patients were assigned to low, medium, and high groups according to Lp(a) levels and further stratified by glucose status. During a median 37-month follow-up, 225 (4.28%) recurrent CVEs occurred. High Lp(a) was independently associated with recurrent CVEs [adjusted Hazard Ratio (HR), 1.57; 95% confidence interval (CI) 1.12-2.19; P = 0.008]. When participants were classified according to Lp(a) levels and glycemic status, high Lp(a) levels were associated with an increased risk of recurrent CVEs in pre-DM (adjusted HR, 2.96; 95% CI 1.24-7.05; P = 0.014). Meanwhile, medium and high Lp(a) levels were both associated with an increased risk for recurrent CVEs in DM (adjusted HR, 3.09; 95% CI 1.30-7.34; P = 0.010 and adjusted HR, 3.13, 95% CI 1.30-7.53; P = 0.011, respectively). This study demonstrated that elevated Lp(a) levels were associated with an increased recurrent CVE risk in patients with CAD, particularly among those with pre-DM and DM, indicating that Lp(a) may provide incremental value in risk stratification in this population.

The Role of Polymorphism in the Endothelial Homeostasis and Vitamin D Metabolism Genes in the Severity of Coronary Artery Disease.

Coronary artery disease (CAD) remains one of the leading causes of cardiovascular morbidity and mortality worldwide. The maintenance of endothelial homeostasis and vitamin D metabolism play an important role in CAD pathogenesis. This study aimed to determine the association of endothelial homeostasis and vitamin D metabolism gene polymorphism with CAD severity. A total of 224 low-risk patients (SYNTAX score ≤ 31) and 36 high-risk patients (SYNTAX score > 31) were recruited for this study. The serum level of E-, L- and P-selectins; endothelin; eNOS; 25OH; and 1.25-dihydroxy vitamin D was measured using an enzyme-linked immunosorbent assay (ELISA). Polymorphic variants in SELE, SELP, SELPLG, END1, NOS3, VDR and GC were analyzed using a polymerase chain reaction (PCR). We found no differences in the serum levels of the studied markers between high- and low-risk patients. Three polymorphic variants associated with CAD severity were discovered: END1 rs3087459, END1 rs5370 and GC rs2298849 in the log-additive model. Moreover, we discovered a significantly decreased serum level of 1.25-dihydroxy vitamin D in high-risk CAD patients with the A/A-A/G genotypes of the rs2228570 polymorphism of the VDR gene, the A/A genotype of the rs7041 polymorphism of the GC gene and the A/A genotype of the rs2298849 polymorphism of the GC gene.

Off-pump CABG surgery in left main coronary artery disease: a single-center prospective registry.

The treatment of left main (LM) coronary artery disease (CAD) requires complex decision-making. Patients with left main multi-vessel coronary artery disease (LM CAD) have concerns regarding incomplete revascularization and reduced survival with off-pump (OPCAB) when compared with on-pump (ONCAB) coronary bypass surgery. To evaluate outcomes among high-risk LM CAD patients undergoing OPCAB, we performed a registry-based prospective study. We performed 4868 coronary artery bypass graft (CABG) surgeries from Jan 2013 to Jun 2019 with 4662 (95.8%) OPCAB. In OPCAB cohort, we had 1323 patients (28.4%) with significant LM (> 50%) triple vessel CAD. Data regarding clinical features, extent of CAD, operative details, in-hospital outcomes, and 3-year follow-up were obtained. Descriptive statistics are reported. The study cohort (n = 1323) was aged 63 ± 9years with men 88.4%. Tobacco use was in 328 (24.8%), diabetes 598 (45.2%), previous myocardial infarction 463 (35.0%), previous coronary intervention 40 (3.0%), and congestive heart failure in 54 (4.1%). All patients had LM (100.0%) with triple vessel disease in 99.4% (LAD, left anterior descending 100.0%; LCX, left circumflex 99.4%; RCA, right coronary artery 78.7%). Vessels bypassed/patient were 2.7 ± 0.4 with 3.2 ± 0.7 total grafts and 2.1 ± 0.8 venous grafts. In total, 1278 (96.5%) patients received left internal mammary artery (LIMA), 63(4.7%) bilateral internal mammary artery (BIMA), and 74 (5.6%) radial artery grafts. There was no patient with conversion from OPCAB to ONCAB. In-hospital major adverse cardiovascular events (MACE: all-cause deaths, myocardial infarction, and stroke) were in 21 (1.6%). At 3-year follow-up (n = 1041), MACE rates were in 84 (8.1%) and cardiovascular deaths in 28 (2.7%). This study shows that off-pump CABG surgery is safe in patients with LM CAD. There is low in-hospital mortality and MACE and 3-year outcomes are similar to the published data of LM CAD patients who undergo on-pump CABG. The online version contains supplementary material available at 10.1007/s12055-023-01526-3.

Validity and Reliability of Point-of-Care Ultrasound for Detecting Moderate- or High-Grade Carotid Atherosclerosis in an Outpatient Department.

The prevalence of carotid stenosis is considerably higher in asymptomatic individuals with multiple risk factors than in the general population. We investigated the validity and reliability of carotid point-of-care ultrasound (POCUS) for rapid carotid atherosclerosis screening. We prospectively enrolled asymptomatic individuals with carotid risk scores of ≥7 who underwent outpatient carotid POCUS and laboratory carotid sonography. Their simplified carotid plaque scores (sCPSs) and Handa's carotid plaque scores (hCPSs) were compared. Of 60 patients (median age, 81.9 years), 50% were diagnosed as having moderate- or high-grade carotid atherosclerosis. The overestimation and underestimation of outpatient sCPSs were more likely in patients with low and high laboratory-derived sCPSs, respectively. Bland-Altman plots indicated that the mean differences between the participants' outpatients and laboratory sCPSs were within two standard deviations of their laboratory sCPSs. A Spearman's rank correlation coefficient revealed a strong positive linear correlation between outpatient and laboratory sCPSs (r = 0.956, p < 0.001). An intraclass correlation coefficient analysis indicated excellent reliability between the two methods (0.954). Both carotid risk score and sCPS were positively and linearly correlated with laboratory hCPS. Our findings indicate that POCUS has satisfactory agreement, strong correlation, and excellent reliability with laboratory carotid sonography, making it suitable for rapid screening of carotid atherosclerosis in high-risk patients.

B-28 | Management of Clinical Stent-In-Stent Restenosis (SISR) in High Risk Coronary Artery Disease Patients With Percutaneous Coronary Intervention (PCI) Followed by Coronary Intravascular Brachytherapy (IVBT)

In-stent-restenosis (ISR) is seen in 10% of patients with DES and is often treated with a repeat DES placement. Recurrent ISR or SISR has a high repeat failure rates, requiring target vessel revascularization (TVR). A combination of the presence of multiple layers of stents, previous restenosis, and other additional comorbidities make this patient population complex and higher risk. Angioplasty followed by IVBT is one possible treatment option in the high-risk patients. This study reviewed the efficacy and safety of PCI followed by IVBT for coronary artery disease in high-risk patients experiencing SISR. A retrospective study was performed which reviewed 78 patients treated between 2016-2021 with SISR involving a total of 91 vessels. All patients underwent PCI with balloon angioplasty followed by IVBT. These patients received localized IVBT radiation using the Novoste Beta-Cath System using a strontium-90 isotope. Radiation dose was delivered based on the vessel diameter, with vessels ≥ 3.5mm in diameter receiving 23 Gy, while vessels of <3.5mm in diameter received 18.4 Gy. Major adverse cardiac events (MACE) were defined as all-cause death, myocardial infarction (MI), and stroke. All patients in the cohort had 2 previously placed DESs in the target lesion. Of total 91 treatments, 67% and 33% treatments were delivered to the LAD or the RCA and circumflex vessel or the marginal arteries, respectively. One patient had intraprocedural cardiac arrest due to suspected intracoronary thrombosis. All patients were symptomatic pre-IVBT and 44% experienced symptomatic reduction after treatment. MACE after IVBT includes MI in 18%, stroke in 5%, and all-cause death occurred in 16% of patients at a median time of 9.3 months post treatment with median follow-up being 22.8 months. Of total, 77% retained patency of the irradiated lesion, while 23% percent experienced restenosis requiring TVR. Coronary restenosis post-deployment of multiple layers of DES remains an ongoing challenge in current times. PCI followed by balloon angioplasty with IVBT is a safe and efficacious treatment option for high-risk coronary artery disease patients with SISR, who have very few treatment options otherwise.

The association of electronic health literacy with behavioural and psychological coronary artery disease risk factors in patients after percutaneous coronary intervention: a 12-month follow-up study.

Fundamental roadblocks, such as non-use and low electronic health (eHealth) literacy, prevent the implementation of eHealth resources. The aims were to study internet usage for health information and eHealth literacy in patients after percutaneous coronary intervention (PCI). Further, we aimed to evaluate temporal changes and determine whether the use of the internet to find health information and eHealth literacy were associated with coronary artery disease (CAD) risk factors at the index admission and 12-month follow-up of the same population. This prospective longitudinal study recruited 2924 adult patients with internet access treated by PCI in two Nordic countries. Assessments were made at baseline and 12-month follow-up, including a de novo question Have you used the internet to find information about health?, the eHealth literacy scale, and assessment of clinical, behavioural, and psychological CAD risk factors. Regression analyses were used. Patients' use of the internet for health information and their eHealth literacy were moderate at baseline but significantly lower at 12-month follow-up. Non-users of the internet for health information were more often smokers and had a lower burden of anxiety symptoms. Lower eHealth literacy was associated with a higher burden of depression symptoms at baseline and lower physical activity and being a smoker at baseline and at 12-month follow-up. Non-use of the internet and lower eHealth literacy need to be considered when implementing eHealth resources, as they are associated with behavioural and psychological CAD risk factors. eHealth should therefore be designed and implemented with high-risk CAD patients in mind. ClinicalTrials.gov NCT03810612 https://clinicaltrials.gov/ct2/show/NCT03810612.

Heritability and environmental influences on the onset of aortic valve sclerosis: a twin population study

Abstract Background Aortic valve sclerosis (AVSc) is the earliest manifestation of a life-threatening cardiovascular disorder, namely aortic valve stenosis (AS). AVSc is also recognized as a red flag linked to worse cardiovascular outcomes in high-risk coronary artery disease patients. However, the genetic background of AVSc is still unknown. Purpose To examine whether the heritability and environmental contributions play a role in the onset of AVSc using a sample of Italian twins. Methods The present study is based on the classical twin design. Twins, aged 50 to 70 years, already enrolled in the Italian Twin Register, were contacted and invited to undergo a clinical, echocardiographic, and complete carotid artery ultrasound examination at the our Center, between July 2017 and December 2021. The presence of AVSc was recognized as non-uniform thickening with or without spotty calcified areas of the aortic valve leaflets without a significant transvalvular gradient (maximum aortic velocity &amp;lt;2.5 m/s). Twin zygosity was assessed through a questionnaire on physical similarity during childhood, known to be ∼95% accurate. Tetrachoric twin correlations by zygosity were estimated with Mx Software using liability threshold saturated models and incorporating age as a covariate. Liability-threshold structural equation modelling was performed to decompose the phenotypic variance into contributions due to additive genetic (A), common environmental (C), and unique environmental (E) effects. Results A total of 216 adult twins (66 monozygotic, MZ and 42 dizygotic pairs, DZ; mean age 59.9±6.2) were enrolled in the study. The estimated prevalence rate of AVSc in the total sample was 29.2%. As significant sex differences were detected (males 45.2% and females 22.7%, p&amp;lt;0.01), the additional twin analyses were performed as intra-sex analyses. Females showed a greater tetrachoric correlation in MZ twins (r=0.37) compared to DZ twins (r=0.23), suggesting the existence of a genetic influence. Genetic factors, under the best (AE) model, accounted for 38% of the variance in liability to AVSc with the remaining contribution due to unique environmental influences (E = 62%). The contribution of the common environment (C) to the goodness of fit was negligible. The male group was too small for statistical calculation. Conclusion To our knowledge, the present study is the first to document the involvement of genetic factors in the development of AVSc. Our data also warrant further studies to both validate the findings obtained and to better explore the heritability of AVSc. Furthermore, our results provide a first evidence that an echocardiographic screening in individuals with relatives affected by AVSc has a scientific rational basis. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Italian Ministry of Health

Peripheral extracorporeal membrane oxygenation support expands the application of robot-assisted coronary artery bypass.

Robot-assisted coronary artery bypass (RCAB) is typically not offered to higher risk patients with reduced cardiopulmonary function, critical coronary artery disease, and challenging chest wall anatomy. In this study, we report the novel use of nonemergency intraoperative peripheral extracorporeal membrane oxygenation as partial cardiopulmonary support during RCAB for patients who were considered high-risk candidates for conventional CAB and at the same time not eligible for RCAB without cardiopulmonary support. Forty-five high risk patients (mean age, 68years; Society of Thoracic Surgeons score, 6.27%; ejection fraction, 45%) underwent RCAB with nonemergency peripheral extracorporeal membrane oxygenation support for the following indications: inability to tolerate single-lung ventilation (n=17; 38%), low ejection fraction <35% (n=17; 38%), inadequate exposure of internal thoracic artery (n=24; 53%), critical coronary artery disease (n=16; 36%), and hemodynamic instability after anesthesia induction (n=3; 7%). Following robotic internal thoracic artery takedown, all patients had beating heart minimally invasive direct CAB through a 2-inch minithoracotomy. Up to 30days, there were no strokes (0%), myocardial infarctions (0%), or access vessel complications (0%). One noncardiac related mortality (2.2%) was related to hemodialysis access issues in a patient with preexisting end-stage renal disease. One redo-CAB (2.2%) patient required sternotomy to locate the target vessel. Thirty-four (75.6%) patients were extubated within 6hours of surgery. Our results examine the feasibility of using peripheral extracorporeal membrane oxygenation during RCAB for high-risk patients who otherwise had limited options. The use of peripheral extracorporeal membrane oxygenation in RCAB can potentially expand the surgical treatment options in high-risk coronary artery disease patients.

Interleukin-35 Mitigates ox-LDL-Induced Proatherogenic Effects via Modulating miRNAs Associated with Coronary Artery Disease (CAD).

Recent emergence of miRNAs as important regulators of processes involving lesion formation and regression has highlighted miRNAs as potent therapeutic targets for the treatment of atherosclerosis. Few studies have reported the atheroprotective role of IL-35, a novel immunosuppressive and anti-inflammatory cytokine; however, miRNA-dependent regulation underlying the anti-atherosclerotic potential of IL-35 remains elusive. THP-1 macrophages were incubated with human recombinant IL-35 (rIL-35) either in the presence or absence of ox-LDL. qRT-PCR was conducted to validate the expression levels of previously identified miRNAs including miR-197-5p, miR-4442, miR-324-3p, miR-6879-5p, and miR-6069 that were differentially expressed in peripheral blood mononuclear cells of coronary artery disease (CAD) patients vs. controls. Additionally, bioinformatic analysis was performed to predict miRNA-associated targets and their corresponding functional significance in CAD. Exogenous IL-35 significantly decreased the average area of ox-LDL-stimulated macrophages, indicating the inhibitory effect of IL-35 on lipid-laden foam cell formation. Furthermore, rIL-35 treatment alleviated the ox-LDL-mediated atherogenic effects by modulating the expression levels of aforementioned CAD-associated miRNAs in the cultured macrophages. Moreover, functional enrichment analysis of these miRNA-related targets revealed their role in the molecular processes affecting different stages of atheroslerotic plaque development, such as macrophage polarization, T cell suppression, lipoprotein metabolism, foam cell formation, and iNOS-mediated inflammation. Our observations uncover the novel role of IL-35 as an epigenetic modifier as it influences the expression level of miRNAs implicated in the pathogenesis of atherosclerosis. Thus, IL-35 cytokine therapy-mediated miRNA targeting could be an effective therapeutic strategy against the development of early atheromas in asymptomatic high-risk CAD patients.

Control of Low-Density Lipoprotein Cholesterol in Secondary Prevention of Coronary Artery Disease in Real-Life Practice: The DAUSSET Study in French Cardiologists.

Introduction: Patients with established coronary artery disease (CAD) are at very high risk for cardiovascular events. Methods: The DAUSSET study is a national, multicenter, non-interventional study that included very high-risk CAD patients followed by French cardiologists. It aimed to describe real-life clinical practices for low-density lipoprotein (LDL) cholesterol control in the secondary prevention of CAD. Results: A total of 912 patients (mean age, 65.4 years; men, 76.1%; myocardial infarction, 69.4%; first episode, 80.1%) were analyzed. The LDL cholesterol goal was 70 mg/dL in most cases (84.9%). The LDL cholesterol goal <70 mg/dL was achieved in 41.7% of patients. Of the 894 (98.0%) patients who received lipid-lowering therapy, 81.2% had been treated more intensively after the cardiac event, 27.0% had been treated less intensively and 13.1% had been maintained. Participating cardiologists were very satisfied or satisfied with treatment response in 72.6% of patients. Moderate satisfaction or dissatisfaction with lipid-lowering therapy was related to not achieving objectives (100%), treatment inefficacy (53.7%), treatment intolerance (23.4%) and poor adherence (12.3%). Conclusion: These real-world results show that lipid control in very high-risk patients remains insufficient. More than half of the patients did not achieve the LDL cholesterol goal. Prevention of cardiovascular events in these very high-risk patients could be further improved by better education and more intensive lipid-lowering therapy.

Vessel-GAN: Angiographic reconstructions from myocardial CT perfusion with explainable generative adversarial networks

Dynamic CT angiography derived from CT perfusion data can obviate a separate coronary CT angiography and the use of ionizing radiation and contrast agent, thereby enhancing patient safety. However, the image quality of dynamic CT angiography is inferior to standard CT angiography images in many studies. This paper proposes an explainable generative adversarial network named vessel-GAN, which resorts to explainable knowledge-based artificial intelligence to perform image translation with increased trustworthiness. Specifically, we design a loss term to better learn the representations of blood vessels in CT angiography images. The loss term based on expert knowledge guides the generator to focus its training on the important features predicted by the discriminator. Additionally, we propose a generator architecture that effectively fuses spatio-temporal representations and further enhances temporal consistency, thereby improving the quality of the generated CT angiography images. The experiment is conducted on a dataset consisting of 232 patients with suspected coronary artery stenosis. Experimental results show that the PSNR value of vessel-GAN is 28.32 dB, SSIM value is 0.91 and MAE value is 47.36. To validate the effectiveness of the proposed synthesis method, we compare that with other image translation frameworks and GAN-based methods. Compared to other image translation methods, the proposed method vessel-GAN can generate more clearly visible blood vessels from source perfusion images. The CTA images generated by vessel-GAN are closer to the real CTA due to the use of adversarial learning. Compared with other GAN-based methods, vessel-GAN can produce sharper and more homogeneous outputs, including realistic vascular structures. The experiment demonstrates that the explainable generative adversarial network has superior performance for it can better control how models learn. Overall, the CT angiography images generated by vessel-GAN can potentially replace a separate standard CT angiography, allowing the possibility of “one-stop” cardiac examination for high-risk coronary artery disease patients who need assessment of myocardial ischemia.

Clinical utility of readily available novel markers of carotid atherosclerotic burden for reclassification and discrimination of very high cardiovascular risk

Abstract Background Among high cardiovascular (CV) risk patients, there is emerging need to recognize those who will benefit from new treatments targeting residual risk. Readily available modalities providing reclassification value would be clinically useful in this setting. Preliminary data suggest that carotid ultrasonography using plaque burden but not intima-media thickness (IMT) is associated with very high risk. Objectives We aimed to assess the reclassification ability of two markers of carotid atherosclerosis in high-risk patients, reflecting total atherosclerotic burden and the most severe lesion and to compare them with the routinely used carotid indices IMT and number of carotid plaques. Methods In an ongoing registry of patients who visited a cardiovascular protection clinic for cardiovascular risk assessment, we enrolled 735 consecutively recruited patients (mean age 63.1 years, 68.8% male) classified as high or very-high CV risk according to 2019 European Society of Cardiology /European Atherosclerosis Society Guidelines. Sum of carotid wall thickness (sumWT) and maximal wall thickness (maxWT) using high-resolution ultrasonography at baseline were used to assess the total burden and the most severe carotid lesion, respectively. These markers integrate maximum plaque height or maximum IMT if no plaque is present. All patients were followed for a median of 41 months and the primary end-point consisted of CV mortality, acute myocardial infarction or coronary revascularization. Results After adjustment for traditional CV risk factors, maxWT and sumWT were associated with the primary end-point (hazard ratio [HR]=1.73 (95% confidence interval [CI]:1.39 to 2.17) and 1.19 (95% CI 1.10 to 1.30) respectively). Both markers were superior in terms of reclassification and discrimination to identify very high risk over validated CV risk scores including the Heartscore and the SMART score (net reclassification index [NRI]=0.624, p&amp;lt;0.0001, integrated discrimination index [IDI]=0.060, p&amp;lt;0.0001 and difference in the area under the curve (δAUC) = 0.136, p&amp;lt;0.001 for maxWT and NRI=0.497, p&amp;lt;0.0001, IDI=0.046, p&amp;lt;0.0001 and δAUC = 0.128, p&amp;lt;0.001 for sumWT), IMT (NRI=0.502, p&amp;lt;0.0001, IDI= 0.058, p=0.02 for maxWT and NRI=0.559, p&amp;lt;0.0001, IDI=0.051, p=0.016 for sumWT) and the number of carotid plaques (NRI=0.614, p&amp;lt;0.0001, IDI=0.038, p=0.001 for maxWT and NRI=0.292, p=0.019, IDI=0.022, p=0.009 for sumWT). Conclusions The use of two novel cumulative markers of atherosclerotic burden improves risk stratification and discriminates high from very high CV risk. Given that carotid ultrasonography is a readily available modality, its clinical application for risk refinement of high-risk patients to facilitate treatment decisions merits further investigation. Funding Acknowledgement Type of funding sources: None.

Aortic Valve Sclerosis in High-Risk Coronary Artery Disease Patients.

Background: Current knowledge regarding the relationship between aortic valve sclerosis (AVSc), cardiovascular risk factors, and mortality in patients with known coronary artery disease (CAD) is still unclear. The present study aimed at investigating the prevalence of AVSc as well as its association with long-term all-cause mortality in high-risk CAD patients that has never been explored in large cohorts thus far.Methods and Results: In this retrospective and observational cohort study we enrolled high-risk CAD patients, hospitalized at Centro Cardiologico Monzino (CCM), Milan, Italy, between January 2006 and December 2016. The morphology and function of the aortic valve were assessed from the recorded echocardiographic images to evaluate the presence of AVSc, defined as a non-uniform thickening of the aortic leaflets with no consequences on hemodynamics. Data on 5-year all-cause mortality was retrieved from a Regional database. Of the 5,489 patients initially screened, 4,938 (mean age 67 ± 11 years, 3,954 [80%] men) were enrolled in the study. In the overall population, AVSc was detected in 2,138 (43%) patients. Multivariable LASSO regression revealed that age, female gender, diabetes mellitus, previous MI, and left ventricular ejection fraction were independently associated with AVSc. All-cause mortality (adjusted hazard ratio: 1.29, 95%CI: 1.05–1.58) was significantly higher in AVSc than in non-AVSc patients.Conclusions: AVSc is frequently detected in high-risk CAD patients and is associated with long-term mortality. Our findings corroborate the hypothesis that AVSc is an underestimated marker of systemic cardiovascular risk. Thus, AVSc detection may be used to improve long-term risk stratification of high-risk CAD patients.

C5 Variant rs10985126 is Associated with Mortality in Patients with Symptomatic Coronary Artery Disease.

BackgroundComplement component 5a (C5a) is a highly potent anaphylatoxin with a variety of pro-inflammatory effects. C5a contributes to progression of atherosclerosis and inhibition of the receptor (C5aR) might offer a therapeutic strategy in this regard. Single nucleotide polymorphisms (SNPs) of the C5 gene may modify protein expression levels and therefore function of C5a and C5aR. This study aimed to examine associations between clinically relevant C5a SNPs and the prognosis of patients with symptomatic coronary artery disease (CAD). Furthermore, we sought to investigate the influence of C5 SNPs on C5aR platelet surface expression and circulating C5a levels.MethodsC5 variants (rs25681, rs17611, rs17216529, rs12237774, rs41258306, and rs10985126) were analyzed in a consecutive cohort of 833 patients suffering from symptomatic coronary artery disease (CAD). Circulating C5a levels were determined in 116 patients whereas C5aR platelet surface expression was measured in 473 CAD patients. Endpoints included all-cause mortality, myocardial infarction (MI), and ischemic stroke (IS). Homozygous carriers (HC) of the minor allele (rs10985126) showed significantly higher all-cause mortality than major allele carriers. While we could not find significant associations between rs10985126 allele frequency and C5aR platelet surfazl ce expression, significantly elevated levels of circulating C5a were found in HC of the minor allele of the respective genotype. rs17216529 allele frequency correlated with the composite combined endpoint and bleeding events. However, since the number of HC of the minor allele of this genotype was low, we cannot draw a robust conclusion about the observed associations.ConclusionIn this study, we provide evidence for the prognostic relevance of rs10985126 in CAD patients. C5 rs10985126 may serve as a prognostic biomarker for risk stratification in high-risk CAD patients and consequently promote tailored therapies.

Lipid biomarkers in statin users with coronary artery disease annotated by coronary computed tomography angiography

Molecular markers are suggested to improve the diagnostic and prognostic accuracy in patients with coronary artery disease (CAD) beyond current clinical scores based on age, gender, symptoms and traditional risk factors. In this context, plasma lipids are emerging as predictors of both plaque composition and risk of future events. We aim to identify plasma lipid biomarkers associated to CAD indexes of stenosis severity, plaque lipid content and a comprensive score of CAD extent and its risk. We used a simple high performance liquid chromatography-tandem mass spectrometry method to identify 69 plasma lipids in 132 subjects referred to Coronary Computed Tomography Angiography (CCTA) for suspected CAD, all under statin treatment. Patients were stratified in groups using three different CCTA-based annotations: CTA-risk score, lipid plaque prevalence (LPP) ratio and the coronary artery disease-reporting and data system (CAD-RADS). We identified a common set of lipid biomarkers composed of 7 sphingomyelins and 3 phosphatidylethanolamines, which discriminates between high risk CAD patients and controls regardless of the CAD annotations used (CTA score, LPP ratio, or CAD-RADS). These results highlight the potential of circulating lipids as biomarkers of stenosis severity, non calcified plaque composition and overall plaque risk of events.

Low-Density Lipoprotein Cholesterol 4: The Notable Risk Factor of Coronary Artery Disease Development

Background: Coronary artery disease (CAD) is the leading cause of death worldwide, which has a long asymptomatic period of atherosclerosis. Thus, it is crucial to develop efficient strategies or biomarkers to assess the risk of CAD in asymptomatic individuals.Methods: A total of 356 consecutive CAD patients and 164 non-CAD controls diagnosed using coronary angiography were recruited. Blood lipids, other baseline characteristics, and clinical information were investigated in this study. In addition, low-density lipoprotein cholesterol (LDL-C) subfractions were classified and quantified using the Lipoprint system. Based on these data, we performed comprehensive analyses to investigate the risk factors for CAD development and to predict CAD risk.Results: Triglyceride, LDLC-3, LDLC-4, LDLC-5, LDLC-6, and total small and dense LDL-C were significantly higher in the CAD patients than those in the controls, whereas LDLC-1 and high-density lipoprotein cholesterol (HDL-C) had significantly lower levels in the CAD patients. Logistic regression analysis identified male [odds ratio (OR) = 2.875, P < 0.001], older age (OR = 1.018, P = 0.025), BMI (OR = 1.157, P < 0.001), smoking (OR = 4.554, P < 0.001), drinking (OR = 2.128, P < 0.016), hypertension (OR = 4.453, P < 0.001), and diabetes mellitus (OR = 8.776, P < 0.001) as clinical risk factors for CAD development. Among blood lipids, LDLC-3 (OR = 1.565, P < 0.001), LDLC-4 (OR = 3.566, P < 0.001), and LDLC-5 (OR = 6.866, P < 0.001) were identified as risk factors. To predict CAD risk, six machine learning models were constructed. The XGboost model showed the highest AUC score (0.945121), which could distinguish CAD patients from the controls with a high accuracy. LDLC-4 played the most important role in model construction.Conclusions: The established models showed good performance for CAD risk prediction, which can help screen high-risk CAD patients in asymptomatic population, so that further examination and prevention treatment might be taken before any sudden or serious event.

Numbers and phenotype of non-classical CD14dimCD16+ monocytes are predictors of adverse clinical outcome in patients with coronary artery disease and severe SARS-CoV-2 infection.

AimsTo elucidate the prognostic role of monocytes in the immune response of patients with coronary artery disease (CAD) at risk for life-threatening heart and lung injury as major complications of SARS-CoV-2 infection.Methods and ResultsFrom February to April 2020, we prospectively studied a cohort of 96 participants comprising 47 consecutive patients with CAD and acute SARS-CoV-2 infection (CAD+SARS-CoV-2), 19 CAD patients without infections, and 30 healthy controls. Clinical assessment included blood sampling, echocardiography, and electrocardiography within 12 hours of admission. Respiratory failure was stratified by the Horovitz Index (HI) as moderately/severely impaired when HI ≤ 200 mmHg. The clinical endpoint (EP) was defined as HI ≤ 200 mmHg with subsequent mechanical ventilation within a follow-up of 30 days.The numbers of CD14dimCD16+ non-classical monocytes in peripheral blood were remarkably low in CAD+SARS-CoV-2 compared to CAD patients without infection and healthy controls (p < 0.0001). Moreover, these CD14dimCD16 monocytes showed decreased expression of established markers of adhesion, migration, and T cell activation (CD54, CD62L, CX3CR1, CD80, HLA-DR). Decreased numbers of CD14dimCD16+ monocytes were associated with the occurrence of EP. Kaplan-Meier curves illustrate that CAD+SARS-CoV-2 patients with numbers below the median of CD14dimCD16+ monocytes (median 1443 cells/mL) reached EP significantly more often compared to patients with numbers above the median (log-rank 5.03, p = 0.025).ConclusionDecreased numbers of CD14dimCD16+ monocytes are associated with rapidly progressive respiratory failure in CAD+SARS-CoV-2 patients. Intensified risk assessments comprising monocyte sub- and phenotypes may help to identify patients at risk for respiratory failure.Translational PerspectivePatients with coronary artery disease (CAD) are at risk of life-threatening heart and lung injury accelerated by the pro-inflammatory and pro-thrombotic immune response during SARS-CoV-2 infection. We found substantially low numbers of CD14dimCD16+ non-classical monocytes with an altered phenotype suggesting impaired migration behaviour and T cell activation capacity in peripheral blood of SARS-CoV-2 patients with CAD, compared to CAD patients without infection or healthy controls. Decreased numbers of CD14dimCD16+ monocytes predicted rapidly progressive respiratory failure (Horovitz index ≤ 200 mmHg) with subsequent mechanical ventilation. Therefore, early sub- and phenotyping of CD14dimCD16+ monocytes using simple flow cytometry might predict worsening of respiratory failure at an early stage of SARS-CoV-2 infection in high-risk CAD patients, who require an extensive heart failure and anti-thrombotic therapy to improve their clinical outcome.