Advanced Coronary Artery Disease Research Articles

The Utility of Pre-Procedural Blood Tests in Neuraxial Blocks: A Retrospective Study in High-Risk Patients

Background/Objectives: The necessity and clinical utility of routine pre-procedural blood tests (PBTs) before neuraxial blockade remain controversial. This study evaluates the effectiveness of PBTs in identifying clinically significant conditions in an outpatient setting. Methods: This single-center retrospective study involved patients who received neuraxial blockades from January 2020 to August 2023. We extracted medical information and laboratory data from the electronic medical records during the pre-procedural period. Through a multivariate regression analysis, we identified patient factors associated with abnormal laboratory results. Results: Advanced age (OR, 1.021; p = 0.026) and a history of cancer (OR, 2.359; p = 0.016) were significantly associated with elevated CRP levels (>0.30 mg/dL). Severe hyperglycemia (≥200 mg/dL) was found in 24 patients (3.88%), with a history of cancer being a strong predictor (OR, 6.764; p < 0.001). No significant abnormalities were observed in PT or PTT. Reduced eGFR (<60 mL/min/1.73 m2) was detected in 8.62% of patients, despite no prior history of renal dysfunction. A multivariate analysis revealed that advanced age, hypertension, cancer, and coronary artery disease were significant predictors of abnormal PBT results, highlighting the importance of selective testing in high-risk patients. Conclusions: Routine PBTs are not universally required for all patients undergoing neuraxial blockade but can provide crucial information in high-risk populations. A selective testing approach based on individual risk factors is recommended to optimize patient safety and resource utilization. Future studies should aim to establish clear guidelines for targeted PBT use.

Abstract 4115015: Hyperpolarized Carbon-13 Metabolic Imaging Detects Changes in Cardiac Mitochondrial Metabolism in Patients Before and After Coronary Artery Bypass Graft Surgery

Background: Coronary Artery Disease (CAD) is a significant global health issue, necessitating improved diagnostic tools for visualizing cardiac energetics. Traditional imaging methods such as PET and dobutamine stress echocardiography do not directly assess mitochondrial metabolism. Hyperpolarized Carbon-13 metabolic magnetic resonance imaging (HP- 13 C MRI) offers a promising non-invasive method for investigating mitochondrial function in CAD. This study utilizes HP- 13 C MRI to detect changes in mitochondrial metabolism in patients undergoing Coronary Artery Bypass Graft (CABG) surgery (Fig.1). Methods: We conducted HP- 13 C MRI examinations on two patients with advanced CAD before and (~4-6 months after CABG surgery and one healthy subject (Fig. 2 A,B). Participating subjects provided informed consent according to a protocol approved by the Institutional Review Board and Protocol Review Committee. Baseline blood samples were analyzed for pyruvate, triglycerides, free fatty acids, and insulin levels. Post-glucose load, patients received an intravenous injection of an IND-approved metabolic probe, [1- 13 C] pyruvic acid, prepared under Good Manufacturing Practice regulations. The HP solution was administered after polarization in a clinical polarizer (SPINlab™, GE Healthcare). Imaging was performed using a GE MR750 MR system with a Helmholtz loop-pair 13 C coil (PulseTeq Limited, UK). Data were reconstructed and analyzed with MATLAB scripts. Results and Discussion: Baseline blood measurements were normal for the healthy subject, but those with advanced CAD showed variable and abnormal values (Fig. 2C). HP- 13 C MRI safely assessed cardiac metabolism in patients with advanced CAD. Patients with advanced CAD exhibited reduced pyruvate metabolism compared to healthy controls, shown by lower myocardial bicarbonate/(bicarbonate+lactate) ratios (Bic/(Bic+Lac)). Following CABG, only Patient 2 showed improved Bic/(Bic+Lac), while Patient 1 did not (Fig. 3A-B). This variability may be influenced by differences in nutrition, hormonal status, medication regimens, or other factors. Changes in % Bic/(Bic+Lac) across different coronary artery segments were observed post-CABG in CAD patients (Fig. 3C). Conclusion: HP- 13 C MRI non-invasively assesses cardiac metabolism in CAD patients, demonstrating the potential to evaluate post-CABG metabolic changes. Our efforts continue to recruit large cohort to understand individual variability.

Clinical Impact of Sarcopenia Screening on Long-Term Mortality in Patients Undergoing Coronary Bypass Grafting.

Sarcopenia is an aging-related condition characterized by loss of skeletal muscle mass and is an indicator of subclinical atherosclerosis. The relationship between reduced muscle mass and long-term clinical outcomes in patients with advanced coronary artery disease who have undergone coronary artery bypass grafting (CABG) is not fully understood. This study is sought to evaluate the prognostic implications of sarcopenia screening in patients undergoing CABG. A total of 2810 patients who underwent CABG were analysed and classified according to presence of reduced muscle mass. The skeletal muscle index (SMI) was calculated as L3 muscle area (cm2)/height (m)2 on computed tomography. Reduced SMI was defined as SMI ≤ 45 cm2/m2 in male and ≤ 38 cm2/m2 in female. The primary outcome was all-cause mortality, and survival analysis was performed using the Kaplan-Meier method and compared with the log-rank test. The median follow-up was 8.7 years, and 924 patients (32.9%) had reduced SMI. Patients with reduced SMI were older (67.7 ± 8.8 vs. 62.2 ± 9.8 years; p < 0.001) and less frequently male (69.8% vs. 81.1%; p < 0.001). SMI was significantly associated with risk of death on a restricted cubic spline curve (HR = 1.04 per-1 decrease; 95% CI 1.03-1.05; p < 0.001). Patients with reduced SMI had a higher incidence of long-term mortality than those with preserved SMI (survival rate 41.4% vs. 62.8%; HRadj = 1.18, 95% CI 1.03-1.36, p = 0.020). Subgroup analysis showed that the prognostic implication of reduced SMI on long-term survival was more evident in male (HRadj = 2.01, 95% CI 1.72-2.35) than female (HRadj = 1.28, 95% CI 0.98-1.68) (interaction p = 0.006). Reduced muscle mass, defined by SMI on computed tomography, was associated with long-term mortality after CABG. These results provide contemporary data to allow the evaluation of physical frailty in patients with advanced coronary artery disease before surgery. Long-Term Outcomes and Prognostic Factors in Patients Undergoing CABG or PCI: NCT03870815.

A novel stent flow chamber system demonstrates reduced thrombogenicity of bioresorbable magnesium scaffolds

Coronary artery disease (CAD) is characterized by narrowing and subsequent blockade of coronary arteries, and imposes a significant health and economic burden. Stent and scaffold devices are introduced in advanced CAD to improve vascular stability and restore blood flow. Although in vitro flow systems like the Chandler loop have been developed to enhance the understanding of interactions between device materials, their coatings, and vascular cells, imaging-based in vitro analysis of device performance is limited. In this study, we established a novel stent flow chamber system designed to assess the thrombogenicity of bioresorbable magnesium scaffold (RMS) and stent materials in vitro. Additionally, we compared the thrombogenicity – an important clinical parameter in stent performance – of the Magmaris-316 L stainless steel stent with its predecessors, Magmaris RMS and a prototype of the third-generation RMS (DREAMS 3G). Analysis of platelet adhesion and coverage of the different devices under flow conditions demonstrated that the Magmaris RMS exhibits reduced thrombogenicity compared to the Magmaris-316 L stainless steel stent. Moreover, thrombogenicity of the DREAMS 3G prototype, composed of BIOmag material, is further decreased compared to its predecessors. The observed reduction in thrombogenicity of the DREAMS 3G prototype in vitro suggests additional improvements in clinical safety and efficacy, highlighting its promise for treating CAD. Future research on this prototype may thus open avenues for analyzing other blood components and patient-derived endothelial cells. In line with the 3R principles, this approach may also help reduce the need for animal testing.

Long-Term Impacts of Complete Revascularization on Clinical Outcomes in Patients with Coronary Chronic Total Occlusion

The impact of complete revascularization (CR), achieved through the recanalization of coronary chronic total occlusions (CTOs), on long-term patient outcomes remains uncertain.To evaluate this in patients who achieved CR after CTO-PCI with those who did not due to deferred CTO-PCI, the Asan Medical Center Registry was reviewed to identify coronary artery disease (CAD) patients with CTOs treated between January 2003 and December 2018. Patients were included with single-vessel disease with CTO and with multivessel disease who had undergone revascularization for non-CTO lesions. These subjects were divided into those who achieved CR with CTO-PCI and those who did not due to deferred CTO-PCI. Their outcomes were compared following 1:1 propensity score matching. Of the 2,746 enrolled CAD patients with CTOs, 1,837 achieved CR with CTO-PCI and 909 did not. Propensity score matching yielded 653 patient pairs. The CR-achieving group had a significantly lower 10-year risk of the primary composite outcome of death, myocardial infarction, stroke, or repeat revascularization (hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.46–0.72; P < 0.001), as well as significantly lower risks of death (HR: 0.66; 95% CI: 0.51–0.87; P = 0.003) and repeat revascularization (HR: 0.67; 95% CI: 0.48–0.95; P = 0.023). CR was beneficial in all subgroups, including patients with major cardiovascular risk factors such as older age, hypertension, diabetes, and advanced CAD. Compared with incomplete revascularization, CR may significantly reduce the 10-year incidence of major adverse cardiac events in patients with CTO.

High-dose atorvastatin and rosuvastatin reduce the levels of neutrophil extracellular trap-related proteins in coronary artery disease: association with prothrombotic state.

Neutrophil extracellular trap (NET) formation is involved in atherothrombosis. We sought to investigate whether statins affect neutrophil extracellular traps activation and release (NETosis) in coronary artery disease (CAD), and whether such changes show associations with statin‑induced additional effects. We studied 130 patients with advanced CAD before and at least 6 months after initiation of high‑dose statin therapy with rosuvastatin 40 mg/d or atorvastatin 80 mg/d. The levels of circulating citrullinated histone H3 (H3cit), myeloperoxidase (MPO), and neutrophil elastase (NE) were assessed as proteins associated with NETosis along with thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis inhibitors. Following statin therapy intensification, we observed reduced accumulation of H3cit (-30.4%), MPO (-28.1%), and NE (-25.5%; all P <0.001), all not associated with low‑density lipoprotein cholesterol (LDL‑C) lowering (-25%). However, H3cit level was lower in 50 patients (38.5%) who achieved the target LDL‑C below 1.8 mmol/l (-16.5%; P = 0.004), and in 19 patients (14.6%) with LDL‑C below 1.4 mmol/l (-25.5%; P = 0.001), as compared with the remaining individuals. The reductions in H3cit and MPO levels were associated with a 42.9% decrease in C‑reactive protein (CRP) level on high‑dose statins (R = 0.855; P <0.001 and R = 0.25; P = 0.004, respectively), along with increases in Ks and reduction in thrombin activatable fibrinolysis inhibitor (TAFI) activity, but not with CLT or thrombin generation (all |R|, 0.24-0.4; P <0.01). In multivariable analysis, changes in CRP (β = 0.771; P <0.001), TAFI activity (β = 0.125; P = 0.013), and fibrinogen level (β = 0.106; P = 0.034) were independently associated with a decrease in H3cit concentration. We showed for the first time that high‑dose statins can reduce the level of NET‑related proteins in association with anti‑inflammatory and antithrombotic actions in CAD patients.

Clinical impact of Sarcopenia on long-term mortality in patients undergoing coronary bypass grafting

Abstract Background Sarcopenia is an aging-related condition characterized by loss of skeletal muscle mass and is an indicator of subclinical atherosclerosis. The relationship between sarcopenia and long-term clinical outcomes in patients with advanced coronary artery disease who have undergone coronary artery bypass grafting (CABG) is not fully understood. This study aimed to evaluate the prognostic implications of sarcopenia in patients undergoing CABG. Methods A total of 2,810 patients who underwent CABG were derived from the Samsung Medical Center institutional registry from 2007 to 2017 and classified according to the presence of sarcopenia. The skeletal muscle index (SMI) was calculated as L3 muscle area (cm2)/height (m)2 on computed tomography. Sarcopenia was defined as SMI ≤45 cm2/m2 in men and ≤38 cm2/m2 in women. The primary outcome was all-cause mortality during follow-up. Results The median follow-up was 8.7 years, and 924 patients (32.9%) had sarcopenia. Patients with sarcopenia were older and more frequently women. SMI was significantly correlated with age (R=-0.34, P&amp;lt;0.001), weight (R=-0.56, P&amp;lt;0.001), and body mass index (R=-0.52, P&amp;lt;0.001). SMI was significantly associated with risk of death on a restricted cubic spline curve (HR=1.04 per-1 decrease, 95% CI 1.03-1.05, P&amp;lt;0.001). Patients with sarcopenia had a higher incidence of long-term mortality than those without sarcopenia (survival rate 41.4% vs. 62.8%; adjusted HR=1.18, 95% CI 1.03-1.36, P=0.02). Subgroup analysis showed that the prognostic implication of sarcopenia on long-term survival was more evident in men (adjusted HR=2.01, 95% CI 1.72-2.35) than women (adjusted HR=1.28, 95% CI 0.98-1.68) (interaction P=0.006). Conclusions Sarcopenia, defined by SMI on computed tomography, was associated with long-term mortality after CABG. These results provide contemporary data to allow the evaluation of physical frailty in patients with advanced coronary artery disease before surgery.

Lipoprotein(a) regulates vascular redox state and inflammatory response in patients with coronary artery disease

Abstract Background Circulating Lipoprotein(a) (Lp(a)) is associated with cardiovascular disease, and over 90% of its variation in plasma is genetically determined. However, neither the causal nature of this association nor the underlying mechanisms are fully documented. Purpose We explored the hypothesis that Lp(a) triggers atherogenesis by dysregulating vascular redox-sensitive inflammatory state. Methods 1027 patients with advanced coronary artery disease (CAD) undergoing cardiac surgery were genotyped and a genetic signature (LPA) determining Lp(a) levels was generated. RNA-sequencing and vascular superoxide (O2.-) measurements were performed in internal mammary arteries (IMA), and the contribution of NADPH-oxidases and uncoupled endothelial nitric oxide synthase (eNOS) were determined. Patients were followed up for a median of 5.07 years. Results A genetic screening identified 7 SNPs (LPA) that were associated with increased Lp(a) plasma levels (A). Patients in the alternative LPA variant group, as well as patients with higher plasma Lp(a) levels, had significantly higher basal arterial O2.-. Patients with diabetes had significantly lower plasma Lp(a) compared to non-diabetics and the association between plasma Lp(a) and arterial O2.- was driven by non-diabetic patients. The effect of Lp(a) on vascular redox state was primarily due to eNOS uncoupling, resulting from reduced vascular tetrahydrobiopterin (BH4) bioavailability. Indeed, patients in the alternative LPA variant group or with higher plasma Lp(a) levels had a greater arterial eNOS-derived (LNAME-inhibitable) O2.- production (B,C). Levels of eNOS essential cofactor BH4 (defined by the ratio of plasma BH4 to its oxidation product BH2) were lower in patients with higher plasma Lp(a) levels (D). There was no significant impact of Lp(a) variability on vascular NADPH oxidase-derived O2.-. RNA sequencing of arterial tissue revealed dysregulation of nitrosative and inflammatory signalling in patients with high Lp(a), although there was no association with systemic biomarkers of inflammation (i.e. hsCRP) or oxidative stress (i.e. malondialdehyde). Finally, both LPA and high plasma Lp(a) were associated with elevated risk for cardiovascular mortality (E,F). When the cox regression models were additionally corrected for arterial O2.- production, both the models for the LPA genetic signature (HR[95% CI]=2.053[0.180-23.428], p=0.563) and plasma Lp(a) (HR[95% CI]=1.700[0.325-8.885], p=0.529) lost significance. This implies that redox-sensitive inflammatory signalling may be a link between Lp(a) and cardiovascular risk. All above associations were independent from plasma ApoB. Conclusions This study demonstrates for the first time that a genetically determined increase in plasma Lp(a) results in dysregulated vascular redox/nitrosative signalling in patients with atherosclerosis, revealing new therapeutic opportunities in cardiovascular prevention.

Prognostic value of quantitative anatomical and functional measures of coronary artery disease in diabetic and non-diabetic patients

Abstract Background Diabetes is associated with increased risk of coronary artery disease (CAD). However, the relative prognostic importance of anatomical and functional findings of CAD in the presence vs. absence of diabetes is incompletely understood. Technological advances have made quantitative analysis of coronary artery plaques and stenosis feasible by coronary computed tomography angiography (CTA). In turn, positron emission tomography (PET) enables absolute quantification of myocardial blood flow (MBF). Purpose To study long-term prognostic value of quantified severity of coronary atherosclerosis and myocardial perfusion in non-diabetic vs. diabetic patients with suspected CAD. Methods From two academic medical centres, we identified symptomatic patients with suspected CAD who had undergone coronary CTA and [15O]H2O PET myocardial perfusion imaging during adenosine stress. Based on artificial intelligence -guided quantitative analysis of coronary CTA scans, the anatomical severity of CAD was measured as the presence of obstructive CAD (≥50% diameter stenosis) and percent atheroma volume (PAV; higher vs. lower than median). The functional severity of CAD was measured as the presence of regional myocardial ischemia (≥2 adjacent segments with stress MBF &amp;lt;2.3 ml/g/min) and global stress MBF (&amp;lt;2.2 ml/g/min vs. ≥ 2.2 ml/g/min) by PET. Annual rates of adverse events (AER) including all-cause mortality, myocardial infarction (MI), and unstable angina pectoris (UAP) were evaluated. Results Among 1311 patients, 251 (19%) had diabetes. Patients with diabetes had more frequently obstructive CAD (55% vs. 43%, p&amp;lt;0.001) and regional myocardial ischemia (51% vs. 43%, p=0.015), higher plaque burden by PAV (12% vs. 7%, p&amp;lt;0.001), and lower global stress MBF (2.78 ml/g/min vs. 3.05 ml/g/min, p&amp;lt;0.001). During median follow-up of 7.1 years, 171 (13.0%) patients experienced AE (85 deaths, 56 MIs, and 30 UAPs). Patients with diabetes had higher AER than non-diabetic patients (3.1% vs. 1.6%, p&amp;lt;0.001). The presence of obstructive stenosis was associated with increased AER in non-diabetic (2.6% vs. 1.0%, p&amp;lt;0.001) and diabetic patients (4.2% vs. 1.9%, p&amp;lt;0.001). High plaque burden by PAV was associated with increased AER in non-diabetic (2.8% vs. 0.7%, p&amp;lt;0.001) and diabetic patients (3.9% vs. 1.7%, p&amp;lt;0.001). The presence of regional myocardial ischemia was associated with increased AER in non-diabetic (2.5% vs. 1.1%, p&amp;lt;0.001), but not in diabetic patients (3.4% vs. 2.7%, p=0.238). Low global stress MBF was associated with increased AER in non-diabetic (2.9% vs. 1.3%, p&amp;lt;0.001), but not among diabetic patients (3.2% vs. 3.0%, p=0.286). Conclusions Diabetes was associated with more advanced CAD. Quantified severity of anatomical findings predicted long-term adverse outcome in non-diabetic and diabetic patients. In contrast, functional imaging risk stratified non-diabetic patients, whereas diabetic patients had impaired long-term outcome irrespective of perfusion findings.

Association of the lipoprotein(a) gene (LPA) p.Ile4399Met variant with lipoprotein(a) level and cardiovascular events in patients following coronary artery bypass grafting under 65 years of age

Abstract Introduction Lipoprotein(a) (Lp[a]), a well-known risk factor for atherosclerotic cardiovascular disease, is largely determined by variation in the Lp(a) gene (LPA) locus encoding apolipoprotein(a). The LPA gene Ile4399Met (rs3798220) variant has been previously reported to have a strong association with the Lp(a) level in patients with coronary artery disease (CAD), however, its prevalence in the middle-age patients after coronary artery bypass grafting (CABG) has not been investigated. Purpose To assess the frequency of the LPA gene c.5673A&amp;gt;G variant (p.Ile4399Met; rs3798220) in Polish patients with CAD following CABG under 65 years of age and determined its association with laboratory and clinical variables. Materials and Methods We studied 215 patients with stable CAD, aged 59.5±4.9 years, who underwent primary and isolated CABG surgery (at age of 57.8±5.4 years), including 195 (90.8%) male. Clinical characteristics and analysis of the LPA c.5673A&amp;gt;G variant were performed. Results The genotype distribution was as follows: AA – 192 (89.3%), AG – 19 (8.8%), and GG – 4 (1.9%). The c.5673G allele carriers had higher Lp(a) level (106.5 [IQR 77.9-149.7] vs 10.4 [IQR 4.4-43.0] mg/dL, p&amp;lt;0.001) compared with non-carriers. Among the c.5673G allele carriers, Lp(a) correlated positively with pack-years of smoking (r=0.563, p=0.045) and fibrinogen (r=0.431, p=0.040), but not with low-density lipoprotein cholesterol (r=0.202, 0.368). There were no other genotype-associated differences with regard to demographic and clinical variable between carriers and non-carriers, including myocardial infarction (56.5% vs 47.9%, p=0.511), peripheral artery disease (21.7% vs 15.1%, p=0.377) and cerebrovascular events (13.0% vs 6.7%, p=0.389). Conclusions To our knowledge, this is the first report on the prevalence of LPA rs3798220 variant in patients with advanced CAD following CABG surgery under 65 years of age. We showed a relatively high (10.7%) percentage of c.5673G allele carriers who have ten times higher Lp(a) levels compared to the wild type, however, its impact on cardiovascular events requires further studies.

The high-dose statin treatment reduces neutrophil extracellular traps formation in patients with coronary artery disease

Abstract Background Neutrophil extracellular traps formation (NETosis) is currently considered as an important mediator in atherosclerosis and atherothrombosis. However, the impact of high-dose statin treatment, as potent cholesterol-lowering agents with pleiotropic effects, on NETosis in coronary artery disease (CAD) has been poorly described. Purpose We sought to assess whether in CAD patients the recommended statin treatment intensification is associated with changes in NETs-related markers and if such changes can alter fibrin clot properties. Methods 130 patients with advanced CAD, who did not achieve the target low-density lipoprotein cholesterol (LDL-C) were included. Before and at least 6 months after initiation of high-dose statin therapy (rosuvastatin 40 mg/d or atorvastatin 80 mg/d) citrullinated histone H3 (H3cit), myeloperoxidase (MPO) and neutrophil elastase (NE) as markers associated with NETosis were assessed in relation to C-reactive protein (CRP), thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis proteins. Results At baseline, NETosis did not differ depending on gender and cardiovascular risk factors but H3cit correlated with MPO (R=0.543, P&amp;lt;0.001) and CRP (R=0.540, P&amp;lt;0.001). All NETosis markers were inversely correlated with Ks. Median LDL-C reduction by 25% (P&amp;lt;0.001) on high-dose statin treatment was independent from H3cit reduction by 30.4%, MPO by 28.1%, and NE by 25.5% (in all P&amp;lt;0.001, Figure 1). The ΔH3cit and ΔMPO, but not ΔNE were associated with ΔCRP (R=0.855, P&amp;lt;0.001; R=0.250, P=0.004, respectively), Δthrombin activatable fibrinolysis inhibitor (TAFI) (R=0.385, P&amp;lt;0.001; R=0.245, P=0.005), and inversely with ΔKs (R=-0.315, P&amp;lt;0.001; R=-0.395, P=0.001). In multivariable analysis the H3cit decrease was independently associated with ΔCRP (β=0.771, P&amp;lt;0.001), ΔTAFI (β=0.125, P=0.013) and Δfibrinogen (β=0.106, P=0.034) but not with ΔLDL-C. Conclusions As has been shown for the first time high-dose statin treatment reduces levels of NETs-related markers, regardless of lipid-lowering effect in CAD patients.

Cellular Characteristics and Protein Signatures of Human Adipose Tissues from Donors With or Without Advanced Coronary Artery Disease

Background/Objectives: Perivascular adipose tissue (PVAT) exerts a paracrine effect on blood vessels and our objective was to understand PVAT molecular signatures related to cardiovascular disease. Methods: We studied two groups: those undergoing mitral valve repair/replacement (VR, n = 16) and coronary artery bypass graft (CABG, n = 38). VR donors did not have coronary artery disease, whereas CABG donors had advanced coronary artery disease. Clinical and tissue pathologies and proteomics from adipose tissue were assessed. Results: Donors undergoing VR had a lower body mass index (p = 0.01), HbA1C (p = 0.0023), and incidence of diabetes (p = 0.022) compared to CABG. VR donors were overall healthier, with higher cardiac function compared to CABG donors, based on ejection fraction. Although adipose histopathology between groups was not markedly different, PVAT had smaller and more adipocytes compared to subcutaneous adipose tissues. These differences were validated by whole specimen automated morphological analysis, and anisotropy analysis showed small (2.8–7.5 μm) and large (22.8–64.4 μm) scale differences between perivascular and subcutaneous adipose tissue from CABG donors, and small scale changes (2.8–7.5 μm) between perivascular and subcutaneous adipose tissue from VR donors. Distinct protein signatures in PVAT and subcutaneous adipose tissue include those involved in secretion, exosomes and vesicles, insulin resistance, and adipocyte identity. Comparing PVAT and subcutaneous adipose tissue from CABG donors, there were 82 significantly different proteins identified with log fold change ≥ 0.3 or ≤−0.3 (p &lt; 0.05). Using this threshold, there were 36 differences when comparing PVAT and subcutaneous adipose tissue from VR donors, 58 differences when comparing PVAT from CABG or VR donors, and 55 when comparing subcutaneous adipose tissue from CABG vs. VR donors. Conclusions: Routine histopathology cannot differentiate between PVAT from donors with or without coronary artery disease, but multiscale anisotropy analysis discriminated between these populations. Our mass spectrometry analysis identified a cohort of proteins that distinguish between adipose depots, and are also associated with the presence or absence of coronary artery disease.

Analysis of Angiographic Patterns in Acute Coronary Syndrome Patients With Diabetes Mellitus: Correlation With HbA1c Levels.

Background The relation of diabetes mellitus with cardiovascular diseases is well-known, even acute coronary syndrome (ACS). High levels of glycated haemoglobin (HbA1c) are used is a sign oflong-term glycemic control and may be associated with severity in coronary artery disease (CAD). In this particular setting, the aim of this investigation was to examine the relationship between the HbA1c values and the angiographic patterns of patients who were admitted with an ACS diagnosis. Methodology A cross-sectional study included 120 patients diagnosed with ACS. The criteria for eligibility included patients with ST-elevation myocardial infarction, unstable angina, and non-ST elevation myocardial infarction with history of documented diabetes mellitus. Every patient had a suitable clinical examination, had their HbA1c checked, and had coronary angiography to determine the severity of their CAD. Descriptive statistics and ANOVA were performed for statistical analyses to determine the connection between angiographic patterns and HbA1c. Results Patients with elevated HbA1c levels demonstrated a strong association with severe coronary artery disease. Notably, those with HbA1c exceeding 10.5% exhibited significant triple vessel disease and Type C lesions, indicative of advanced coronary artery disease. Statistical analyses revealed a marked difference in angiographic patterns across various HbA1c categories (p < 0.05). Conclusion The findings of this study suggest that maintaining optimal HbA1c levels is essential for mitigating the severity of coronary artery disease in patients with ACS. Moreover, effective glycemic control may be protective against advanced coronary atherosclerosis and subsequent cardiovascular complications in both diabetic and non-diabetic individuals.

Intravascular ICG-enhanced NIRF-IVUS imaging to assess progressive atherosclerotic lesions in excised human coronary arteries

Indocyanine green (ICG)-enhanced intravascular near-infrared fluorescence (NIRF) imaging enhances the information obtained with intravascular ultrasound (IVUS) by visualizing pathobiological characteristics of atherosclerotic plaques. To advance our understanding of this hybrid method, we aimed to assess the potential of NIRF-IVUS to identify different stages of atheroma progression by characterizing ICG uptake in human pathological specimens. After excision, 15 human coronary specimens from 13 adult patients were ICG-perfused and imaged with NIRF-IVUS. All specimens were then histopathologically and immunohistochemically assessed. NIRF-IVUS imaging revealed colocalization of ICG-deposition to plaque areas of lipid accumulation, endothelial disruption, neovascularization and inflammation. Moreover, ICG concentrations were significantly higher in advanced coronary artery disease stages (p < 0.05) and correlated significantly to plaque macrophage burden (r = 0.67). Current intravascular methods fail to detect plaque biology. Thus, we demonstrate how human coronary atheroma stage can be assessed based on pathobiological characteristics uniquely captured by ICG-enhanced intravascular NIRF.

A Single-Surgeon Experience Transitioning to Total Arterial Revascularization.

Background: Coronary artery bypass grafting remains the standard of care for advanced and multifocal coronary artery disease; however, for patients that are surgical candidates, total arterial revascularization (TAR) remains underutilized due to concerns such as sternal wound infections and the learning curve. We present the results of a large cohort of mid-career surgeons transitioning to TAR, focusing on short-term outcomes and the learning curve. Methods: The surgeons transitioned to using TAR as the preferred revascularization technique in August of 2017. The Society of Thoracic Surgeons database was reviewed to identify all patients who underwent isolated non-emergent CABG performed by a single surgeon from January 2014 through January 2022. Patients were divided into two groups-those who had TAR and those who had traditional CABG using one internal mammary artery and vein grafts (IMA-SVG). Results: Eight hundred ninety-eight patients meet inclusion criteria (458 IMA-SVG and 440 TAR). The TAR group had slightly longer cardiopulmonary bypass time, cross clamp times, and operative times (all p < 0.05); however, ICU stay was shorter and 30-day readmission rate was lower for TAR compared to IMA-SVG (all p < 0.05). The TAR group also required fewer postoperative transfusions (p = 0.005). There was no difference in prolonged intubation, stroke, length of stay, mortality, or sternal wound complications between groups (all p > 0.05). The average TAR was 30 min longer; however, learning curves, stratified by number of grafts placed, showed no significant learning curve associated with TAR. Conclusions: An experienced surgeon transitioning from IMA-SVG to TAR slightly increases operative time, but decreases ICU stay, readmissions, and postoperative transfusions with no significant difference in rates of immediate post-operative complications or 30-day mortality, with a minimal learning curve.

Atrial Fibrillation Occurring After Smoking Marijuana: A Case Report and Review of the Literature.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, occurring primarily in individuals with known risk factors such as advanced age, heart failure, and coronary artery disease. Cannabis use produces several cardiovascular changes resulting in proarrhythmic effects on the heart. A 38-year-old woman with no significant past medical history presented to the emergency department (ED) complaining of palpitations with associated shortness of breath occurring after smoking marijuana. She was found to be in AF. Evaluation in the ED and during hospitalization found no cardiac or metabolic conditions that predisposed to AF. The AF resolved within three hours of onset without intervention. Cannabis use should be considered as a possible etiology of new-onset AF, especially in relatively young patients with no other predisposing risk factors.

Biochemical Signals of Survival: A Study on Mortality Markers in Coronary Bypass Surgery Patients.

Coronary bypass surgery remains a cornerstone treatment for advanced coronary artery disease. Identifying reliable predictors of postoperative mortality can significantly enhance patient care and outcomes. This study investigates the prognostic value of preoperative and postoperative amylase levels, creatinine, alanine aminotransferase, and aspartate aminotransferase as mortality markers in coronary bypass surgery patients. We conducted a retrospective analysis of 343 patients who underwent coronary bypass surgery. We compared the preoperative and postoperative biochemical markers (amylase, creatinine, alanine aminotransferase, and aspartate aminotransferase) of patients who died within the first week post-surgery (n = 52) and those who survived (n = 291). Statistical analyses included chi-square tests for categorical variables, t-tests for continuous variables, and receiver operating characteristic analysis for predicting mortality. No significant difference was observed in the distribution of blood groups between deceased and surviving patients. However, significant differences were noted in gender distribution and mean ages, with higher mortality observed in older and male patients. Preoperative creatinine levels were significantly higher in patients who died compared to survivors. Postoperatively, deceased patients exhibited significantly higher levels of amylase, creatinine, alanine aminotransferase, and aspartate aminotransferase. Receiver operating characteristic analysis revealed that postoperative amylase, creatinine, alanine aminotransferase, and aspartate aminotransferase values were good predictors of mortality, with amylase being the most significant predictor. This study highlights the importance of biochemical markers, particularly amylase, as predictors of mortality in patients undergoing coronary bypass surgery. The findings suggest that monitoring and managing amylase, creatinine, alanine aminotransferase, and aspartate aminotransferase levels pre- and post-surgery could improve patient outcomes. This study lays the groundwork for further research into the mechanistic links between these biochemical markers and patient survival, potentially leading to improved prognostic tools and therapeutic strategies.

Perioperative transfusion study (PETS): Does a liberal transfusion protocol improve outcome in high-risk cardiovascular patients undergoing non-cardiac surgery? A randomised controlled pilot study.

Small studies have shown that patients with advanced coronary artery disease might benefit from a more liberal blood transfusion strategy. The goal of this pilot study was to test the feasibility of a blood transfusion intervention in a group of vascular surgery patients who have elevated cardiac troponins in rest. We conducted a single-centre, randomised controlled pilot study. Patients with a preoperative elevated high-sensitive troponin T undergoing non-cardiac vascular surgery were randomised between a liberal transfusion regime (haemoglobin >10.4 g/dL) and a restrictive transfusion regime (haemoglobin 8.0-9.6 g/dL) during the first 3 days after surgery. The primary outcome was defined as a composite endpoint of all-cause mortality, myocardial infarction or unscheduled coronary revascularization. In total 499 patients were screened; 92 were included and 50 patients were randomised. Postoperative haemoglobin was different between the intervention and control group; 10.6 versus 9.8, 10.4 versus 9.4, 10.9 versus 9.4 g/dL on day one, two and three respectively (p < 0.05). The primary outcome occurred in four patients (16%) in the liberal transfusion group and in two patients (8%) in control group. This pilot study shows that the studied transfusion protocol was able to create a clinically significant difference in perioperative haemoglobin levels. Randomisation was possible in 10% of the screened patients. A large definitive trial should be possible to provide evidence whether a liberal transfusion strategy could decrease the incidence of postoperative myocardial infarction in high risk surgical patients.

Intramyocardial injection of hypoxia-conditioned extracellular vesicles increases myocardial perfusion in a swine model of chronic coronary disease

ObjectiveCoronary artery disease remains a leading cause of morbidity and mortality worldwide. Patients with advanced coronary artery disease who are not eligible for endovascular or surgical revascularization have limited options. Extracellular vesicles have shown potential to improve myocardial function in preclinical models. Extracellular vesicles can be conditioned to modify their components. Hypoxia-conditioned extracellular vesicles have demonstrated the ability to reduce infarct size and apoptosis in small animals. Our objective is to assess the potential benefits of hypoxia-conditioned extracellular vesicles in a large animal model of coronary artery disease. MethodsCoronary artery disease was induced in 14 Yorkshire swine by ameroid constriction of the left circumflex coronary artery. Two weeks postsurgery, swine underwent a repeat left thoracotomy for injections of hypoxia-conditioned extracellular vesicles (n = 7) or saline (control, n = 7). Five weeks later, all animals underwent terminal harvest for perfusion measurements and myocardial sectioning. ResultsMyocardial perfusion analysis demonstrated a trend toward increase at rest and a significant increase during rapid pacing (P = .09, P < .001). There were significant increases in activated phosphorylated endothelial nitric oxide synthase, endothelial nitric oxide synthase, phosphatidylinositol 3-kinase, phosphorylated protein kinase B, and the phosphorylated protein kinase B/protein kinase B ratio in the hypoxia-conditioned extracellular vesicles group compared with the control group (all P < .05). Additionally, there was a significant decrease in the antiangiogenic proteins collagen 18 and angiostatin (P = .01, P = .01) in the hypoxia-conditioned extracellular vesicles group. ConclusionsIntramyocardial injection of hypoxia-conditioned extracellular vesicles results in increased myocardial perfusion without a corresponding change in vessel density. Therefore, this improvement in perfusion is possibly due to changes in nitric oxide signaling. Hypoxia-conditioned extracellular vesicles represent a potential therapeutic strategy to increase myocardial perfusion in patients with advanced coronary artery disease.

Clinical impact of sarcopenia on long-term mortality in patients undergoing coronary bypass grafting

Abstract Funding Acknowledgements None. Aims Sarcopenia is an aging-related condition characterized by loss of skeletal muscle mass and is an indicator of subclinical atherosclerosis. The relationship between sarcopenia and long-term clinical outcomes in patients with advanced coronary artery disease who have undergone coronary artery bypass grafting (CABG) is not fully understood. We evaluated the prognostic implications of sarcopenia in patients undergoing CABG. Methods and Results A total of 2,810 patients who underwent CABG was analyzed and classified according to presence of sarcopenia. The skeletal muscle index (SMI) was calculated as L3 muscle area (cm2)/height (m)2 on computed tomography. Sarcopenia was defined as SMI ≤45 cm2/m2 in men and ≤38 cm2/m2 in women. The primary outcome was all-cause mortality during follow-up. The median follow-up was 8.7 years, and 924 patients (32.9%) had sarcopenia. Patients with sarcopenia were older and more frequently women. SMI was significantly correlated with age (R=-0.34, P&amp;lt;0.001), weight (R=-0.56, P&amp;lt;0.001), and body mass index (R=-0.52, P&amp;lt;0.001). SMI was significantly associated with risk of death on a restricted cubic spline curve (HR=1.04 per-1 decrease, 95% CI 1.03-1.05, P&amp;lt;0.001). Patients with sarcopenia had a higher incidence of long-term mortality than those without sarcopenia (survival rate 41.4% vs. 62.8%; adjusted HR=1.18, 95% CI 1.03-1.36, P=0.02). Subgroup analysis showed that the prognostic implication of sarcopenia on long-term survival was more evident in men (adjusted HR=2.01, 95% CI 1.72-2.35) than women (adjusted HR=1.28, 95% CI 0.98-1.68) (interaction P=0.006). Conclusions Sarcopenia, defined by SMI on computed tomography, was associated with long-term mortality after CABG.