Sex-specific presentation, care, and clinical events in individuals admitted with NSTEMI: the ACVC-EAPCI EORP NSTEMI registry of the European Society of Cardiology.

AIMS: Women have historically been disadvantaged in terms of care and outcomes for non-ST-segment elevation myocardial infarction (NSTEMI). We describe patterns of presentation, care, and outcomes for NSTEMI by sex in a contemporary and geographically diverse cohort. METHODS AND RESULTS: Prospective cohort study including 2947 patients (907 women, 2040 men) with Type I NSTEMI from 287 centres in 59 countries, stratified by sex. Quality of care was evaluated based on 12 guideline-recommended care interventions. The all-or-none scoring composite performance measure was used to define receipt of optimal care. Outcomes included acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack, BARC Type ≥3 bleeding, or death in-hospital, as well as 30-day mortality. Women admitted with NSTEMI were older, more comorbid, and more frequently categorized as at higher ischaemic (GRACE >140, 54.0% vs. 41.7%, P < 0.001) and bleeding (CRUSADE >40, 51.7% vs. 17.6%, P < 0.001) risk than men. Women less frequently received invasive coronary angiography (ICA; 83.0% vs. 89.5%, P < 0.001), smoking cessation advice (46.4% vs. 69.5%, P < 0.001), and P2Y12 inhibitor prescription at discharge (81.9% vs. 90.0%, P < 0.001). Non-receipt of ICA was more often due to frailty for women than men (16.7% vs. 7.8%, P = 0.010). At ICA, more women than men had non-obstructive coronary artery disease or angiographically normal arteries (15.8% vs. 6.3%, P < 0.001). Rates of in-hospital adverse outcomes and 30-day mortality were low and did not differ by sex. CONCLUSION: In contemporary practice, women presenting with NSTEMI, compared with men, less frequently receive antiplatelet prescription, smoking cessation advice, or are considered eligible for ICA.

Cohort profile: the ESC EURObservational Research Programme Non-ST-segment elevation myocardial infraction (NSTEMI) Registry.

AIMS: The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Non-ST-segment elevation myocardial infarction (NSTEMI) Registry aims to identify international patterns in NSTEMI management in clinical practice and outcomes against the 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without ST-segment-elevation. METHODS AND RESULTS: Consecutively hospitalised adult NSTEMI patients (n = 3620) were enrolled between 11 March 2019 and 6 March 2021, and individual patient data prospectively collected at 287 centres in 59 participating countries during a two-week enrolment period per centre. The registry collected data relating to baseline characteristics, major outcomes (in-hospital death, acute heart failure, cardiogenic shock, bleeding, stroke/transient ischaemic attack, and 30-day mortality) and guideline-recommended NSTEMI care interventions: electrocardiogram pre- or in-hospital, pre-hospitalization receipt of aspirin, echocardiography, coronary angiography, referral to cardiac rehabilitation, smoking cessation advice, dietary advice, and prescription on discharge of aspirin, P2Y12 inhibition, angiotensin converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB), beta-blocker, and statin. CONCLUSION: The EORP NSTEMI Registry is an international, prospective registry of care and outcomes of patients treated for NSTEMI, which will provide unique insights into the contemporary management of hospitalised NSTEMI patients, compliance with ESC 2015 NSTEMI Guidelines, and identify potential barriers to optimal management of this common clinical presentation associated with significant morbidity and mortality.

Three-Year Impact of Immediate Invasive Strategy in Patients With Non-ST-Segment Elevation Myocardial Infarction (from the RIDDLE-NSTEMI Study).

Previous studies compared clinical outcomes of early versus delayed invasive strategy in patients with non-ST-elevation acute coronary syndrome up to 1-year follow-up, but long-term data remain scarce. Our aim was to evaluate the long-term effects of immediate invasive intervention in patients with Non-ST-Segment Elevation Myocardial Infarction (NSTEMI). The Randomized Study of Immediate Versus Delayed Invasive Intervention in Patients With Non-ST-Segment Elevation Myocardial Infarction (RIDDLE-NSTEMI) was a randomized, investigator-initiated, parallel-group trial that assigned 323 patients with NSTEMI (1:1) to either immediate (median time to intervention 1.4 hours) or delayed invasive strategy (61.0 hours). The primary end point was the composite of death or new myocardial infarction (MI). At 3 years, immediate invasive intervention was associated with a lower rate of death or new MI, compared with a delayed invasive strategy (12.3% vs 22.5%, hazard ratio 0.50, 95% confidence interval 0.29 to 0.87, p = 0.014). The observed benefit of immediate intervention was mainly driven by an increased early reinfarction risk in delayed strategy, with similar new MI rates beyond 30 days (4.4% in the immediate and 5.6% in the delayed group, p = 0.61). Three-year mortality was 9.3% in the immediate invasive strategy, and 10.0% in the delayed strategy (p = 0.83). High baseline Global Registry of Acute Coronary Events score (>140) was associated with a significant increase in long-term mortality, regardless of the timing of invasive intervention. In conclusion, whereas immediate invasive intervention significantly reduced the early risk of new MI, the timing of invasive intervention appears to have no significant impact on clinical outcomes beyond 30 days, which seem to mostly be related to the baseline clinical risk profile.

The HACD4 haplotype as a risk factor for atherosclerosis in males.

The 9p21.3 region is rich in regulatory elements and the variants in this region had been robustly associated with carotid plaque (CP) and coronary artery disease (CAD). Recently, the HACD4 was detected as one of the six 9p21.3 differentially expressed genes associated with accelerated atherosclerosis and greater mean lesion area in the Athsq1 congenic mice. We aimed to investigate association of two potentially regulatory HACD4 variants (rs36212560 I/D, rs2275888 T/C) and their haplotypes with CP occurrence and the level of HACD4 and FOCAD mRNA in human CP tissue. Association study was replicated in CAD patients who suffered the first myocardial infarction. Study included 477 CP patients, 303 healthy controls and replication sample of 224 CAD males from the population of Serbia. Genotypes were determined by polymerase chain reaction (PCR) and real-time PCR using TaqMan® technology. The gene expression was detected with TaqMan® technology. We have found significant and independent association of DT haplotype with CP presence in men (adjusted OR=1.64 CI=1.12-2.42, p=0.011). The result was replicated in CAD males (adjusted OR=1.84 CI=1.21-2.80, p=0.004). We have found significant effect of the HACD4 rs2275888 on FOCAD mRNA level in human CP tissue. Correction for multiple testing was performed. Independent association of HACD4 haplotypes with atherosclerotic phenotypes connotes a further validation and replication in larger cohorts as well as functional studies to enlighten the potential mechanism of its action in pathophysiology of atherosclerosis.

Endothelial cell markers from clinician's perspective.

Endothelial cell markers are membrane-bound or cytoplasmic molecules expressed by endothelial cells, which help their easier identification and discrimination from other cell types. During vasculogenesis, endothelial cells differentiate from hemangioblasts to form new blood vessels. With the discovery of endothelial progenitor cells (EPC) and their ability to form new blood vessels, the term vasculogenesis is not only reserved for the embryonic development. Possibility of de novo blood vessel formation from EPC is now widely explored in different ischemic conditions, especially in cardiovascular medicine. Numerous clinical trials have tested enhancing tissue vascularization by delivering hematopoietic cells that expressed endothelial markers. This therapeutic approach proved to be challenging and promising, particularly for patients who have exhausted all conventional therapeutic modalities. Angiogenesis, which refers to the formation of new blood vessels from existing vasculature, is indispensable process during tumor progression and metastasis. Blockage of tumor angiogenesis by targeting and inhibiting endothelial cell has emerged as novel safe and efficacious method to control many advanced malignant diseases. Numerous clinical studies are currently testing new antiangiogenic drugs which target and inhibit endothelial cell markers, receptors or molecules which transmit receptor-mediated signals, therefore inhibiting endothelial cell proliferation, migration and vascular tube formation. Many of these drugs are now widely used in clinical settings as first- or second-line chemotherapy in advanced malignant conditions. So far, these therapeutic approaches gave modest, yet encouraging clinical improvements, prolonging survival and improving functional capacity and quality of life for many terminally ill patients. Here we present the most commonly used endothelial cell markers along with their applicability in contemporary clinical practice.

Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients: The RIDDLE-NSTEMI Study.

OBJECTIVES: This study aimed to assess the clinical impact of immediate versus delayed invasive intervention in patients with non-ST-segment myocardial infarction (NSTEMI). BACKGROUND: Previous studies found conflicting results on the effects of earlier invasive intervention in a heterogeneous population of acute coronary syndromes without ST-segment elevation. METHODS: We randomized 323 NSTEMI patients to an immediate-intervention group (<2 h after randomization, n = 162) and a delayed-intervention group (2 to 72 h, n = 161).The primary endpoint was the occurrence of death or new myocardial infarction (MI) at 30-day follow-up. RESULTS: Median time from randomization to angiography was 1.4 h and 61.0 h in the immediate-intervention group and the delayed-intervention group, respectively (p < 0.001). At 30 days, the primary endpoint was achieved less frequently in patients undergoing immediate intervention (4.3% vs. 13%, hazard ratio: 0.32, 95% confidence interval: 0.13 to 0.74; p = 0.008). At 1 year, this difference persisted (6.8% in the immediate-intervention group vs. 18.8% in delayed-intervention group; hazard ratio: 0.34, 95% confidence interval: 0.17 to 0.67; p = 0.002). The observed results were mainly attributable to the occurrence of new MI in the pre-catheterization period (0 deaths + 0 MIs in the immediate-intervention group vs. 1 death + 10 MIs in the delayed-intervention group). The rate of deaths, new MI, or recurrent ischemia was lower in the immediate-intervention group at both 30 days (6.8% vs. 26.7%; p < 0.001) and 1 year (15.4% vs. 33.1%; p < 0.001). CONCLUSIONS: Immediate invasive strategy in NSTEMI patients is associated with lower rates of death or new MI compared with the delayed invasive strategy at early and midterm follow-up, mainly due to a decrease in the risk of new MI in the pre-catheterization period. (Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients [RIDDLE-NSTEMI]; NCT02419833).

Timing of invasive strategy in NSTE-ACS patients and effect on clinical outcomes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Previous randomized controlled trials (RCTs) have produced conflicting results on the effects of early versus delayed invasive strategy in NSTE-ACS patients. OBJECTIVES: To perform up to date meta-analysis on the pooled data sample comparing early versus delayed invasive strategy, and to explore potential causes for the observed high statistical heterogeneity. METHODS: MEDLINE via Pubmed, Central, Google Scholar, Clinical Trials Registry, Current controlled study and ClinicalTrials.gov registry and relevant conference proceedings were searched. RCTs were included that directly compared early versus delayed invasive strategy and reported rates of death, new myocardial infarction (MI) and/or recurrent ischemia. RESULTS: 10 RCTs with 6089 patients were included. Time to coronary angiography varied from 0.5 to 24 h in the early and from 20.5 to 86 h in the delayed group. Meta-analysis showed no significant difference in mortality (OR = 0.83, 95%CI 0.64-1.08, P = 0.16), and similar new MI rates (OR = 1.02, 95%CI 0.63-1.64, P = 0.94). The rate of recurrent ischemia was reduced in patients undergoing early coronary angiography (OR = 0.56, 95%CI 0.40-0.79, P = 0.001). Subgroup analysis indicated that the rate of new MI tended to depend on the study-specific endpoint definition (p for difference between subgroups 0.11), while a meta-regression revealed association of new MI rates with the within-study delay to coronary angiography (p = 0.05). CONCLUSION: Early invasive strategy appears to reduce the occurrence of recurrent ischemia, but confers no mortality benefit. The true effect on the occurrence of new MI is obscured by the high between-study heterogeneity that stems mainly from non-uniform timing of early intervention and new MI definitions across the trials.

Coronary thrombi neovascularization in patients with ST-elevation myocardial infarction - clinical and angiographic implications.

INTRODUCTION: Coronary artery thrombosis in ST-elevation myocardial infarction (STEMI) is a dynamic process often preceded by episodes of silent plaque rupture and subocclusive thrombosis. Thrombus organization is achieved by ingrowth of endothelial and smooth muscle cells. Clinical significance and impact of thrombus neovascularization on primary percutaneous coronary intervention (pPCI) outcome remain unclear. Therefore we investigated composition and neovascularization of thrombi aspirated during pPCI and their association with clinical and angiographic parameters of STEMI patients. METHODS: Aspirated thrombi retrieved from 84 STEMI patients were classified as fresh (<1 day), lytic (1-5 days) or organized (>5 days). Thrombus neovascularization was evaluated immunohistochemically using CD34, CD31 and VEGF antibodies. CD34 and CD31 immunopositive (CD34/CD31+) cells were organized as single, clusters and microvessels. VEGF positivity was graded as low or high, based on thrombus surface immunopositive area. RESULTS: CD34/CD31+ cells were present in 67% of all aspirated thrombi. Thrombus CD34/CD31 positivity was associated with previous history of angina pectoris (χ(2)=6.142, p=0.013) and lower myocardial blush grade (MBG<3, χ(2)=12.602, p<0.001). Organization of CD34/CD31+ cells showed inverse association with the extent of VEGF positivity (χ(2)=10.607, p=0.005). Fresh thrombi were associated with shorter ischemic time (U=237.5, p=0.002) and MBG 3 (χ(2)=6.379, p=0.012). CONCLUSIONS: Older thrombus age and neovascularization are associated with suboptimal myocardial perfusion in STEMI patients. Thrombus VEGF expression is inversely associated with degree of CD34+ cell organization. Therefore, neovascularization of aspirated thrombi may indicate the duration of thrombosis, coronary microcirculation status and outcome in STEMI patients.