Coronary Artery Research Articles

Improved quantification of coronary stenosis in patients with high calcium scores using spectral reconstructions in coronary CT angiography

Abstract Background Coronary CT angiography has demonstrated reduced accuracy in patients with high calcium scores due to blooming artifacts, often resulting in overestimated stenosis. Purpose This study aimed to assess the impact of spectral reconstructions on coronary stenosis quantification in patients with high calcium scores (>500), utilizing invasive coronary angiography as the gold standard. Methods Twenty consecutive patients referred for coronary artery disease assessment underwent both coronary CT angiography and invasivecoronary angiography. Conventional 120 kV images, 100 keV virtual monoenergetic images, and iodine-no-water images were reconstructed. Two blinded operators independently reviewed the images. Lesions were qualitatively classified in both CCTA and invasive angiography as stenosis of 1-24%, 25-49%, 50-70%, and >70%. Results A total of 87 plaques were evaluated. Mean age was 72 years (SD=7.7) and 79% were male. Pre-test probability were low, medium and high in 15.8, 26.3% and 57.9% of patients respectively. Mean calcium score was 1662, with an average dose of 7.5 mSv (67.9% retrospective studies). Nitrates were administered in 89.5% of patients, and 47.4% received intravenous beta-blockers. Sensitivity, specificity, positive predictive value, and negative predictive value to detect lesions > 50% improved from 94%, 57%, 38%, 97% with conventional images to 94%, 82%, 59%, 98% with 100 keV virtual monoenergetic images. Conclusion Spectral reconstructions significantly enhance diagnostic accuracy in coronary CT angiography of severely calcified coronary arteries.

VERMONT non-optimised: can baseline diagnostic catheter images be used to measure angiography based CAAS-vFFR?

Abstract Background We have previously reported strong diagnostic accuracy and validity of angiography-based vessel Fractional Flow Reserve (CAAS-vFFR) compared to conventional wire based Fractional Flow Reserve (FFR)(1). The CAAS-vFFR system requires at least two additional optimised angiographic cine images taken after intracoronary glyceryl trinitrate administration, separated by ≥ 30 degrees at a frame-rate of ≥ 15 frames/seconds with minimal overlap and foreshortening, no table movement and adequate contrast opacification. At present, there is a paucity of data regarding the validity of using baseline non-optimised diagnostic cine images in the assessment of CAAS-vFFR. Purpose To assess the concordance and validity of using baseline non-optimised diagnostic cine images in measuring angiography based CAAS-vFFR. Methods We conducted an investigator-initiated, single centre, blinded, prospective observational study performing wire based FFR and CAAS-vFFR conducted simultaneously in patients undergoing routine wire-based FFR for intermediate coronary stenoses. All eligible patients had baseline diagnostic and optimised guide-catheter based angiographic images acquired. Results 195 consecutive patients with 205 lesions were recruited over 19 months; 56 (27.3%) lesions were excluded due to inadequate baseline cine angiogram images (Picture 1). 102 (68.5%) had stable symptoms and 107 (71.8%) were male. The median age was 65.0 years (interquartile range 59.0 – 73.0) and mean body-mass-index was 29.2 kg/m2 (± 5.8). There were 117 (78.5%) lesions in the left anterior descending artery/diagonal branches, 20 (13.4%) in the right coronary artery and 12 (8.1%) in the left circumflex artery/marginal branches. There were 93 (62.4%) diffuse (≥ 20 cm), 23 (15.4%) bifurcation and 15 (10.1%) ostial lesions. The mean optimised vFFR and non-optimised vFFR were 0.80 (± 0.1) and 0.79 (± 0.1) respectively with a Pearson correlation of 0.87 (p<0.001). Overall, 52 lesions (34.9%) and 73 lesions (49.0%) had a wire-based FFR and non-optimised vFFR value of ≤ 80 respectively. The mean wire-based FFR and non-optimised vFFR were 0.82 (± 0.1) and 0.79 (± 0.1) respectively. Receiver operating characteristic (ROC) curve analysis revealed excellent diagnostic accuracy of non-optimised vFFR in predicting a wire based FFR of ≤ 80 (AUC 0.91; 95% CI; 0.87-0.96) (Picture 2). Baseline non-optimised diagnostic vFFR images produced a sensitivity of 94.2%, specificity of 75.3%, positive-predictive-value (PPV) of 67.1% and negative-predictive-value (NPV) of 96.1% compared with wire-based FFR. Conclusions CAAS-vFFR derived values from baseline non-optimised diagnostic cine images were strongly concordant with those derived from optimised images and displayed a high sensitivity and NPV compared to wire-based FFR. This reflects the potential for CAAS-vFFR to have broader clinical applications and be utilised as a retrospective screening tool for intermediate lesions.Excluded baseline angiogram lesionsROC Curve

Gene-gene and gene-environment interaction in coronary artery disease risk

Abstract Coronary Artery Disease (CAD) is a lethal illness that kills millions of individuals each year worldwide. This disorder is multifactorial, resulting in the complex interplay of genetic, epigenetic, and environmental factors. Exploring gene-gene and gene-environment interactions is essential to understanding the aetiology of common complex diseases like CAD. Aim We proposed investigating the interaction between two genetic variants robustly associated with CAD by GWAS (MTHFR rs1801133 and APOE rs7412/rs429358) in cardiovascular susceptibility. After that, consider whether there was a new interaction between this genetic association and environment (hypertension, dyslipidemia and smoking). Methods A case-control study enrolled 3,157 individuals, 1,721 coronary patients (with at least 70% stenosis of one or more major coronary arteries or its primary branches on the coronary angiography) and 1,436 controls without CAD. Traditional risk factors were investigated, and the two polymorphisms were performed by TaqMan real-time PCR. Bivariate analysis was used to study genotypic proportions between CAD and non-CAD patients with respective odds ratios (OR). Logistic regression analysis displayed the interaction between the two genetic variants each other and with some important environmental risk factors. Results In bivariate analysis, the genetic models were studied for both genes, being the dominant model the one which showed significance for CAD. In MTHFR, 57.8% of the patients and 53.4% of the controls presented the CT+TT genotype (OR=1.20; p=0.013). In APOE, 26.5% of the patients and 22.3% of the controls had E2E4;E3E4+E4E4 (OR=1.26; p=0.006). The first multivariate logistic regression showed a synergistic interaction between the two genetic variants (OR=1.50; p=0.001). After adjusting for conventional risk factors, the logistic regression analysis entered the MTHFR rs1801133 and APOE rs7412/rs429358, showing a combined interaction effect between those genes and smoking status with an OR of 3.44 (p<0.0001), with hypertension (OR=1.55; p=0.002) and with dyslipidemia (OR=1.71; p<0.0001). Conclusion According to our results, the genetic interaction between APOE and MTHFR synergistically affected the susceptibility to CAD. This interaction, linked to conventional risk factors, consistently increased the risk of CAD in our population, particularly in the group of genetic carriers who did not quit smoking.

A new free radical scavenger, resorcimoline, prevents ischaemia/reperfusion injury in the heart

Abstract Introduction Ischaemic heart disease remains the leading cause of death worldwide. Early coronary revascularisation is the most important treatment. Recent findings have revealed that reactive oxygen species (ROS) can lead to tissue damage following coronary artery revascularisation, known as ischaemia-reperfusion injury. In this study, we focused on resorcimoline, a new free radical scavenger that was generated during the synthesis of dimethylresveratrol and dimethylpiceatannol. Last year, we reported the scavenging activity in vitro against multiple ROS, confirmed by the electron spin resonance spectrometry (Ref. 1). Purpose This study aimed to assess the potential of resorcimoline as a novel therapeutic treatment for reducing the degree of infarction caused by myocardial ischaemia, by eliminating ROS generated during myocardial ischaemia-reperfusion. Methods Nine-to-eleven-week-old male Wistar rats were subjected to acute myocardial ischaemia induced by ligation of the left anterior descending coronary artery for 30 minutes, followed by reperfusion for 24 hours. Rats received intravenous injections of resorcimoline at 6 mg/kg before coronary ligation or saline as a control (n = 9 vs. n = 8). The heart sections were double-stained with Evans blue 1% and triphenyltetrazolium chloride 1% to assess infarct area and area-at-risk. For immunohistochemical study, the other ischaemia/reperfusion models were treated with resorcimoline and saline (n = 7 vs. n = 7) as above, and the middle parts of the hearts were embedded in optimal cutting temperature compound and quickly frozen. In the H＆E-stained section, the infarct border zone was defined as a 2-mm band surrounding the necrosis area. Troponin I levels in serum were measured using ELISA. Primary cultured cardiomyocytes were treated with 10 μM angiotensin II for 3.5 hours and then exposed to resorcimoline for 30 minutes at an increasing dosage. A cellular ROS assay kit was used to assess the levels of ROS in the cardiomyocytes and the number of cells was counted with DAPI stain using an image processing software. Results Infarct size in resorcimoline-treated animals was significantly smaller than in control animals (41.8±19.4% vs. 60.8±12.9%, p=0.03, Fig. 1A) and area-at-risk was not significantly different (58.0±27.8% vs. 51.9±18.5%, p=0.61). Apoptotic cells in the border zone were significantly reduced in resorcimoline-treated animals (32.0±11.7% vs. 55.1±16.9%, p=0.01, Fig. 1B). Troponin I levels in resorcimoline-treated animals were significantly lower than in control animals (4524±3596 vs. 7856±4653, p=0.04, Fig. 1C). resorcimoline significantly reduced angiotensin II-induced ROS in cardiomyocytes in a concentration-dependent manner (Fig. 2A,B). Conclusion This novel compound, resorcimoline, can reduce infarct size induced by coronary ischaemia-reperfusion injury by reducing the ROS damage to myocardiocytes in the border zone and cellular ROS levels in cardiomyocytes.

Fully automated detection of anomalous aortic origin of the coronary arteries in coronary CT images: a novel artificial intelligence-based screening tool

Abstract Background Anomalous Aortic Origin of the Coronary Artery (AAOCA) is a rare congenital disease that can be easily overlooked during contrast-enhanced Coronary Computed Tomography Angiography (CCTA) image analysis. Objective In this study, we aimed to develop a novel artificial intelligence-based screening tool to automate the detection of AAOCA in CCTA images. Method We enrolled 127 patients from the coronary artery anomaly registry from two centers with AAOCA diagnosis based on CCTA as well as 413 normal cases. A deep learning model was developed to automatically segment the aorta and the left ventricle (LV), after which the images were automatically cropped to the aortic root and LV intersection with a box size of 6 cm3. The images were then clipped to Hounsfield Units ranging from -400 to 750 and normalized to -1 to1. These cropped regions were fed into different residual convolutional neural networks (ResNet, with different depths 10, 18, 34 and 50) to detect AAOCA. Model development (parameter and hyperparameters optimization) was performed on the training and validation sets (70/10%), and finally, it was tested on the 20% untouched test set. Various classification metrics were reported for the detection of AAOCA. Results ResNet-10 achieved an AUC of 0.91 (sensitivity: 0.89, specificity: 0.86), while ResNet-18 showed improved performance with an AUC of 0.95 (sensitivity: 0.89, specificity: 0.95). ResNet-34 achieved an AUC of 0.94 (sensitivity: 0.83, specificity: 0.96), and ResNet-50 excelled with the highest AUC of 0.96 (sensitivity: 0.89, specificity: 0.95), indicating its superior capability in accurately identifying AAOCA. Conclusion We developed a high-performance AI tool for the fully automated detection of AAOCA using CCTA images. This tool can be used to evaluate large patient cohorts and detect AAOCA in extensive databases. Moreover, it can operate seamlessly alongside clinical assessments of CCTA scans, providing real-time alerts to medical personnel about potential AAOCA findings. This enhances diagnostic efficiency and supports early intervention in cardiovascular care.

Low ambient temperature and incident myocardial infarction with or without obstructive coronary arteries: a Chinese nationwide study.

Although non-optimum ambient temperature is a major non-traditional risk factor for acute myocardial infarction, there is no prior knowledge on whether non-optimum ambient temperature could differentially affect myocardial infarction with obstructive coronary artery disease (MI-CAD) and myocardial infarction with non-obstructive coronary arteries (MINOCA). Using the Chinese Cardiovascular Association database-Chest Pain Center Registry, a nationwide, time-stratified, case-crossover investigation was conducted from 2015 to 2021. Meteorological data were obtained from an established satellite-based model, and daily exposures were assigned according to the onset of myocardial infarction in each patient. A conditional logistic regression model combined with distributed lag non-linear models (10 days) was used to estimate the exposure-response relationships. A total of 83 784 MINOCA patients and 918 730 MI-CAD patients were included. The risk of MINOCA and MI-CAD associated with low temperature occurred at lag 2 day and lasted to 1 week. Extremely low temperature was associated with a substantially greater odds ratio (OR) of MINOCA [OR 1.58, 95% confidence interval (CI) 1.31-1.90] than MI-CAD (unmatched: OR 1.32, 95% CI 1.23-1.43; equally matched by age and sex: OR 1.25, 95% CI 1.04-1.50), compared with the corresponding reference temperatures (30°C, 35°C, and 30°C). Stronger associations were observed for patients who were aged ≥65 years, female, or resided in the south. There was no significant difference for the impacts of high temperature on MINOCA and MI-CAD. This nationwide study highlights the particular susceptibility of MINOCA patients to ambient low temperature compared with that of MI-CAD patients.

Myocardial Bridging: a bridge to spasm?

Abstract Introduction Myocardial bridges (MBs) represent a congenital anomaly where a segment of a coronary artery passes through the myocardium, resulting in systolic compression. The role of MBs in causing chest pain has been debated, as coronary blood flow occurs primarily in diastole. MBs are generally considered benign, there is growing evidence implicating them in the pathogenesis of coronary artery spasm (CAS). However, the prevalence of CAS in patients in Europe with MBs, particularly assessed through acetylcholine (ACh) testing, remains poorly defined. Methods We conducted a retrospective analysis of consecutive patients with angina with no obstructive CAD (ANOCA), ischemia with no obstructive CAD (INOCA), or myocardial infarction with no obstructive coronary arteries (MINOCA) undergoing ACh testing between 2021 and 2024 at our centre. Patients with documented MBs on coronary angiography were included. The presence of epicardial CAS, defined as >90% reduction in coronary diameter with symptoms and/or ischemic electrocardiographic changes, was assessed during ACh provocation testing. Clinical characteristics, Fractional flow reserve (FFR), resting full-cycle ratio (RFR), coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were also analyzed. Results From a total of 299 patients who underwent ACh Testing, 21 patients were identified with MBs, (17 Male, 4 Female). The prevalence of focal CAS in the MB among these patients was 90%. None of these patients had abnormal hyperemic (FFR) or non-hyperemic (RFR) measurements. 9 of the 21 patients with MB had increased IMR, and only 1 had a CFR < 2. 1 Patient had both microvascular CAS in addition to focal epicardial CAS. Conclusion This analysis provides valuable insights into the prevalence of CAS in patients with MBs undergoing ACh testing. The findings underscore the importance of considering CAS in the evaluation and management of patients with MBs, particularly during provocative testing. Further prospective studies are warranted to validate these findings and elucidate the clinical implications for risk stratification and treatment strategies in this patient population.

Predictors of debulking devices use by coronary artery calcification classification using cardiac CT

Abstract Background Multi-slice computed tomography (CT) is useful for the non-invasive detection and quantification of coronary calcium burden. However, a definitive parameter based on CT imaging for predicting the need for debulking devices, such as rotational atherectomy (RA) and orbital atherectomy (OAS), has yet to be established. Purpose We aimed to develop a calcification risk score using cardiac CT to predict the use of debulking devices during coronary intervention. Methods In this retrospective, multi-center, observational study in Japan, patients who underwent percutaneous coronary intervention (PCI) were screened. Inclusion criteria were (1) cardiac CT within 6 months prior to PCI, (2) moderate or severe coronary calcification detected on CT, and (3) de novo lesions in a native coronary artery. A total of 349 lesions in 343 patients from 13 hospitals, there were 124 lesions that were treated with debulking devices and 225 lesions without debulking devices. Cardiac CT images were analyzed for circumferential degree, longitudinal length, intracoronary distribution of calcification, peak density, mean density, vessel bend and presence of bifurcation lesions. Data from a random two-thirds (the derivation cohort, n=247) were used to develop a new risk prediction model, which was then tested in the remaining one-third (the validation cohort, n=102). Odds ratios and the risk prediction model were developed using a logistic regression model. The predicted risk was translated into a simplified scoring system (Figure 1A). Results RA was used in 111 lesions and OAS in 23 lesions. Factors selected in the model included circumferential degree (≥270°: 3 points), bifurcation (2 points), longitudinal length (≥8mm: 1 point), and mean density (≥600 HU: 1 point) (Figure 1B). This model demonstrated good discrimination (c-statistic=0.772) and calibration (Hosmer–Lemeshow χ²-statistic=0.885; P=0.64) in the validation cohort (Figure 2). Conclusions The new prediction model based on cardiac CT performed well in predicting the need for debulking devices. This could serve as an objective tool to support a clinical decision to use debulking devices even in cases where intravascular imaging is not applicable.Study flow and Cardiac CT calcium scoreDiscrimination and Calibration

Prevalence of coronary microvascular disease in myocardial infarction with non-obstructive coronary artery disease

Abstract Background Six percent of patients presenting with acute myocardial infarction (MI) have MI with non-obstructed coronary artery disease (MINOCA). Coronary microvascular disease (CMD) is common in angina with non-obstructive coronary artery disease (ANOCA), but its prevalence and severity in MINOCA is undefined. Purpose Patients with CMD may have elevated risk of myocardial infarction despite no significant stenosis. We tested the hypothesis that patients with MINOCA have more significant burden of CMD than patients with ANOCA. Methods A retrospective case-control study was performed on patients who underwent invasive testing for signs of coronary ischemia and found to have non-obstructive disease (stenoses< 50%). Cases of MI were classified as MINOCA (n=87) and compared to patients with ANOCA (n=552). Patients with spontaneous coronary artery dissection, myocarditis, Takotsubo cardiomyopathy or prior atherothrombotic MI were excluded. Coronary catheterization was performed followed by invasive provocation testing with adenosine and acetylcholine using a Doppler flow wire. CMD was subdivided into endothelium-independent, defined as coronary flow reserve (CFR) < 2.5 with intra-coronary adenosine, and endothelium dependent, defined as < 50% increase in coronary blood flow with acetylcholine. Epicardial vasoconstriction > 90% with typical anginal symptoms was classified as epicardial vasospasm. Results There was no difference in age, sex or traditional coronary risk factors between the MINOCA and ANOCA groups (Table 1). Fifty (57%) of patients with MINOCA had type 2 MI secondary to supply-demand mismatch. Both MINOCA and suspected ANOCA patients had a high prevalence of CMD (71% vs 67%) and endothelium-independent CMD is more prevalent in MINOCA (64.5% vs 50.4%). Although odds of endothelium-dependent CMD were similar, the CFR within this group and CMD overall was worse in MINOCA patients (Figure 1). There was no difference in epicardial spasm. Conclusion Coronary microvascular disease and vasomotor dysfunction are common in patients with MINOCA, with a higher prevalence of endothelium-independent CMD and more severe CMD overall compared to patients with ANOCA. Treatment of CMD in patients with MINOCA may help reduce recurrence and warrants further investigation.

Drug eluting stents trigger the secretion of inflammatory proteins in an experimental in vitro study

Abstract Introduction Ischemic cardiovascular diseases commonly appear following the occlusion of one or more of the coronary arteries. Drug eluting stents (DES) constitute the gold standard to help to keep open the arteries and maintain the blood flow. After their placement into the coronary arteries, they stay in direct contact with the blood stream, disturbing the physiological conditions and interacting with several cells and proteins within the surrounding blood and vessel wall. Besides the beneficial effects of DES, their clinical application is also associated with complications, such as (late) stent thromboses. Previous studies have shown that thrombosis and inflammation are tightly linked with each other by activating inflammatory cells and secreting cytokines and chemokines to further promote an inflammatory surrounding. However, the influence of DES and their components on the inflammatory cascade and their corresponding players was not investigated yet. Methods To investigate the inflammatory secretome in response to DES, we performed an in vitro study with isolated human peripheral blood mononuclear cells (PBMCs). Therefore, PBMCs were isolated from the whole blood of four healthy volunteers. In total, 63 stents were used in the study, including Medtronic Resolute Onyx (n=37), Abbott XIENCE Sierra (n=5), Boston Scientific SYNERGY (n=4), Terumo Ultimaster (n=3), and Biotronik Orsiro (n=14). We measured the secretion of cytokines and chemokines, including IL-1β, IL-6, TNF-α, IL-8, and IL-12, as well as ICAM-1, VCAM-1, and MCP-1 by commercially available enzyme-linked immunosorbent assay (ELISA). Results Our results showed that DES significantly increase the secretion of the cytokines IL-1β (p=0.0005), and IL-6 (p=0.0002), as well as the chemokine IL-8 (p=0.0010). Additionally, we also detected an elevation of the reaction product ICAM-1 (p=0.0003). Further analyses resulted in a reduced secretion of IL-1β, IL-6, TNF-α, IL-8, and ICAM-1 into the cells’ supernatants in response to Resolute Onyx stents, in comparison to the other stents. Moreover, multiple regression analysis revealed a high dependency of the inflammatory reaction on the elution drug, the polymer type and the stent’s length. Additionally, the material of the stent platform, as well as the polymer thickness further have impact on the cytokine and chemokine response of PBMCs. Conclusion Our study indicate that DES by themselves trigger an inflammatory reaction of blood cells by the secretion of cytokines and chemokines. Furthermore, we provided first insights into the composition of the inflammosome in response to DES. A triggered inflammation may increase the vulnerability for complications and the failure of the DES. As these complications were already observed in clinical studies, our results would potentially provide predictions about the application of certain DES designs and may help to choose the appropriate stents in the clinical setting.

The predictive value of coronary artery calcium deposit for cardiovascular events in patients treated with immune checkpoint inhibitor therapy

Abstract Background Immune checkpoint inhibitors (ICIs) are now a standard of care for the treatment of wide variety of cancers, due to their dramatically improved patient's outcomes. Nevertheless, their use may lead to significant cardiovascular immune-related adverse events (CV irAEs). Objectives We aimed to assess whether pre-treatment coronary artery calcium (CAC) deposit may play as a risk factor for CV irAEs development in patients treated with ICIs therapy. Methods A retrospective single center cohort of patients treated with ICIs therapy, who performed pre-treatment chest computed tomography. Visual CAC assessment was performed, categorized to positive or negative calcium deposit in the coronary arteries. Patients with pre-existing ischemic heart disease were excluded. The primary endpoint was to evaluate the association between positive CAC deposit and the composite CV irAEs, including myocarditis, acute coronary syndrome, heart failure, and arrhythmias. The secondary endpoint was to evaluate its association to all-cause mortality. Results The cohort included 238 patients, with mean age 65±13 years and 53% male representative. The most prevalent type of cancer was lung (36%) and the prominent ICIs regimen was pembrolizumab (54%). High incidence of cardiac risk factors was observed, including hypertension (39%), hyperlipidemia (35%) and diabetes (23%). Overall, 145 (61%) patients were included in the positive CAC deposit group. No significant differences were observed between the positive and negative groups regarding cancer type, ICIs therapy and baseline cardiac risk factors or medical therapy. Over a 12-months follow-up period, positive CAC deposit was not associated with the development of CV irAEs (p=0.139), or increased all-cause mortality (p=0.884). Conclusion The presence of pre-treatment positive CAC deposit did not demonstrate a predictive role in assessing the risk of CV irAEs or all-cause mortality in patients treated with ICIs.

Coexistence of coronary microvascular dysfunction and left ventricular hypertrophy can predict prognosis of patients with nonobstructive coronary arteries

Abstract Background Previous studies have reported that coronary microvascular dysfunction (CMD) and left ventricular hypertrophy (LVH) were associated with adverse cardiovascular events. The aim of this study was to determine the prognostic impact of coexistence of abnormal coronary flow reserve (CFR) and left ventricular mass index (LVMI). Methods and results This study included 297 patients who underwent intracoronary physiological assessment including CFR for suspected myocardial ischemia without significant stenosis in the epicardial coronary artery at our hospital from December 2019 to March 2023. Of 297 patients (female: n=89 [30%], age: 70±11 years), 93 (31%) had CMD (CFR<2.5) and 133 (45%) had LVH (LVMI>95 g/m2 for female and >115 g/m2 for male). We excluded patients with history of heart failure (HF). Patients were classified into 4 groups based on the cut-off values of CFR and LVMI: group 1 (no CMD nor LVH, n=109); group 2 (only LVH, n=95); group 3 (only CMD, n=55) and group 4 (both CMD and LVH, n=38). Patients of group 4 had a larger proportion of female (female 19%, 34%, 24% and 61% in group 1 to 4 respectively). There was no significant difference in left ventricular ejection fraction between patients of each groups. Clinical follow-up was performed for major adverse cardiovascular events (MACE) including cardiovascular death, myocardial infarction and hospitalization for new-onset HF. During a median follow-up of 753 days, the cumulative MACE-free survival rate at 2 year were 99.0%, 98.9%, 95.6% and 90.0% in groups 1 to 4. Group 4 showed significantly higher risk of MACE at 2 year compared with group 1 (hazard ratio [HR] 2.6; 95% confidence interval [CI] 1.3-5.3; p=0.009). Notably, Group 4 showed the highest incidence of hospitalization for new-onset HF than any other groups. Conclusion Patients with both CMD and LVH showed significantly higher risk for MACE and new onset of HF. The combined classification based on CFR and LVMI would identify the high-risk patients for MACE as well as new-onset HF.

Antiplatelet agents in patients with intermediate coronary artery stenosis and deferred revascularization

Abstract Background There is no specific recommendation regarding optimal antiplatelet therapy after deferral of revascularization in patients with established coronary artery disease. Objectives The current study investigated safety and efficacy of antiplatelet therapy in patients with intermediate coronary artery stenosis in whom revascularization was deferred based on fractional flow reserve (FFR). Methods In the Korean National Health Insurance Service database 2013-2020, we identified 4,657 patients who had intermediate coronary artery disease on angiography for which revascularization was deferred based on FFR. During this period, reimbursement criteria of FFR were patients with no previous evidence of myocardial ischemia and intermediate coronary artery stenosis (50-70%) by quantitative coronary angiography. Patients were then classified into two groups according to initiation of antiplatelet therapy after the index procedure. Primary efficacy outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, unplanned revascularization, and stroke, during 5 years of follow-up. Primary safety outcome was any gastrointestinal bleeding. Results After propensity score matching in a 1:1 ratio, there were 1,634 patients in antiplatelet therapy group and 1,634 in no therapy group (total N=3,268). The risk of MACCE was similar between the two groups (24.8% vs. 24.7%; adjusted hazard ratio [aHR], 0.97; 95% confidence interval [CI], 0.84-1.13; P=0.745). However, the risk of any gastrointestinal bleeding was higher in antiplatelet therapy group than no therapy group (2.2% vs. 1.2%; aHR, 2.07, 95% CI, 1.08-4.00). These results were consistently found in subgroup analyses. Conclusions In patients with intermediate coronary artery stenosis with deferred revascularization based on FFR, antiplatelet therapy was not associated with reduced risk of ischemic events but increased risk of gastrointestinal bleeding.

Increased circulating levels of standardized inflammatory and endothelial dysfunction biomarkers in patients with myocardial infarction with nonobstructive coronary arteries

Abstract Introduction Around 10% of patients with acute myocardial infarction (AMI) present with nonobstructive coronary arteries (MINOCA), for which the underlying pathophysiology is often uncertain. Our aim was to evaluate inflammatory burden and endothelial dysfunction in MINOCA patients by assessing biomarkers in both acute and stable phases. Methods An analytical and observational study at a University Hospital involving 166 MI patients admitted over the past 3years. Following ESC guidelines, patients were categorized into MINOCA or myocardial infarction with significant coronary artery disease (MI-CAD) groups. Circulating levels of inflammatory biomarkers (interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) and high-sensitivity C-reactive protein(hs-CRP)) and of endothelial dysfunction (asymmetric dimethylarginine (ADMA)) were measured in 44 MINOCA patients and 122 MI-CAD patients at acute phase (admission and discharge) and stable phase (2months after MI). As biomarker levels may vary with MI size, each value was standardized by dividing it by the peak troponin, resulting in a biomarker/troponinT ratio. We evaluated the effects of standardized (SB) and non-standardized (NSB) biomarker values using a multivariate regression model adjusted for age and sex. Results We analyzed 166 patients (median age:68 years, 70% males). MI-CAD patients had higher peak high-sensitive troponinT (hs-TnT) levels upon admission compared to those with MINOCA (1491ng/L vs 247ng/L,p<0.001),likely due to larger infarctions generating higher levels of inflammation. When examining the association between infarct size, as measured by peak hs-TnT values, and biomarker levels, we observed a significant dose-response relationship for hs-CRP at admission (βcoefficient 0.16 [95%CI,0.02-0.29],p0.02) and IL-6 at admission (βcoefficient 0.15 [95%CI,0.04-0.27],p0.01). Significant positive associations were found between MINOCA and all SBs, both during the acute phase and in follow-up. During the acute phase ORs ranged from 1.35to2.7 (p<0.05) for inflammatory biomarkers and from 2.34 to 2.76 (p<0.01) for ADMA. In the stable phase ORs ranged from 1.49to3.06 (p<0.05) for inflammatory biomarkers, and OR was 2.79(p<0.01) for ADMA (Figure 1). In contrast, none of the NSBs were associated with MINOCA. Regarding temporal biomarker changes, during the acute phase of MI and 2 months post-event, both MINOCA and MI-CAD patients showed similar trends. However, MINOCA patients consistently maintained elevated inflammatory activity and ADMA concentrations only when biomarkers were standardized by infarct size (Figure 2). Conclusions Higher levels of SBs were consistently associated with MINOCA, both during the acute phase of the event and in follow-up, compared to MI-CAD. Consequently, this study suggests that the inflammatory burden, measured by heightened levels of standardized inflammatory biomarkers, and endothelial dysfunction, as measured by ADMA, may play a role in the pathophysiology of MINOCA.Boxplots for SBs at three time points.Temporal changes in biomarker levels.

Screening for subclinical atherosclerosis in patients clinically diagnosed with familial hypercholesterolemia and determination of imaging-guided patient management strategy

Abstract Introduction Familial hypercholesterolemia (FH) is a monogenic dyslipidemia characterized by elevated plasma LDL-C levels, leading to early cardiovascular disease. The Dutch Lipid Clinic Network (DLCN) score is the most widely used clinical scoring system in current practice. Subclinical atherosclerosis is defined as the detection of atheromatous plaques in arterial territories, such as coronary, carotid or iliofemoral, before a symptom or event occurs. It is an early indicator of atherosclerotic burden. In this study, we investigated the presence of subclinical atherosclerosis in FH patients with a definite or probable clinical diagnosis according to DLCN score. We also tried to identify independent predictors of subclinical atherosclerosis. Methods This study is a single-center, prospective, and cross-sectional investigation involving a cohort of 215 FH patients. These patients are primary prevention patients and among them, 120 patients received a definite clinical diagnosis, while 95 patients received a probable clinical diagnosis based on the DLCN score. Carotid USG and Femoral USG were performed to screen for subclinical atherosclerosis and CAC score was calculated by non-contrast CT. Apo A-I, Apo B and Lp (a) measurements were analyzed by immunonephelometric method. Results The study population consisted of 136 (63%) women and 79 (37%) men. The mean age was 54 years (43-62) and the stigmata rate was 18%. Initially, 17% of patients were on aspirin, and 32% were receiving statin treatment; however, following subclinical atherosclerosis screening, these proportions significantly increased (aspirin usage to %32 and statin usage to %96) within the population. 148 patients (69%) had subclinical atherosclerosis in at least one site. Upon regional analysis, subclinical atherosclerosis rates were 48% in the coronary arteries, 47.5% in the carotid bifurcation region, and 40.5% in the femoral bifurcation region. Additionally, 25% of patients had atherosclerosis at one site, 27% at two sites, and 17% at all three sites. Age, male gender, pretreatment LDL-C level, Apo A-I/Apo B ratio and DM were identified as independent predictors of the presence of subclinical atherosclerosis in the FH patients. Furthermore age, male gender, pretreatment nonHDL-C level, Lp (a) ≥ 30 mg/dl and presence of femoral plaque were identified as independent predictors of coronary atherosclerosis. Conclusion Subclinical atherosclerosis is prevalent among FH patients, and this study has identified independent predictors associated with presence of subclinical atherosclerosis. However, despite this heightened risk, medication utilization among these patients remains below optimal levels and only a small proportion of the population has achieved their treatment goals. Our study highlights the influence of subclinical atherosclerosis on treatment approaches, as demonstrated by the notable rise in statin and aspirin utilization observed after screening.Clinical and biochemical characteristicsSubclinical Atherosclerosis Rates

Mortality related to left ventricular ejection fraction and obstructive coronary artery disease in non-ST-segment elevation myocardial infarction

Abstract Background Extent of coronary artery disease (CAD) and the severity of reduced left ventricular ejection fraction (LVEF) have both been associated with the prognosis after non-ST-segment elevation myocardial infarction (NSTEMI). However, the contemporary mortality associated with the extent of obstructive CAD over a range of LVEF remains uncertain. Purpose The aim of this study was to assess the impact of CAD and LVEF on all-cause death following a first-time NSTEMI. Methods We included consecutive first-time NSTEMI patients undergoing coronary angiography from 2010 to 2021 in Western Denmark. Patients were stratified by extent of obstructive vessel disease (VD; 1, 2, or 3VD) and LVEF (≥51%, 41-50%, or 10-40%). Patients with previous myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting were excluded. The primary outcome was all-cause death. We calculated 5-year cumulative incidence proportions (CIP) as a measure of absolute risk and adjusted hazard ratios (HR). Results A total of 8,770 patients with first-time NSTEMI and obstructive CAD were examined with coronary angiography. Two-thirds were male and median age was 68 years (Q1-Q3: 58-78). The increase in mortality associated with decreasing LVEF was greater than observed by extent of CAD (Table). Thus, the 5-year mortality increased stepwise by extent of CAD from 14% for 1VD to 31% for 3VD (adjusted HR 1.35, 95% CI:1.19-1.54), but from 12% for LVEF ≥51% to 40% for LVEF 10-40% (adjusted HR 2.32, 95% CI: 2.04-2.65). When combining LVEF and extent of CAD, an increase in 5-year mortality was found from 9% for 1VD and LVEF ≥51% to 46% for 3VD and LVEF 10-40% (risk difference of 37.1%; Figure). Correspondingly, using 1VD and LVEF ≥51% as reference, the adjusted HRs increased gradually with extent of CAD and decline in LVEF to 3.05 (95% CI: 2.51-3.70) for patients with 3VD and LVEF 10-40% (Table). Conclusion In a contemporary all-comers cohort of first-time NSTEMI patients, increasing extent of CAD and declining LVEF are both associated with a gradual increase in 5-year mortality. Our data suggest that the level of LVEF reduction was more strongly associated with 5-year mortality than CAD extent.

Clinical outcome based on functional complete revascularization in patients with three-vessel coronary artery disease: The FAME 3 Trial

Abstract Background Anatomic complete revascularization after angiography-guided percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. The impact of functional complete revascularization (PCI of all fractional flow reserve (FFR) positive lesions) in patients with 3-vessel coronary artery disease (3VD) amenable to PCI or coronary artery bypass grafting (CABG) is unknown. Purpose To investigate the clinical impact of functional complete revascularization after FFR-guided PCI in the FAME 3 trial Methods The FAME 3 trial is a multicenter, international, randomized study comparing FFR-guided PCI with CABG in patients with angiographic 3VD. This pre-specified sub-study evaluated the impact of functional complete revascularization after PCI on the primary endpoint of death, myocardial infarction (MI), or stroke at 3 years. The degree of functional complete revascularization was quantified by calculating the residual functional SYNTAX score (rFSS), defined as the residual anatomic SYNTAX score based on post-PCI angiography minus any FFR-negative deferred lesions. Results Of the 757 patients treated with FFR-guided PCI, the rFSS could be calculated by the core laboratory in 81% (n=601). Among the angiographically significant lesions, PCI was deferred based on FFR in 17% (51 % of patients had deferral of at least one lesion). The patients were divided into two groups according to acceptable functional complete revascularization: rFSS 0-8 (63%) and functional incomplete revascularization: rFSS>8 (37%). The cumulative incidence of death, MI, or stroke at 3 years was significantly lower in patients with rFSS 0-8 (9% vs. 17%, Hazard ratio[HR]:0.5, 95% confidence interval[CI]:0.3-0.8, p=0.006) compared with rFSS>8. In comparison with the CABG arm, the patients with rFSS 0-8 had similar outcome (HR:0.97, 95%CI:0.6-1.5, p=0.87), while in those with rFSS >8 outcome was worse (HR:1.9, 95%CI: 1.3-2.8, p=0.002) (Figure). There was no difference in death, MI or stroke in CABG patients with or without anatomic complete revascularization. In a multivariate-adjusted model, rFSS>8 showed a significant association with death, MI or stroke at three years (adjusted HR: 1.83, 95% CI: 1.09-3.09, p=0.02). Conclusions Acceptable functional complete revascularization with FFR-guided PCI in patients with 3VD is an independent predictor of death, MI or stroke at three years and can be achieved in 63% of patients resulting in similar outcomes compared with CABG.

Serial quantitative stress perfusion cardiac magnetic resonance in patients undergoing coronary artery bypass grafting; prediction of symptomatic benefit

Abstract Background Serial multiparametric cardiovascular magnetic resonance (CMR) in patients undergoing coronary artery bypass grafting (CABG) may provide mechanistic insight into dynamic and persistent abnormalities of the myocardium in patients with stable coronary artery disease (CAD). Objectives To assess for dynamic CMR markers of myocardial hypoperfusion and cardiac remodelling in patients undergoing CABG. Methods Patients with CAD awaiting elective CABG were recruited into an observational cohort study. Baseline evaluation included bloods, Seattle Angina Questionnaire-7, and adenosine stress perfusion CMR. Automated fully quantitative stress and rest myocardial blood flow was calculated, alongside assessment of the visual ischaemic burden. Native and post-contrast septal T1 indices were also measured. Repeat evaluation at 6-12 months post CABG was performed. Results Of 43 patients who underwent serial evaluation with CMR (mean age 62.1±9.3, median LVEF 68% [IQR: 62-73%]), there was improvement in the median visual ischaemic burden (18% [IQR: 11-21] vs 42% [IQR: 27-51], P<0.001), mean global stress myocardial blood flow (1.5±0.5 ml/min/g vs 1.3±0.5 ml/min/g, P=0.002) and median global myocardial perfusion reserve (2.4 [IQR: 1.7-2.8] vs 1.7 [IQR: 1.4-2.2], P=0.002) following CABG. Greater improvement in the SAQ-7 summary score was associated with a larger visual ischaemic burden at baseline (ρ=0.44, P=0.004) and a greater decrease in the visual ischaemic burden following CABG (ρ=-0.38, P=0.02). Quantitative MBF metrics did not associate with baseline or change in SAQ-7 summary score. Mean LV extracellular matrix volume decreased following CABG (16.6±3.6ml/m2 vs 18.2±4.6ml/m2, P=0.009). Conclusion Multiparametric CMR identifies dynamic changes in markers of myocardial perfusion and interstitial fibrosis in patients following CABG. Visual assessment of inducible myocardial hypoperfusion may identify patients who will derive the most symptomatic benefit from CABG. The results, however, suggest an important degree of residual inducible ischaemia and an unclear clinical role for CMR-derived MBF calculations.Serial CMR perfusion dataAssociation of SAQ with perfusion

Inclisiran-containing low-density lipoprotein cholesterol reduction effectively stabilizes atherosclerotic plaques

Abstract Background/Introduction Near-infrared spectroscopy (NIRS) allows to quantify lipid composition of coronary artery lesions. High plaque lipid content has been associated with increased adverse cardiovascular event risk. Purpose Aim of this study was to evaluate atherosclerotic plaque lipid content reduction in association with low-density lipoprotein (LDL-C) lowering on the background of intensive hypolipidaemic therapy. Methods NIRS investigation was performed in stable coronary artery disease patients having 20-50% stenosis in the proximal or middle third of a coronary artery. Segment of interest was repeatedly evaluated after 15 months. Lipid-rich plaques (LRPs) were defined as lesions with maximum lipid-core burden index within 4 mm (maxLCBI4 mm) >250. Study participants were taking high-intensity statin (atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg) with or without ezetimibe for a run-in period of 4-6 weeks. Afterwards, in patients not achieving LDL-C level <1.8 mmol/l, add-on inclisiran was started. Baseline LDL-C was defined as the level at the time of initiation of optimal lipid-lowering therapy. Statistical significance level of 0.05 was set. Results Data of 36 patients was analyzed. Mean baseline maxLCBI4 mm was 203.9, reduced by 39.8% (-81.1, 95%CI -129.2 to -33.0) at 15-month follow-up (P=0.003). In 15 patients LRPs were detected with mean baseline maxLCBI4 mm 363.5, which was decreased by 35.8% (-130.3, 95%CI -235.0 to -25.7) (P=0.020). Mean LDL-C level at baseline was 2.5 mmol/l among all participants, lowered by 32.0% (-0.8, 95%CI -1.1 to -0.5) after 15 months of treatment (P<0.001). 19 patients received inclisiran in addition to high-dose statin and optional ezetimibe therapy. In 24 patients achieving LDL-C target <1.8 mmol/l at 15-month follow-up, a significant maxLCBI4 mm reduction from 208.5 by 48.4% (-101.0, 95%CI -169.3 to -32.7) was established (P=0.010). Among those having LDL-C >1.8 mmol/l, maxLCBI4 mm reduction from 194.7 by 21.2% (-41.25, 95%CI -94.7 to 12.2) was observed, however the change was not statistically significant (P=0.114). Conclusion LDL-C lowering with high-intensity hypolipidaemic therapy, including escalation to proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition, demonstrated atherosclerotic plaque stabilization by NIRS-detected lipid content decrease.

Which is better for predicting and discriminating cardiovascular events: a traditional risk score, a calcium score or a genetic risk score?

Abstract Background The most effective approach to prevent coronary artery disease (CAD) in the general population remains to quantify the individual risk of CAD followed by controlling risk factors. There has been a lot of curiosity to investigate several scores individually for improving risk prediction. However, whether one would be better than the other in the same population is still unclear. Aim To evaluate the performance of the three individual scores, European SCORE2, Coronary artery calcium score (CACS) and a Genetic risk score (GRS), in predicting and discriminating cardiovascular (CV) events in an asymptomatic Portuguese population. Methods Prospective, observational population-based study, including 1002 asymptomatic subjects (mean age 53.1±6.8 years, 73.8% male) selected from a normal Portuguese population, without apparent CAD and diabetes at baseline. Data were recorded at the end of an extended follow-up (average 6.5±4.9 years). The European SCORE2, a computed tomography CACS, and a GRS were created to evaluate CV events’ predictive and discriminative ability through Receiver Operating Characteristics (ROC) analysis and Harrell’s C-statistics. Results ROC curve analysis showed 0.723 for SCORE2, 0.815 for CACS and 0.649 for GRS. Harrell’s C-statistics were 0.731 in the SCORE2, 0.785 for CACS and 0.684 for GRS. Conclusion The CAC score was the best individual score to predict and discriminate CV events in our asymptomatic population. Its capacity to identify high-risk individuals and those asymptomatic with subclinical atherosclerosis may improve CV risk management strategies to prevent future cardiovascular events. This result can be explained because CAC score, more than a risk marker, represents the existence of disease in the vessel wall.