Coronary Ischemic Events Research Articles

Endothelial cellular response to oxidative stress key to proteasome inhibitor cardiovascular toxicity profile

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Karolinska Institutet Background/Introduction Proteasome inhibitors (PI) have contributed to longer survival in multiple myeloma although PI related cardiovascular adverse events are common. Associated to carfilzomib hypertension, coronary ischemic events and heart failure (both with reduced and preserved left ventricular ejection fraction). Here we explore the effect of PIs on endothelial gene expression. Methods Human aortic endothelial cells (HAEC) were incubated for 24 h with carfilzomib or bortezomib at different concentrations. Gene expression determined using using bcl2fastq (v2.20.0), and read quality was assessed using FastQC (v0.11.8). For each group the 100 genes with highest ratio were used for analysis of gene ontology (GO), biological processes using ClusterProfiler. The carfilzomib / bortezomib >1.5 was determined in the relevant GO groups. Results PIs induce gene expression related to inflammatory response and oxidative stress, more pronounced for carfilzomib. 44 / 31 genes related to "cytokine-mediated signaling pathway" and "response to oxidative stress pathway. NR4A3 was 15.5 fold above control while its increase with bortezomib was modest. Discussion Both carfilzomib and bortezomib induce genes related in inflammation and oxidative stress. Carfilzomib induced more pronounced upregulations in several genes, that stimulates expression of increased cellular respiration. Our result show a differentiated effect on endothelial cell gene expression by carfilzomib and bortezomib -a possible explanation to the differences in cardiovascular toxicity profile. Figure 1. Selected GO, Biological function characteristics calculated on the top 100 fold-change genes in each group. C2 high dose carfilzomib, B1 and B2 low and high dose bortezomib. C1 did not converge to any GO characteristics.

Independent Relationship of Lipoprotein(a) and Carotid Atherosclerosis With Long-Term Risk of Cardiovascular Disease.

Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person-years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long-term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19-2.21) than those with Lp(a) <10 mg/dL, and they exhibited a 10-year ASCVD incidence of 11.7%. This association exists even after adjusting for prevalent plaque. Moreover, participants with Lp(a) ≥30 mg/dL and prevalent plaque had a significant 4.18 times higher ASCVD risk than those with Lp(a) <30 mg/dL and no plaque. Higher Lp(a) concentrations are independently associated with long-term ASCVD risk and may exaggerate cardiovascular risk when concomitant with atherosclerotic plaque.

Current Management of In-Stent Restenosis.

In-stent restenosis (ISR) remains the primary cause of target lesion failure following percutaneous coronary intervention (PCI), resulting in 10-year incidences of target lesion revascularization at a rate of approximately 20%. The treatment of ISR is challenging due to its inherent propensity for recurrence and varying susceptibility to available strategies, influenced by a complex interplay between clinical and lesion-specific conditions. Given the multiple mechanisms contributing to the development of ISR, proper identification of the underlying substrate, especially by using intravascular imaging, becomes pivotal as it can indicate distinct therapeutic requirements. Among standalone treatments, drug-coated balloon (DCB) angioplasty and drug-eluting stent (DES) implantation have been the most effective. The main advantage of a DCB-based approach is the avoidance of an additional metallic layer, which may otherwise enhance neointimal hyperplasia, provide the substratum for developing neoatherosclerosis, and expose the patient to a persistently higher risk of coronary ischemic events. On the other hand, target vessel scaffolding by DES implantation confers relevant mechanical advantages over DCB angioplasty, generally resulting in larger luminal gain, while drug elution from the stent surface ensures the inhibition of neointimal hyperplasia. Nevertheless, repeat stenting with DES also implies an additional permanent metallic layer that may reiterate and promote the mechanisms leading to ISR. Against this background, the selection of either DCB or DES on a patient- and lesion-specific basis as well as the implementation of adjuvant treatments, including cutting/scoring balloons, intravascular lithotripsy, and rotational atherectomy, hold the potential to improve the effectiveness of ISR treatment over time. In this review, we comprehensively assessed the available evidence from randomized trials to define contemporary interventional treatment of ISR and provide insights for future directions.

Surgical outcomes of the systemic-to-pulmonary artery shunt: risk factors of post-operative acute events and effectiveness of regulation of pulmonary blood flow with metal clips.

The aim of this study was to analyze the risk factors for acute events after systemic-to-pulmonary shunt (SPS) and to investigate the effectiveness of pulmonary blood flow regulation with a metal clip. The case histories of 116 patients (78 biventricular [BV] and 38 single ventricle [SV] physiology) who underwent SPS between 2010 and 2021 were retrospectively reviewed. Our strategy was to delay SPS until 1month of age; pulmonary blood flow (PBF) regulation by partial clipping of the graft, if needed. Cases of aortic cross-clamping were excluded from this study. CPB was used in 49 (42%) patients: the median age at SPS was 1month (2days to 16years), and the sternotomy approach in 65. Discharge survival was 98.3% (114/116); hospital death occurred in 1.7% due to coronary ischemia. Inter-stage mortality occurred in 1.7% (shunt thrombosis, 1; pneumonia, 1). Pre-discharge acute events occurred in 7 patients (6.0%): thrombosis 3, pulmonary over-circulation 2, and coronary ischemia 2. Multiple logistic regression analysis revealed that pulmonary atresia with intact ventricular septum (PA/IVS) (p = 0.0253) was an independent risk factor for acute events. Partial clipping of the graft was performed in 24 patients (pulmonary atresia 15) and clip removal was performed by catheter intervention in 9 patients; no coronary ischemic events and graft injury occurred in these patients. Surgical outcomes after SPS were acceptable and metal clip regulation of pulmonary blood flow appears to be safe and effective. PA/IVS was still a significant risk factor for acute events.

Duration of DAPT After Stent Implantation, How Low Can We Go?

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the main actor in secondary prevention of recurrent coronary ischemic events and stent thrombosis. For this exact purpose the combination of two antiplatelet molecules have proven efficacy and superiority compared to monotherapy, aspirin alone, but this comes with an increased risk of major and potentially fatal bleedings, making the choice of the molecules and especially the duration of treatment a true challenge for every cardiologist. We are going to discuss some of the main factors that play a role in the decision, and the most important trials that studied the subject.

Syphilitic ostial coronary artery occlusion treated with percutaneous coronary intervention: Case series and literature review

IntroductionNon-atherosclerotic causes of acute coronary syndrome (ACS) are important contributors to a substantial number of acute ischemic coronary events. Syphilitic aortitis is a rare complication of tertiary cardiovascular syphilis that may result in ostial coronary artery stenosis, aortic insufficiency, and ascending aortic aneurysm. MethodsIn this manuscript, we present two Case Reports of patients with bilateral syphilitic coronary artery ostial occlusion, and we review the associated literature. The immunofluorescent test was positive for syphilis in both patients. ResultsDiagnostic coronary angiography revealed bilateral occlusions of the left main coronary artery (LMCA) and right coronary artery (RCA), which were successfully treated with percutaneous coronary intervention (PCI) with bare metal stents (BMS). After deployment of the stents, arterial blood flow was re-established with TIMI flow grade 3. DiscussionThe angiographic finding of bilateral coronary ostial lesions in young patients should raise the suspicion of cardiovascular syphilis. Options for revascularization should be discussed amongst the patient and the Heart Team. PCI may be an option for treatment of isolated syphilitic coronary stenosis in the setting of acute hemodynamic instability or chronic inflammation.

Variation in Left Anterior Descending Coronary Artery Accumulated Dose Estimates during Breast Cancer Radiotherapy

Left anterior descending (LAD) coronary artery RT dose has been associated with the risk of coronary ischemic events in patients with breast cancer treated with radiotherapy (RT). However, consensus dose constraints commonly utilize mean heart dose, which has been shown to be an inadequate surrogate for LAD dose. Given the LAD is adjacent to the steep dose gradients of the left breast/chest wall, we hypothesize that variations in patient positioning or depth of breath hold may contribute to significant deviations in daily LAD dose exposure compared to predicted. Our objective was to investigate variations in accumulated LAD dose in patients with left-sided breast cancer treated with RT. Retrospective analysis of 10 consecutive patients with left-sided breast cancer treated between 2019-2022 with volumetric modulated arc therapy (VMAT) in the supine position. RT was delivered using daily cone beam computed tomography (CBCT) image guidance with deep-inspiratory breath hold technique and an optical surface monitoring system. Daily CBCT scans were individually registered to each planning CT based on daily positional changes. The LAD was manually segmented and transformed to each CBCT. Daily fractional dose was calculated (mean, volume receiving 15 Gy [V15 Gy], V30 Gy, and max) and summed to produce an accumulated dose which was compared to the predicted dose. Significant deviations in accumulated dose were defined as at least ±15% from predicted. The RT targets included breast/chest wall only (n = 1), supraclavicular nodes (n = 8), and/or internal mammary chain (n = 5). All plans were prescribed to 50 Gy in 25 fractions. The median predicted mean heart dose was 5.1 Gy. Overall, there were no significant differences between the median predicted vs. accumulated LAD doses: mean 10.4 vs. 10.2 Gy, V15 Gy 21% vs. 25%, V30 Gy 0% vs. 1%, max 24.5 vs 25.7 Gy (all p>.05). However, there was a subset of patients (n = 5, 50%) with significant deviations in accumulated vs. predicted dose (at least ±15%). For LAD mean, n = 2 had higher accumulated vs. predicted doses (16.6 vs. 11.6 Gy; 14.6 vs. 12.8 Gy), while n = 3 had lower (21.8 vs. 26.5 Gy; 2.7 vs. 4.2 Gy; 13.9 vs. 16.5 Gy). For LAD V15 Gy, n = 3 had higher accumulated vs. predicted doses (43 vs. 35%; 51% vs. 25%; 14% vs. 9%), while n = 2 had lower (49% vs. 61%; 37% vs. 56%). For LAD V30 Gy, n = 4 had higher accumulated vs. predicted doses (12% vs. 5%; 5% vs. 0%; 4% vs. 0%; 4% vs. 2%), while n = 1 had lower (32% vs. 44%). Daily setup differences, including the extent of inspiratory breath hold, may contribute to deviations in accumulated LAD dose (more than 15% of predicted) in approximately half of patients and were more pronounced in V15 and V30 Gy metrics. The potential for significant LAD dose uncertainty in a clinically meaningful subset of patients should be recognized and warrants further analysis in an expanded cohort.

Effect of Cardiac Rehabilitation on Post Exercise Systolic Blood Pressure Recovery in Patients with Impaired Left Ventricular Ejection Fraction after Recent Myocardial Infarction

Abstract Background Ischemic Heart diseases (IHD) are significant causes of morbidity and mortality worldwide with an estimated 9 million deaths each year. Exercise-based Cardiac Rehabilitation (CR) is one of the most important and cost-effective aspects of secondary prevention in patients with IHD. Post-exercise Systolic Blood Pressure Recovery (SBPR) represents an important hemodynamic parameter that is associated with the risk and severity of ischemic artery disease and future cardiovascular events. Aim of the Work The aim of this study is to assess the effect of CR on post-exercise SBPR in patients with Left Ventricular Ejection fraction less than 45% following a recent Myocardial Infarction. Patients and Methods this study included patients with Left Ventricular Ejection fraction less than 45% following a recent Myocardial Infarction, presenting to Cardiac Rehabilitation Units. the study included two groups of patients. Study group included Patients on optimal medical treatment who are attending CR sessions, and control group included patients on optimal medical treatment who refused or failed to attend more than 50% of cardiac rehabilitation sessions. SBPR was assessed in each patient before and after the CR program. Results When compared to baseline findings, both groups had statistically significant improvement in LVEF, resting SBP, recovery SBP value and HRR. However, CR group had better improvement in LVEF, lower Resting SBP, lower Peak SBP, Better SBP recovery ratio and better HRR outcomes when compared to the changes in the control group. Conclusions Cardiac Rehabilitation after recent Ischemic coronary artery event can provide significant improvement in Systolic blood pressure recovery and heart rate recovery which are important haemodynamic parameters that are associated with the significance and severity of future cardiovascular events. Abbreviations IHD: Ischemic Heart Disease; CR: Cardiac Rehabilitation; LVEF: Left Ventricular Ejection fraction; SBP: Systolic Blood Pressure

Twelve-Month Outcomes of Patients With Myocardial Injury not Due to Type-1 Myocardial Infarction.

Diagnosis of acute myocardial infarction (AMI) requires a combination of elevated cardiac troponins, and clinical or echocardiographic evidence of coronary ischaemia. Identification of patients with a high likelihood of coronary plaque rupture (Type 1 myocardial infarction [MI]) is crucial as it is these patients for whom coronary intervention has been well-established to provide benefit and reduce subsequent coronary ischemic events. However, high-sensitivity cardiac troponin (hs-cTn) assays have increasingly identified patients with hs-cTn elevations not due to Type 1 MI where recommendations for ongoing care are currently limited. Understanding the profile and clinical outcomes for these patients may inform the development of an emerging evidence-base. Using two previously published studies (hs-cTnT study n=1,937, RAPID-TnT study n=3,270) and the Fourth Universal Definition of MI, index presentations of patients to South Australian emergency departments with suspected AMI, defined by high sensitivity cardiac troponin T (hs-cTnT) greater than the upper reference limit (14 ng/L) and without obvious corresponding ischaemia on electrocardiogram (ECG), were classified as either Type 1 MI (T1MI), Type 2 MI (T2MI), acute myocardial injury (AI), or chronic myocardial injury (CI). Patients with non-elevated hs-cTnT (defined as <14 ng/L) were excluded. Outcomes assessed included death, MI, unstable angina, and non-coronary cardiovascular events within 12 months. In total, 1,192 patients comprising 164 (13.8%) T1MI, 173 (14.5%) T2MI/AI, and 855 (71.7%) CI were included. The rate of death or recurrent acute coronary syndrome was greatest in patients with T1MI, but also occurred with moderate frequency in Type 2 MI/AI and CI (T1MI: 32/164 [19.5%]; T2MI/AI: 24/173 [13.1%]; CI:116/885 [13.6%]; p=0.008). Of all the deaths observed, 74% occurred among those with an initial index diagnostic classification of CI. After adjusting for age, gender and baseline comorbidities, the relative hazard ratios for non-coronary cardiovascular readmissions were similar across all groups: Type 2 MI/AI: 1.30 (95% confidence interval 0.99-1.72, p=0.062); CI: 1.10 (95% confidence interval 0.61-2.00, p=0.75). Non-T1MI accounted for the majority of patients presenting with elevated hs-cTnT without ischaemia on ECG. Patients with T1MI had the highest rates of death or recurrent AMI; however patients with T2MI/AI and CI experienced a substantial rate of non-coronary cardiovascular re-hospitalisations.

Clinically significant CYP2C19 genotypes in patients with myocardial infarction in the northern region of Russia

Aim. To determine the associations of allelic variants of the CYP2C19 gene with coronary atherosclerosis and ischemic events in patients with myocardial infarction (MI) living in the Khanty-Mansi Autonomous Okrug — Yugra.Material and methods. This prospective observational study included 203 patients with acute MI who underwent percutaneous coronary intervention. Patients also underwent genetic testing using real-time polymerase chain reaction to determine allelic variants of the CYP2C19 gene. Using biostatistical analysis methods, associations were established between the genotypes of patients with MI, their clinical characteristics and major ischemic events over 7-year follow-up.Results. Significant associations were identified between allelic variants of CYP2C19*2 (*1/*2 and *2/*2) and smoking, right ventricular volume and glomerular filtration rate (GFR). The presence of the allelic variant CYP2C19*3 (*3/*3) was associated with GFR ³90 ml/min/1,73 m2 and impaired glucose tolerance. A significant association was established between the CYP2C19*17 alleles (*1/*17, *17/*17) with coronary atherosclerosis, smoking, levels of troponin T, aspartate aminotransferase, total cholesterol, left ventricular posterior wall thickness, and a history of myocardial infarction. Data from multivariate analysis showed a clear association of allelic variants of CYP2C19*2 (*1/*2 and *2/*2) with the composite endpoint of 7-year follow-up (death, recurrent myocardial infarction, stent/bypass thrombosis, myocardial revascularization). A significant influence of CYP2C19*17 genotypes (*1/*17 and *17/*17) on myocardial revascularization in patients in the post-infarction period was also determined.Conclusion. CYP2C19*2 genotypes (*1/*2 and *2/*2) in MI patients living in Khanty-Mansi Autonomous Okrug — Yugra are clearly associated with ischemic events during a 7-year follow-up. CYP2C19*17 genotypes (*1/*17 and *17/*17) are clearly associated with coronary atherosclerosis and myocardial revascularization in the long-term post-infarction period.

Case of acute recurrent myocardial infarction in a child

Information on the essential aspects of prevalence, etiology and pathogenesis of coronary heart disease, which is the leading cause of death in the world, is given in this article. It is emphasized that the incidence of ischemic coronary events is the result of a complex sequence of pathogenetic links, which involves the formation of atherosclerotic lesions and destabilization as the primary provoking factor. Purpose - the attraction of the medical community attention to the problem of ischemic heart disease in children. A clinical case of recurrent myocardial infarction in a child who was examined and treated at the MNPE «Ivano-Frankivsk Regional Children’s Clinical Hospital of the Ivano-Frankivsk Regional Council», is described here. The key points of the patient’s complaints, anamnesis of life and this disease are described, the data of the objective condition at the hospitalization and during dynamic observation of the child, which showed the signs of left ventricular overload, coronary blood flow disorder, dilatation of the left heart ventricles, decreased left ventricular contractility. The data of the main indices of laboratory and instrumental methods of research, including X-ray diagnostic methods, performed not only on the basis of the department, but also in the Scientific-Practical Medical Center of Pediatric Cardiology and Cardiac Surgery of the Ministry of Health of Ukraine (Kyiv). The treatment of this clinical case in the child is described in this article. The data of dynamic observation are given. The discussion and conclusions emphasize the problem of coronary insufficiency in pediatrics, which requires clinical understanding, the choice of the correct diagnostic algorithm and qualified medical care. The study was performed in accordance with the principles of the Declaration of Helsinki. Informed consent of the child’s parents was obtained for the research conduction. No conflict of interests was declared by the authors.

Association of high-sensitivity troponin T with outcomes in asymptomatic non-severe aortic stenosis: a post-hoc substudy of the SEAS trial

High-sensitivity Troponin T (hsTnT), a biomarker of cardiomyocyte overload and injury, relates to aortic valve replacement (AVR) and mortality in severe aortic stenosis (AS). However, its prognostic value remains unknown in asymptomatic patients with AS. We aimed to investigate if an hsTnT level >14pg/mL (above upper limit of normal 99th percentile) is associated with echocardiographic AS-severity, subsequent AVR, ischaemic coronary events (ICE), and mortality in asymptomatic patients with non-severe AS. In this post-hoc sub-analysis of the multicentre, randomised, double-blind, placebo-controlled SEAS trial (ClinicalTrials.gov, NCT00092677), we included asymptomatic patients with mild to moderate-severe AS. We ascertained baseline and 1-year hsTnT concentrations and examined the association between baseline levels and the risk of the primary composite endpoint, defined as the first event of all-cause mortality, isolated AVR (without coronary artery bypass grafting (CABG)), or ICE. Multivariable regressions and competing risk analyses examined associations of hsTnT level >14pg/mL with clinical correlates and 5-year risk of the primary endpoint. Between January 6, 2003, and March 4, 2004, a total of 1873 patients were enrolled in the SEAS trial, and 1739 patients were included in this post-hoc sub-analysis. Patients had a mean (SD) age of 67.5 (9.7) years, 61.0% (1061) were men, 17.4% (302) had moderate-severe AS, and 26.0% (453) had hsTnT level >14pg/mL. The median hsTnT difference from baseline to 1-year was 0.8pg/mL (IQR,-0.4 to 2.3). In adjusted linear regression, log(hsTnT) did not correlate with echocardiographic AS severity (p=0.36). In multivariable Cox regression, a hsTnT level >14pg/mL vs. hsTnT ≤14pg/mL was associated with an increased risk of the primary composite endpoint (HR, 1.41; 95% CI, 1.18-1.70; p=0.0002). In a competing risk model of first of the individual components of the primary endpoint, a hsTnT level >14pg/mL was associated with ICE risk (HR 1.71; 95% CI, 1.23-2.38; p=0.0013), but not with isolated AVR (p=0.064) or all-cause mortality (p=0.49) as the first event. hsTnT level is within the reference range (≤14pg/mL) in 3 out of 4 non-ischaemic patients with asymptomatic mild-to-moderate AS and remains stable during a 1-year follow-up regardless of AS-severity. An hsTnT level >14pg/mL was mainly associated with subsequent ICE, which suggest that hsTnT concentration is primarily a risk marker of subclinical coronary atherosclerotic disease. Merck & Co., Inc., the Schering-Plough Corporation, the Interreg IVA program, Roche Diagnostics Ltd., and Gangstedfonden. Open access publication fee funding provided by prof. Olav W. Nielsen and Department of Cardiology, Bispebjerg University Hospital, Denmark.

Addition of Risk-enhancing Factors Improves Risk Assessment of Atherosclerotic Cardiovascular Disease in Middle-aged and Older Chinese Adults: Findings from the Chinese Multi-provincial Cohort Study

Objective: This study aimed to examine whether integrating risk-enhancing factors into the Chinese Society of Cardiology-recommended clinical risk assessment tool (i.e., the CSC model) for atherosclerotic cardiovascular disease (ASCVD) might improve 10-year ASCVD risk stratification in Chinese adults. Methods: A total of 4910 Chinese participants who were 50–79 years of age and free of cardiovascular disease in the 2007–2008 Survey from the Chinese Multi-provincial Cohort Study were included. We assessed the updated model’s clinical utility (i.e., Harrell’s C-index and net reclassification improvement [NRI]) by adding risk-enhancing factors individually or the number of risk-enhancing factors to the CSC model, for all individuals or those at intermediate risk. Risk-enhancing factors, including a family history of CVD, triglycerides ≥2.3 mmol/L, high-sensitivity C-reactive protein ≥2 mg/L, Lipoprotein (a) ≥50 mg/dL, non-high-density lipoprotein cholesterol ≥4.9 mmol/L, overweight/obesity, and central obesity, were evaluated. ASCVD events were defined as a composite endpoint comprising ischemic stroke and acute coronary heart disease events (including nonfatal acute myocardial infarction and all coronary deaths). Results: During a median 10-year follow-up, 449 (9.1%) ASCVD events were recorded. Addition of ≥2 risk-enhancing factors to the CSC model yielded a significant improvement in the C-index (1.0%, 95% confidence interval [CI]: 0.2–1.7%) and a modest improvement in the NRI (2.0%, 95% CI: −1.2–5.4%) in the total population. For intermediate-risk individuals, particularly individuals at high risk of developing ASCVD, significant improvements in NRI were observed after adding ≥2 risk-enhancing factors (17.4%, 95% CI: 5.6–28.5%) to the CSC model. Conclusions: Addition of ≥2 risk-enhancing factors refined 10-year ASCVD risk stratification, particularly for intermediate-risk individuals, supporting their potential in helping tailor targeted interventions in clinical practice.

High-sensitive Troponin T is not associated with the progression of asymptomatic mild to moderate aortic stenosis: a post hoc substudy of the SEAS trial

Abstract Background Aortic stenosis (AS) and coronary artery disease (CAD) share pathophysiological pathways, as reflected by frequent concomitant revascularization in patients undergoing aortic valve replacement (AVR). High-sensitive Troponin T (hsTnT) is a proven biomarker of cardiomyocyte overload and injury, and predicts postoperative mortality after AVR. However, it is unknown if hsTnT can predict AVR, mortality or ischemic coronary events (ICE) in asymptomatic AS patients. Purpose To investigate the hypothesis that increased hsTnT is associated with more severe AS and a higher risk of adverse outcomes in asymptomatic AS patients without overt CAD. Methods hsTnT concentrations were examined at baseline and after 1-year follow-up in 1739 asymptomatic AS patients enrolled in the randomized, double-blind Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. The main inclusion criteria were: left ventricular (LV) ejection fraction &amp;gt;55%, transaortic maximal velocity between 2.5–4.0 m/s, and no history of CAD. The primary exposure variable was increased hsTnT (&amp;gt;14 pg/mL according to the assay manufacturer, Roche). This study's primary endpoint was a composite of competing risk outcomes: all-cause mortality as the first event, AVR without revascularization, and ICE (defined as myocardial infarction before AVR, PCI before or combined with AVR, or any CABG). Multivariable regression examined associations between hsTnT and clinical variables. Cox proportional hazards regression models were adjusted for age, sex, creatinine, LV mass index, mean aortic pressure gradient (Pmean) and stratified by center and lipid-lowering treatment. We analyzed outcomes during 5-year follow-up from baseline. Results At baseline, 453 (26.0%) patients had increased hsTnT and 302 (17.4%) had moderate-severe AS with a mean (SD) aortic valve area of 0.8 (0.2) cm2 and Pmean of 33.2 (8.8) mmHg. The median annual hsTnT change from baseline to year 1 was 0.8 pg/mL (IQR, −0.4 to 2.3), regardless of AS severity (P=0.08). In adjusted models, log(hsTnT at baseline) was associated with age, sex, creatinine, and LV mass index (all P&amp;lt;0.05), but not with AS severity (P=0.36). The incidence rate ratio for ICE (Figure 1) in patients with increased vs normal baseline hsTnT concentrations was 2.32 (95% CI, 1.72–3.11, P&amp;lt;0.001). In adjusted Cox regression, increased hsTnT was associated with an increased 5-year ICE risk (HR 1.64; 95% CI, 1.18–2.29, P=0.003), but neither with AVR without revascularization nor death (Figure 1). Conclusion In these asymptomatic AS patients without overt CAD, hsTnT is often normal and remains stable during 1 year of follow-up regardless of AS severity. Increased hsTnT is associated with CAD-related events, but neither to AS severity nor AVR without concomitant revascularization. This analysis does not support routine hsTnT measurement in asymptomatic AS to predict AVR related to AS progression, although hsTnT could improve the risk assessment for ICE. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Main sponsor (SEAS): Merck &amp; Co Inc, Whitehouse Station, New JerseyBlood analysis sponsor: Roche Diagnostics International Ltd, Switzerland

Lipoprotein(a) and the Risk for Coronary Heart Disease and Ischemic Stroke Events Among Black and White Adults With Cardiovascular Disease.

BackgroundIt is unclear whether lipoprotein(a) is associated with coronary heart disease (CHD) and ischemic stroke events in White and Black adults with atherosclerotic cardiovascular disease (ASCVD).Methods and ResultsWe conducted a case‐cohort analysis, including Black and White REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants ≥45 years of age with prevalent ASCVD (ie, CHD or stroke) at baseline between 2003 and 2007. Baseline lipoprotein(a) molar concentration was measured in participants with ASCVD who experienced a CHD event by December 2017 (n=1166) or an ischemic stroke by September 2019 (n=492) and in a random subcohort of participants with prevalent ASCVD (n=1948). The hazard ratio (HR) for CHD events per 1 SD (1.5 units) higher log‐transformed lipoprotein(a) was 1.26 (95% CI, 1.02–1.56) among Black participants and 1.16 (95% CI, 1.02–1.31) among White participants (P value comparing HRs, 0.485). The HR for CHD events per 1 SD higher log‐lipoprotein(a) within subgroups with hs‐CRP (high‐sensitivity C‐reactive protein) ≥2 and <2 mg/L was 1.31 (95% CI, 0.99–1.73) and 1.23 (95% CI, 0.85–1.80), respectively (P value comparing HRs, 0.836), among Black participants, and 1.07 (95% CI, 0.91–1.27) and 1.36 (95% CI, 1.10–1.70), respectively (P value comparing HRs, 0.088), among White participants. There was no evidence that the association between lipoprotein(a) and CHD events differed by statin use. There was no evidence of an association between lipoprotein(a) and ischemic stroke events among Black or White participants.ConclusionsHigher lipoprotein(a) levels were associated with an increased risk for CHD events in Black and White adults with ASCVD.

1-year outcomes results of coronary artery bypass grafting in patients with target artery distal calcinosis

Aim. Comparative assessment of the surgical strategies and one-year results of coronary artery bypass grafting (CABG) in patients with and without target artery distal calcinosis.Methods. A prospective study from January 2017 to October 2018 included 462 patients with coronary artery disease. All patients underwent CABG. Groups were formed according to coronary angiography data. Group 1 — patients with target artery distal calcinosis (n = 108). Group 2 — patients without any marks of coronary calcification (n = 354). To minimize systematic errors and maximize their comparability, computer correction was performed using propensity score matching (group 1, n = 106, group 2, n = 106). Intraoperative data and one-year outcomes were analyzed and compared.Results. Following the strategy for complete revascularization, we had to form a greater number of distal anastomosis in group 1 due to severe coronary atherosclerosis. The index of revascularization was higher in group 1 (4.4 ± 0.7 and 3.9 ± 0.8, p = 0.001). We registered a higher frequency of using prolonged patch-angioplasty (21.7 versus 1.8 %, p &lt; 0.001), anastomosis with artery diameter &lt; 1.5 mm (33.9 versus 16 %, p &lt; 0.003), coronary artery endarterectomy (13.2 versus 0.9%, p &lt; 0.001) in patients with coronary artery calcinosis. As well as the creation of composite grafts, such as Y-graft (33 versus 8.5 %, p &lt; 0.001) and sequential graft (13.9 versus 5.7 %, p = 0.03) were higher in group 1. The use of adjunctive surgical techniques in the main group significantly increased the duration of cardio-pulmonary bypass and aortic cross-clamp time. The primary endpoints – coronary ischemic events – angina recurrence (10.3 versus 6.3 %, p = 0.307), myocardial infarction (3.1 versus 2.1 %, p = 0.654), the need for re-revascularization (3.1 versus 1 %, p = 0.318) were comparable in 1 year after surgery. Overall mortality was relatively low in both groups.Conclusion. CABG in patients with target artery distal calcinosis is associated with similar one-year outcomes compared to CABG in patients without coronary artery calcification. The positive results of CABG in patients with target artery distal calcinosis indicate the benefits of complete myocardial revascularization, despite the long duration and complexity of interventions. Received 29 September 2021. Revised 20 October 2021. Accepted 22 October 2021. Funding: The work was carried out within the framework of the state assignment (No. AAAA-A18-118022290040-7). Conflict of interest: Authors declare no conflict of interest. Contribution of the authors:Conception and study design: A.A. Shiryaev, G.B. Mayorov, D.M. GalayutdinovData collection and analysis: G.B. Mayorov, S.K. Kurbanov, V.Yu. ZaikovkiiStatistical analysis: S.K. Kurbanov, G.B. MayorovDrafting the article: G.B. Mayorov, A.V. Andreev, S.K. KurbanovCritical revision of the article: R.S. Akchurin, A.A. Shiryaev, D.M. Galayutdinov, V.P. VasilievFinal approval of the version to be published: R.S. Akchurin, A.A. Shiryaev, D.M. Galayutdinov, V.P. Vasiliev, S.K. Kurbanov, A.V. Andreev, V.Yu. Zaikovkii, G.B. Mayorov

Nine-Year Experience With the Arterial Switch Operation With Closed Coronary Transfer

BackgroundCoronary artery transfer is a critical step of the arterial switch operation (ASO) for transposition of the great arteries (TGA). Strategies for coronary transfer include open transfer before neoaortic anastomosis and closed transfer after neoaortic anastomosis. This study reports outcomes of ASO with closed coronary transfer at a single institution. MethodsA retrospective analysis was performed of patients undergoing ASO for TGA from November 2006 to September 2015. Closed coronary transfer was universally employed. Patients were assigned to simple vs complex coronary anatomy groups. The primary outcome was overall survival. Secondary outcomes included reoperation-free survival, coronary reintervention, and aortic insufficiency. ResultsNinety-six consecutive patients underwent ASO for TGA. Median follow-up was 5.8 years. Thirty-five (36%) patients had complex coronary anatomy, which was associated with significantly longer cardiopulmonary bypass and aortic cross-clamp time. Overall survival was 97.4%, and reoperation-free survival was 83.6%. There was no difference in survival or reoperation-free survival of patients with simple vs complex coronary anatomy. Hispanic ethnicity, side-by-side great arteries, and urgent or emergent operation were significantly associated with the composite outcome of reoperation or mortality. There were no coronary interventions after ASO, and the incidence of moderate or greater aortic insufficiency was 2.1% at hospital discharge and 1.5% in follow-up. ConclusionsClosed coronary transfer during ASO has excellent short-term and midterm results. Despite variable and often complex coronary anatomy, coronary ischemic events after ASO are avoidable. Closed coronary transfer has a low risk of aortic valve injury or insufficiency.

Prediction of clinical course in patients with diffuse coronary artery disease after coronary bypass surgery

Aim. To determine the incidence, predictors and develop a model for long-term risk stratification of ischemic events in patients with coronary artery disease after coronary bypass surgery.Material and methods. This retrospective study of the clinical course in patients with diffuse coronary artery disease (CAD) after coronary endarterectomy and bypass grafting surgery. A total of 232 patients were included, while long-term outcomes were assessed in 202 patients. Among them, complete data on clinical status were obtained from survivors (n=191). The median follow-up was 60 (interquartile range, 42; 74) months, while the minimum follow-up — 12 months, the maximum was 96 months. The primary composite endpoint reflecting the unfavorable course of CAD included coronary ischemic events (recurrent angina, myocardial infarction, repeat revascularization), while secondary endpoint — allcause mortality. The factors influencing the development of primary and secondary endpoints were studied.Results. An unfavorable CAD course was diagnosed in 39 patients (20,4%), while 11 deaths were recorded (5,4%). Univariate analysis demonstrated a significant role of prior myocardial infarction in the increase in mortality rate (p=0,029). Among the factors influencing the CAD course, no significant differences were obtained for any of them. A multivariate analysis was performed to identify a high-risk group for an unfavorable course of diffuse CAD. Independent predictors were identified, the most significant contribution of which was made by multifocal atherosclerosis (odds ratio (OR)=1,99, 95% confidence interval (CI), 0,93-4,21, p=0,072), low adherence to secondary prevention measures (OR=2,21, 95% CI, 0,86-6,89, p=0,128) and diabetes (OR=1,73, 95% CI, 0,79-3,72, p=0,162). Using the results obtained, a prognostic model with high specificity (64%) and moderate sensitivity (53%) was created.Conclusion. The highest probability of an unfavorable long-term course of diffuse CAD was noted in patients with diabetes, multifocal atherosclerosis, and low adherence to secondary prevention measures. The obtained results make it possible to identify a high-risk group in this cohort of patients, determine the reserve of secondary prevention measures and a direction of actions to improve outcomes.

Risk scores in predicting adverse events after an acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Introduction ST-segment elevation myocardial infarction (STEMI) is a serious event that usually occur in patients with cardiovascular risk factors and is associated with great morbidity and mortality. PARIS ischemic risk score and TIMI score were validated to evaluate ischemic risk in STEMI patients who underwent percutaneous coronary intervention (PCI) and to estimate mortality, respectively. Despite these specific purposes, the usefulness of these scores in predicting adverse cardiovascular events (ACE) is unknown. Objectives To assess the prognostic value of PARIS and TIMI scores for cardiovascular events, coronary ischemic events and mortality in patients after STEMI. Methods Retrospective single center cohort study enrolled 103 patients with STEMI diagnosis between 2018 and 2019, during a mean follow-up period 30.30 ± 6.46 months and patients were included regardless of the reperfusion strategy. Primary endpoint (PE) was a composite of acute coronary events (ACE), admissions to the emergency department by heart failure (HF) decompensation or chronic coronary syndrome and HF hospitalization. Secondary endpoint (SE) was ACE. Cardiovascular and non-cardiovascular death was determined. PARIS ischemic risk score was calculated and patients were stratified into low (0-2), intermediate (3-4) or high (≥ 5) ischemic risk categories. TIMI score was also assessed. Results Out of 103 patients with STEMI diagnosis, the median age was 58.15 ± 12.6 years and 85,4% were male. Fifty-seven patients (55.3%) had hypertension, 45 (43.7%) dyslipidemia, 18 (17.5%) diabetes, 17 (15.5%) were obese and seventy-eight patients (75.7%) had history of smoking. Twenty (19.4%) patients had a previous acute coronary syndrome and 15 underwent PCI. Twenty-five (24.3%) patients were included in low PARIS ischemic risk category, 53 (51.5%) in intermediate risk and 20 (19.4%) in high risk category. PE occurred in 16 patient (15.5%) and SE in 7 patients (6.8%). Eight patients died during the follow-up period (7.8%), 4 of cardiovascular causes (50%), 3 of non-cardiovascular causes (37.5%) and 1 of unknown cause. PARIS ischemic risk score showed prognostic value for PE, with an area under the curve (AUC) of 0.65, 95% confidence interval (CI) 0.506-0.806 and p-value 0.039. PARIS score also had predictive value for SE (AUC 0.816, 95% CI 0.604-1.000; p 0.004) as well as TIMI score (AUC 0.738, 95% CI 0.560 – 0.917; p 0.032). Both scores showed a good prognostic value in evaluating all-cause mortality, with a slightly better predictive value for TIMI score (AUC 0.91, 95% CI 0.802 – 1.00) when compared to PARIS score (AUC 0.84, 95% CI 0.685 – 0.987). Conclusion This study revealed that PARIS and TIMI scores have a good discriminatory power to predict prognosis in STEMI patients. According to our study results, these scores could be an interesting tool to determine the likelihood of fatal and non-fatal outcomes, including ACS.

Comparison of risk factors for ischemic stroke and coronary events in a population-based cohort

BackgroundAlthough coronary events (CE) and ischemic stroke share many risk factors, there are also some important differences. The aim of this paper was to assess the association of risk factors in relation to incident CE and ischemic stroke and to evaluate the heterogeneity in patterns of risk factors between the two outcomes.MethodTraditional risk factors and inflammatory markers associated with coronary events and ischemic stroke were measured in the Malmö Diet and Cancer Cohort (MDCS, n = 26 519), where a total of 2270 incident ischemic stroke and 3087 incident CE occurred during a mean follow up time 19 ± 6 years, and in relation to inflammatory markers in the cardiovascular sub-cohort (MDC-CV, n = 4795). Cox regression analysis was used to obtain hazard ratios. A modified Lunn-McNeil competing risk analysis was conducted to assess the significance of any differences in risk profiles of these outcomes.ResultsMost cardiovascular risk factors were associated both with incident CE and ischemic stroke. However, current smoking, ApoB, low ApoA1, male sex and education level of ≤ 9 years of schooling were preferentially associated with CE compared to ischemic stroke. Conversely, age showed a stronger association with ischemic stroke than with CE.ConclusionCE and ischemic stroke have broadly similar risk factors profiles. However, there are some important differential associations, as well as substantial differences in the magnitude of the association. These could reflect the distinct biology of atherogenesis in different vascular beds. The difference in the determinants highlights the importance of looking at CE and ischemic stroke, two manifestations of cardiovascular disease, separately.