Aetiology and predictors of major bleeding events in patients with heart failure with reduced ejection fraction undergoing percutaneous coronary intervention.

OBJECTIVES: We sought to determine the relationship between the degree of left ventricular ejection fraction (LVEF) impairment and the frequency and type of bleeding events after percutaneous coronary intervention (PCI). DESIGN: This was an observational retrospective cohort analysis. Patients who underwent PCI from 2009 to 2017 were identified from our institutional National Cardiovascular Disease Registry (NCDR) CathPCI database. Patients were stratified by pre-PCI LVEF: preserved (≥50%), mildly reduced (41%-49%) and reduced (≤40%) LVEF. PRIMARY OUTCOME MEASURES: The outcome was major bleeding, defined by NCDR criteria. Events were classified based on bleeding aetiology and analysed by multivariable logistic regression. RESULTS: Among 13 537 PCIs, there were 817 bleeding events (6%). The rate of bleeding due to any cause, blood transfusion, gastrointestinal bleeding and coronary artery perforation or tamponade each increased in a stepwise fashion comparing preserved, mildly reduced and reduced LVEF reduction (p<0.05 for all comparisons). However, there were no differences in bleeding due to asymptomatic drops in haemoglobin, access site haematoma or retroperitoneal bleeding. After multivariable adjustment, mildly reduced and reduced LVEF remained independent predictors of bleeding events (OR 1.36, 95% CI 1.06 to 1.74, p<0.05 and OR 1.73, 95% CI 1.45 to 2.06, p<0.0001). CONCLUSIONS: The degree of LV dysfunction is an independent predictor of post-PCI major bleeding events. Patients with mildly reduced or reduced LVEF are at greatest risk of post-PCI bleeding, driven by an increased need for blood transfusion, major GI bleeding events and coronary artery perforation or tamponade. Pre-PCI LV dysfunction does not predict asymptomatic declines in haemoglobin, access site haematoma or retroperitoneal bleeding.

Development and implementation of a treatment pathway to reduce coronary angiograms - lessons from a failure.

BACKGROUND: The rates of coronary angiograms (CA) and related procedures (percutaneous intervention [PCI]) are significantly higher in Germany than in other Organisation for Economic Co-ordination and Development (OECD) countries. The current guidelines recommend non-invasive diagnosis of coronary heart disease (CHD); CA should only have a limited role in choosing the appropriate revascularisation procedure. The aim of the present study was to explore whether improvements in guideline adherence can be achieved through the implementation of regional treatment pathways. We chose four regions of Germany with high utilisation of CAs for the study. Here we report the results of the concomitant qualitative study. METHODS: General practitioners and specialist physicians (cardiologists, hospital-based cardiologists, emergency physicians, radiologists and nuclear medicine specialists) caring for patients with suspected CHD were invited to develop regional treatment pathways. Four academic departments provided support for moderation, provision of materials, etc. The study team observed session discussions and took notes. After the development of the treatment pathways, 45 semi-structured interviews were conducted with the participating physicians. Interviews and field notes were transcribed verbatim and underwent qualitative content analysis. RESULTS: Pathway development received little support among the participants. Although consensus documents were produced, the results were unlikely to improve practice. The participants expressed very little commitment to change. Although this attempt clearly failed in all study regions, our experience provides relevant insights into the process of evidence appraisal and implementation. A lack of organisational skills, ignorance of current evidence and guidelines, and a lack of feedback regarding one's own clinical behaviour proved to be insurmountable. CA was still seen as the diagnostic gold standard by most interviewees. CONCLUSIONS: Oversupply and overutilisation can be assumed to be present in study regions but are not immediately perceived by clinicians. The problem is unlikely to be solved by regional collaborative initiatives; optimised resource planning within the health care system combined with appropriate economic incentives might best address these issues.

Footsteps to Wellness: A Systematic Review and Meta-Analysis of Walking Pace and Coronary Artery Disease Event.

Coronary artery disease (CAD) poses a global health challenge, necessitating effective preventive strategies. Despite the pivotal role of physical activity in cardiovascular health, many fall short of recommended guidelines for daily physical activity. Simple and accessible, walking presents an opportunity, with increased pace emerging as a potential strategy for reducing the risk of cardiovascular diseases. Thus, we aimed to elucidate the potential association between walking pace and the risk of CAD events in adults without a prior history of CAD through a systematic review. We searched PubMed, Scopus, Web of Science, and ScienceDirect without publication date restrictions to identify prospective cohorts that analyzed walking pace and adult CAD events. The literature search conducted from April 02, 2023, to August 21, 2023, identified a total of four studies (six cohorts) for meta-analysis using random-effects models. The Newcastle-Ottawa Scale was used to assess study quality, and data extraction involved two independent reviewers. The analysis calculated overall relative risks (RRs) and 95% confidence intervals (CIs) for those with the quickest walking paces compared to those with the slowest walking paces. A funnel plot analysis for publication bias and subgroup analysis were also conducted. Results from the meta-analysis involving 160,519 participants and 3,351 CAD events demonstrated a 46% decreased risk for those walking at the quickest pace (pooled RR = 0.54, 95% CI = 0.45-0.66). No significant heterogeneity was observed. In conclusion, walking pace emerges as a significant risk factor for CAD events in adults without a prior history of CAD. It serves as a potential screening tool to identify individuals at higher risk. Promoting a faster walking pace as a daily activity may effectively mitigate the burden of CAD.

Impacts of pro-inflammatory cytokines variant on cardiometabolic profile and premature coronary artery disease: A systematic review and meta-analysis.

Interleukin-6 (IL-6), a pivotal pro-inflammatory cytokine, is closely linked to vascular wall thickening and atherosclerotic lesion. Since serum IL-6 levels are largely determined by the genetic variant in IL-6, this study was conducted to investigate whether the IL-6 variant impacts cardiometabolic profile and the risk of premature coronary artery disease (PCAD). PubMed, Cochrane Library, Central, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ClinicalTrials.gov were searched from May 13, 2022 to June 28, 2023. In total, 40 studies (26,543 individuals) were included for the analysis. The rs1800795 (a function variant in the IL-6 gene) C allele was linked to higher levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), fasting plasma glucose (FPG), body mass index (BMI), and waist circumference (WC), and a lower levels of high-density lipoprotein cholesterol (HDL-C). However, no significant association was observed of rs1800795 with triglycerides (TG), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Interestingly, a significant association was detected between rs1800795 and PCAD. Subgroup analyses indicted that the impacts of rs1800795 on cardiometabolic risk factors were significant in Caucasians but stronger in obese patients. In contrast, the impact of rs1800795 on PCAD was significant in brown race population. In summary, rs1800795 had a slight but significant impact on cardiometabolic risk factors and PCAD. IL-6 inhibition with ziltivekimab or canakinumab may benefit high-risk populations (e.g. brown race population, Caucasians, obese patients, etc.) with rs1800795 to prevent PCAD.

Cardiovascular morbidity and mortality following hypertensive disorders of pregnancy.

OBJECTIVES: To determine whether hypertensive disorders of pregnancy (HDP) are associated with maternal coronary artery disease (CAD) and other cardiovascular (CV) diseases within 10-20 years following delivery. STUDY DESIGN: Retrospective cohort including all women who delivered ≥ 1 pregnancy ≥ 20 weeks' gestation within a single health system from 1998 to 2008. We excluded those with CV risk factors preceding first delivery or with no follow-up after delivery. The exposure of interest was any HDP, determined by ICD coding. MAIN OUTCOME MEASURES: The primary outcome was a composite of ICD codes for CAD, peripheral vascular disease, and CV events (myocardial infarction, stroke, and death). Multivariable Cox proportional hazards estimated the association between exposure and outcomes. A nested cohort of women who underwent cardiac catheterization had a primary outcome of angiographic CAD, and multivariable logistic regression estimated the association between HDP and CAD. RESULTS: Of 33,959 women included, 2,385 women had HDP. HDP was associated with the composite outcome (adjusted HR 1.50, 95 % CI 1.11, 2.03). There was a significant difference in event-free survival between groups (p = 0.003) with a median follow-up of 17.3 years. 592 women (1.7 %) underwent cardiac catheterization: 20 of 90 women with HDP had CAD (22.2 %) on angiography vs 49 of 502 without HDP (9.8 %, p < 0.001). HDP was associated with angiographic CAD (adjusted OR 2.08, 95 % CI 1.05, 4.11). CONCLUSIONS: Women with HDP had twice the incidence of CAD on angiography compared to parous women without HDP. Obstetric history may inform the decision to perform cardiac catheterization in relatively young women.

Unstable Angina Risk Stratification Using High-Sensitivity Cardiac Troponin and Coronary Angiography.

Patients formerly diagnosed with unstable angina (UA) are being reclassified as non-ST-elevation myocardial infarction with the widespread adoption of high-sensitivity troponin (hsTn) assays, leading to significant changes in the incidence and prognosis of UA. This study aimed to evaluate the value of hsTn and the presence of significant obstructive coronary artery disease (CAD) in the risk stratification of patients with UA. We conducted a retrospective, single-center study of 742 patients hospitalized for UA between 2016 and 2021. The primary end point of this study was all-cause mortality. The secondary outcome (major adverse cardiac events [MACEs]) was defined as a composite of nonfatal myocardial infarction (MI), hospitalization for heart failure (hHF), and repeated coronary angiography because of recurring UA (rUA) after the index event. The outcomes were assessed within 1 month, 1 year, and up to 5 years of follow-up. The average follow-up duration was 45 ± 24 months, and 37.2% (n = 276) of patients completed a 5-year follow-up. No in-hospital death was observed, and 6.9% of patients died during follow-up, which was more commonly a late event (>12 months). The composite secondary end point (MI+hHF+rUA) was observed in 16.7% of the patients. There were 3.2% nonfatal MI, 2.3% hHF, and 11.6% rUA during follow-up. We developed a risk model (UA mortality risk) using variables with the highest discriminatory power: age, hsTn, and ST-segment deviation. Our model performed well against the Global Registry of Acute Coronary Events and Thrombolysis in Myocardial Infarction risk scores in predicting death during follow-up. Obstructive CAD on coronary angiography was the only independent predictor of MACEs during follow-up. In conclusion, a contemporary cohort of patients with UA presented with favorable prognosis, particularly, within the first year after the index event. Nonsignificant increases in hsTn levels add to the risk stratification of patients with UA, and the presence of obstructive CAD was the only independent predictor of MACEs, highlighting the potential importance of assessing coronary anatomy.

GlycA Levels Independently Predict Coronary Artery Calcium Incidence and Progression in the ELSA-Brasil Cohort (Brazilian Longitudinal Study of Adult Health).

Atherosclerosis is an inflammatory disease. Coronary artery calcium (CAC) is a marker of atherosclerotic disease events and mortality risk. Increased GlycA, an emerging marker of inflammation, is associated with a higher risk for coronary artery disease (CAD). However, there is conflicting evidence on whether GlycA predicts subclinical CAD progression. We hypothesized that GlycA can predict subclinical CAC incidence/progression in healthy participants. We included 2,690 ELSA-Brasil cohort participants without cardiovascular/chronic inflammatory disease not receiving statin therapy who had GlycA levels measured and 2 interval CAC assessments between 2010 and 2018. Multivariable logistic and linear regression models were computed to evaluate GlycA as a predictor of CAC incidence and progression. CAC incidence required a baseline CAC of 0. CAC progression required a baseline CAC >0. The mean age of participants was 48.6 ± 7.7 years, 56.7% were women, and 54.6% and 16.1% (429 of 2,690) were White and Black, respectively. The mean CAC interscan period was 5.1 ± 0.9 years, the mean GlycA level was 414.7 ± 65 µmol/L, and the incidence of CAC was 13.1% (280 of 2,129). The GlycA level odds ratio for CAC incidence was 1.002 (95% confidence interval 1.0005 to 1.005, p = 0.016), adjusted for demographics, lifestyle, a family history of early CAD (≤60 years), lipids, and co-morbidities. The GlycA (≤p25 vs ≥p75) odds ratio for CAC progression (Berry definition) was 1.77 (95% confidence interval 1.07 to 2.96, p = 0.03) in a similar multivariable-adjusted model. Higher GlycA levels were associated with CAC incidence and progression in a healthy Brazilian cohort.

The additive effect of metabolic syndrome on left ventricular impairment in patients with obstructive coronary artery disease assessed by 3.0 T cardiac magnetic resonance feature tracking.

BACKGROUND: Metabolic syndrome (MetS) can increase the risk of morbidity and mortality of cardiovascular disease and obstructive coronary artery disease (OCAD), which usually have a poor prognosis. This study aimed to explore the impact of MetS on left ventricular (LV) deformation and function in OCAD patients and investigate the independent factors of impaired LV function and deformation. MATERIALS AND METHODS: A total of 121 patients with OCAD and 52 sex- and age-matched controls who underwent cardiac magnetic resonance scanning were enrolled in the study. All OCAD patients were divided into two groups: OCAD with MetS [OCAD(MetS+), n = 83] and OCAD without MetS [OCAD(MetS-), n = 38]. LV functional and global strain parameters were measured and compared among the three groups. Multivariable linear regression analyses were constructed to investigate the independent factors of LV impairment in OCAD patients. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to test the prediction efficiency of MetS for LV impairment. RESULTS: From controls to the OCAD(MetS-) group to the OCAD(MetS+) group, LV mass (LVM) increased, and LV global function index (LVGFI) and LV global longitudinal peak strain (GLPS) decreased (all p < 0.05). Compared with the OCAD(MetS-) group, the LV GLPS declined significantly (p = 0.027), the LVM increased (p = 0.006), and the LVGFI decreased (p = 0.043) in the OCAD(MetS+) group. After adjustment for covariates in OCAD patients, MetS was an independent factor of decreased LV GLPS (ß = - 0.211, p = 0.002) and increased LVM (ß = 0.221, p = 0.003). The logistic multivariable regression analysis and ROC analysis showed that combined MetS improved the efficiency of predicting LV GLPS reduction (AUC = 0.88) and LVM (AUC = 0.89) increase. CONCLUSIONS: MetS aggravated the damage of LV deformation and function in OCAD patients and was independently associated with LV deformation and impaired LV strain. Additionally, MetS increased the prediction efficiency of increased LVM and decreased LV GLPS. Early detection and intervention of MetS in patients with OCAD is of great significance.

The relationship between complement C1q and coronary plaque vulnerability based on optical coherence tomography analysis.

To determine the association between complement C1q and vulnerable plaque morphology among coronary artery disease (CAD) patients. We conducted a retrospective observational study of 221 CAD patients admitted to The Second Affiliated Hospital of Xi'an Jiaotong University. Intravascular optical coherence tomography was utilized to describe the culprit plaques' morphology. Using logistic regression analysis to explore the correlation between C1q and vulnerable plaques, and receiver operator characteristic (ROC) analysis assess the predictive accuracy. As reported, the complement C1q level was lower in ACS patients than CCS patients (18.25 ± 3.88 vs. 19.18 ± 4.25, P = 0.045). The low complement-C1q-level group was more prone to develop vulnerable plaques. In lipid-rich plaques, the complement C1q level was positively correlated with the thickness of fibrous cap (r = 0.480, P = 0.041). Univariate and multivariate logistic regression analyses suggested that complement C1q could be an independent contributor to plaques' vulnerability. For plaque rupture, erosion, thrombus, and cholesterol crystals, the areas under the ROC curve of complement C1q level were 0.873, 0.816, 0.785, and 0.837, respectively (P < 0.05 for all). In CAD patients, the complement C1q could be a valuable indicator of plaque vulnerability.

Congenital Absence of Pericardium: A Case Report and Technical Considerations in Cardiac Surgery.

This case report describes a rare instance of left-sided congenital pericardial agenesis (CPA) encountered during coronary artery bypass grafting (CABG) in a 77-year-old male. In this unique case, the presence of an unusual strip of left pericardium containing the phrenic nerve posed significant surgical challenges. Special attention was required for the graft lay, ensuring adequate filling of the heart during assessment before closure, as well as emphasis on the need for generous graft length. Additionally, the evaluation of graft positioning prior to cardiopulmonary bypass was crucial. Despite these complexities, CABG was successfully performed with no complications to note. This case underscores the importance of adaptability in surgical technique to manage the unique challenges posed by CPA, leading to a positive outcome despite the atypical cardiac anatomy.

Going beyond summed stress scores: Correlating global and territorial coronary flow reserve by single photon emission tomography with routine myocardial perfusion imaging.

a Background: Technological advancement in the recent years has enabled the application of single photon emission tomography (SPECT) to evaluate myocardial blood flow (MBF). This method offers increased sensitivity in the assessment of coronary health, quantifiable through non-invasive imaging beyond the more conventional methods such as with myocardial perfusion imaging (MPI). b Aims: To correlate MBF, derived by dynamic SPECT, both global and by coronary territories to the summed stress scores (SSS) on conventional MPI. c Methods: Images obtained from dipyridamole-gated SPECT MPI stress and rest studies performed on recruited subjects were examined. We calculated the global and regional coronary flow reserve (CFR) via a standard software package, taken as the ratio of stress MBF to rest MBF, using CFR<2.5 as the cut off. d Results: Amongst the 90 recruited subjects (mean age 67 ± 8 years; of which 76% were males), 49% had MPI within normal limits (summed stress score (SSS) 0-3; Left ventricular ejection fraction (LVEF) > 50%). We observed a progressive reduction in global and regional CFR across the normal SSS category to that of severely abnormal (SSS >13). Reduced global CFR with correspondent lower CFR across the regional arteries were detected in scans within normal limits of MPI scans in subjects who were older (69 ± 7 vs. 62 ± 9 years, p = 0.034). Decreasing CFR was significantly associated with increasing age across the regional arteries. e Conclusion: In our study we depict the global and regional MBF values obtained via SPECT MPI in correlation to the respective SSS categories. Our data proposes that dynamic SPECT has a part in refining cardiac risk stratification, particularly in the older adult population, who are at greater risk.

Addressing comprehensive complexities a striking familial hypercholesterolemia case study.

BACKGROUND: Premature aortic involvement and comprehensive management strategies in familial hypercholesterolemia familial hypercholesterolemia (FH), a rare autosomal dominant genetic disorder, poses significant challenges due to its propensity for elevated low-density lipoprotein cholesterol, premature coronary heart disease, and vascular atherosclerosis. CASE PRESENTATION: Unraveling Cardiovascular Complexities: A Striking Familial Hypercholesterolemia. This case study delves into a remarkable instance of FH in a 16-year-old female who presented with chest pain and worsening dyspnea. Diagnostic evaluation revealed distinct electrocardiographic changes, elevated troponin levels, and profound dyslipidemia. Remarkable findings on transthoracic echocardiography, computed tomography angiography, and catheterization prompted multidisciplinary interventions and demonstrated remarkable enhancements in ventricular function, mitral regurgitation, and aortic stenosis. CONCLUSION: The case study underscores the urgency of comprehensive management strategies in confronting the myriad challenges of FH, emphasizing the value of early intervention, innovative therapies, and rigorous imaging modalities for unraveling the intricate cardiovascular manifestations of this condition.

The association between O2-pulse slope ratio and functional severity of coronary stenosis: A combined cardiopulmonary exercise testing and quantitative flow ratio study.

Background: The role of cardiopulmonary exercise testing (CPET) parameters in evaluating the functional severity of coronary disease remains unclear. The aim of this study was to quantify the O2-pulse morphology and investigate its relevance in predicting the functional severity of coronary stenosis, using Murray law-based quantitative flow ratio (µQFR) as the reference. Methods: CPET and µQFR were analyzed in 138 patients with stable coronary artery disease (CAD). The O2-pulse morphology was quantified through calculating the O2-pulse slope ratio. The presence of O2-pulse plateau was defined according to the best cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8. Results: The optimal cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8 was 0.4, with area under the curve (AUC) of 0.632 (95 % CI: 0.505-0.759, p = 0.032). The total discordance rate between O2-pulse slope ratio and µQFR was 27.5 %, with 13 patients (9.4 %) being classified as mismatch (O2-pulse slope ratio > 0.4 and µQFR ≤ 0.8) and 25 patients being classified as reverse-mismatch (O2-pulse slope ratio ≤ 0.4 and µQFR > 0.8). Angiography-derived microvascular resistance was independently associated with mismatch (OR 0.07; 95 % CI: 0.01-0.38, p = 0.002) and reverse-mismatch (OR 9.76; 95 % CI: 1.47-64.82, p = 0.018). Conclusion: Our findings demonstrate the potential of the CPET-derived O2-pulse slope ratio for assessing myocardial ischemia in stable CAD patients.

Exploring of gut microbiota features in dyslipidemia and chronic coronary syndrome patients undergoing coronary angiography.

Chronic coronary syndrome (CCS) has a high mortality rate, and dyslipidemia is a major risk factor. Atherosclerosis, a cause of CCS, is influenced by gut microbiota dysbiosis and its metabolites. The objective of this study was to study the diversity and composition of gut microbiota and related clinical parameters among CCS patients undergoing coronary angiography and dyslipidemia patients in comparison to healthy volunteers in Thailand. CCS patients had more risk factors and higher inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) than others. The alpha diversity was lower in dyslipidemia and CCS patients than in the healthy group. A significant difference in the composition of gut microbiota was observed among the three groups. The relative abundance of Proteobacteria, Fusobacteria, Enterobacteriaceae, Prevotella, and Streptococcus was significantly increased while Roseburia, Ruminococcus, and Faecalibacterium were lower in CCS patients. In CCS patients, Lachnospiraceae, Peptostreptococcaceae, and Pediococcus were positively correlated with hs-CRP. In dyslipidemia patients, Megasphaera was strongly positively correlated with triglyceride (TG) level and negatively correlated with high-density lipoprotein cholesterol (HDL-C). The modification of gut microbiota was associated with changes in clinical parameters involved in the development of coronary artery disease (CAD) in CCS patients.

Impact of Clinical and Sociodemographic Factors on Quality of Life Following Coronary Artery Bypass Grafting: A Mixed-Methods Study.

INTRODUCTION: Coronary artery bypass grafting (CABG) is an essential surgical management modality for patients with coronary artery disease. Health-related quality of life (HRQoL) has become important because of the significant decrease in the mortality rate associated with CABG. We aimed to explore the factors that affect the quality of life after CABG. METHODS: This study used a descriptive correlational design to assess the determinants of HRQoL using the 36-item Short Form Health Survey questionnaire (SF-36). Patients who underwent CABG at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, between March 2015 and December 2021 were enrolled in this study. Overall, 275 participants were eligible for our study, of which 84 were found to be valid for analysis. Phone contacts were made directly with the patient after briefly explaining the study. Scores and clinical data were investigated using multivariable linear regression analysis. RESULTS: Subscales of role limitations due to physical issues had the lowest mean scores, followed by vitality and general health (57.4 ± 44.7; 60.4 ± 25.6; 64.1 ± 22.6), respectively. However, social functioning (78.9 ± 29.0) and pain (75.1 ± 29.9) had the highest scores of all subscales. A history of congestive heart failure (CHF) was independently associated with lower scores for physical role limitations (p = 0.021), vitality (p = 0.001), general health (p< 0.001), and mental health (p = 0.011). Lower mental health scores were also predicted by being a widow (p = 0.030), whereas lower general health scores were predicted by being unemployed (p = 0.001) and having a peripheral vascular disease (PVD) (p = 0.043). Additionally, the development of postoperative complications was an independent predictor of lower physical functioning (p = 0.028) and vitality (p = 0.043). Regarding the number of grafts, cardiopulmonary bypass, and cross-clamp time, no significant impact was found on any of the SF-36 subscales (p> 0.05). CONCLUSION: The postoperative decline in HRQoL was attributed to comorbidities such as CHF and PVD, postoperative complications including bleeding and wound infection, as well as unemployment and widowed status. Therefore, choosing the appropriate patients for surgery and post-discharge follow-up may enhance HRQoL.

Concordance between vessel-specific and vascular territory coronary functional assessment: A comparison of quantitative flow ratio and myocardial perfusion scintigraphy.

BACKGROUND: Quantitative flow ratio (QFR) and myocardial perfusion scintigraphy (MPS) are utilized for assessing coronary artery disease (CAD) significance. We aimed to analyze their concordance and prognostic impact. AIMS: We aimed to analyze the concordance between QFR and MPS and their risk stratification. METHODS: Patients with invasive coronary angiography and MPS were categorized as concordant if QFR ≤ 0.80 and summed difference score (SDS) ≥ 4 or if QFR > 0.80 and SDS < 4; otherwise, they were discordant. Concordance was classified by coronary territory involvement: total (three territories), partial (two territories), poor (one territory), and total discordance (zero territories). Leaman score assessed coronary atherosclerotic burden. RESULTS: 2010 coronary territories (670 patients) underwent joint QFR and MPS analysis. MPS area under the curve for QFR ≤ 0.80 was 0.637. Concordance rates were total (52.5%), partial (29.1%), poor (15.8%), and total discordance (2.6%). Most concordance occurred in patients without significant CAD or with single-vessel disease (89.5%), particularly without MPS perfusion defects (91.5%). Leaman score (odds ratio [OR]: 0.839, 95% confidence interval [CI]: 0.805-0.875, p < 0.001) and MPS perfusion defect (summed stress score [SSS] ≥ 4) (OR: 0.355, 95% CI: 0.211-0.596, p < 0.001) were independent predictors for discordance. After 1400 days, no significant difference in death/myocardial infarction was observed based on MPS assessment, but Leaman score, functional Leaman score, and average QFR identified higher risk patients. CONCLUSIONS: MPS showed good overall accuracy in assessing QFR significance but substantial discordance existed. Predictors for discordance included higher atherosclerotic burden and MPS perfusion defects (SSS ≥ 4). Leaman score, QFR-based functional Leaman score, and average QFR provided better risk stratification for all-cause death and myocardial infarction than MPS.

Metabolic score for insulin resistance predicts major adverse cardiovascular event in premature coronary artery disease.

BACKGROUND: The Metabolic Score for Insulin Resistance (METS-IR) index serves as a simple surrogate marker for insulin resistance (IR) and is associated with the presence and severity of coronary artery disease (CAD). However, the prognostic significance of METS-IR in patients with premature CAD remains unclear. This study aims to investigate the prognostic value of METS-IR in premature CAD. METHODS: This retrospective study included 582 patients diagnosed with premature CAD between December 2012 and July 2019. The median follow-up duration was 63 months (interquartile range, 44-81 months). The primary endpoint was Major Adverse Cardiovascular Events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction (MI), repeat coronary artery revascularization, and non-fatal stroke. RESULTS: Patients with MACE had significantly higher METS-IR levels than those without MACE (44.88±8.11 vs. 41.68±6.87, p<0.001). Kaplan-Meier survival curves based on METS-IR tertiles demonstrated a statistically significant difference (log-rank test, p<0.001). In the fully adjusted model, the Hazard Ratio (95% CI) for MACE was 1.41 (1.16-1.72) per SD increase in METS-IR, and the P for trend based on METS-IR tertiles was 0.001 for MACE. Time-dependent Receiver Operator Characteristic (ROC) analysis of METS-IR yielded an Area Under the Curve (AUC) of 0.74 at 2 years, 0.69 at 4 years, and 0.63 at 6 years. CONCLUSIONS: METS-IR serves as a reliable prognostic predictor of MACE in patients with premature CAD. Therefore, METS-IR may be considered a novel, cost-effective, and dependable indicator for risk stratification and early intervention in premature CAD.

Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis.

BACKGROUND: While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological relevance of these changes remains poorly understood. METHODS: Single-cell RNA sequencing data generated with SmartSeq2 (≈8000 genes/cell) in nearly 19 000 single cells isolated during atherosclerosis progression in Ldlr-/-Apob100/100 mice with human-like plasma lipoproteins and from humans with asymptomatic and symptomatic carotid plaques was clustered into multiple subtypes. For clinical and pathophysiological context, the advanced-stage and symptomatic subtype clusters were integrated with 135 tissue-specific (atherosclerotic aortic wall, mammary artery, liver, skeletal muscle, and visceral and subcutaneous, fat) gene-regulatory networks (GRNs) inferred from 600 coronary artery disease patients in the STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) study. RESULTS: Advanced stages of atherosclerosis progression and symptomatic carotid plaques were largely characterized by 3 smooth muscle cells (SMCs), and 3 macrophage subtype clusters with extracellular matrix organization/osteogenic (SMC), and M1-type proinflammatory/Trem2-high lipid-associated (macrophage) phenotypes. Integrative analysis of these 6 clusters with STARNET revealed significant enrichments of 3 arterial wall GRNs: GRN33 (macrophage), GRN39 (SMC), and GRN122 (macrophage) with major contributions to coronary artery disease heritability and strong associations with clinical scores of coronary atherosclerosis severity (SYNTAX/Duke scores). The presence and pathophysiological relevance of GRN39 were verified in 5 independent RNAseq data sets obtained from the human coronary and aortic artery, and primary SMCs and by targeting its top-key drivers, FRZB and ALCAM, in cultured human vascular SMCs. CONCLUSIONS: By identifying and integrating the most gene-rich single-cell subclusters of atherosclerosis to date with a coronary artery disease framework of GRNs, GRN39 was identified and independently validated as being critical for the transformation of contractile SMCs into an osteogenic phenotype promoting advanced-stage, symptomatic atherosclerosis.

Clinical Significance of Coronary Arterial Dominance: A Review of the Literature.

Coronary dominance describes the anatomic variation of coronary arterial supply, notably as it relates to perfusion of the inferior cardiac territories. Differences in the development and outcome in select disease states between coronary dominance patterns are increasingly recognized. In particular, observational studies have identified higher prevalence of poor outcomes in left coronary dominance in the setting of ischemic, conduction, and valvular disease. In this qualitative literature review, we summarize anatomic, physiologic, and clinical implications of differences in coronary dominance to highlight current understanding and gaps in the literature that should warrant further studies.